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Nail dystrophy

MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Synonyms: Dystrophic nails; Onychodystrophy
SNOMED CT: Dystrophia unguium (87065009); Onychodystrophy (87065009); Nail dystrophy (87065009); Dystrophic nail (87065009)
 
HPO: HP:0008404

Definition

Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate. [from HPO]

Conditions with this feature

Focal dermal hypoplasia
MedGen UID:
42055
Concept ID:
C0016395
Disease or Syndrome
Focal dermal hypoplasia is a multisystem disorder characterized primarily by involvement of the skin, skeletal system, eyes, and face. Skin manifestations present at birth include atrophic and hypoplastic areas of skin; cutis aplasia; fat nodules in the dermis manifesting as soft, yellow-pink cutaneous nodules; and pigmentary changes. Verrucoid papillomas of the skin and mucous membranes may appear later. The nails can be ridged, dysplastic, or hypoplastic; hair can be sparse or absent. Limb malformations include oligo-/syndactyly and split hand/foot. Developmental abnormalities of the eye can include anophthalmia/microphthalmia, iris and chorioretinal coloboma, and lacrimal duct abnormalities. Craniofacial findings can include facial asymmetry, notched alae nasi, cleft lip and palate, and pointed chin. Occasional findings include dental anomalies, abdominal wall defects, diaphragmatic hernia, and renal anomalies. Psychomotor development is usually normal; some individuals have cognitive impairment.
Hereditary insensitivity to pain with anhidrosis
MedGen UID:
6915
Concept ID:
C0020074
Disease or Syndrome
NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of NTRK1-CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.
Incontinentia pigmenti syndrome
MedGen UID:
7049
Concept ID:
C0021171
Disease or Syndrome
Incontinentia pigmenti (IP) is a disorder that affects the skin, hair, teeth, nails, eyes, and central nervous system; it occurs primarily in females and on occasion in males. Characteristic skin lesions evolve through four stages: I. Blistering (birth to age ~4 months). II. Wart-like rash (for several months). III. Swirling macular hyperpigmentation (age ~6 months into adulthood). IV. Linear hypopigmentation. Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Neovascularization of the retina, present in some individuals, predisposes to retinal detachment. Neurologic findings including seizures, intellectual disability, and developmental delays are occasionally seen.
Tangier disease
MedGen UID:
52644
Concept ID:
C0039292
Disease or Syndrome
Tangier disease is characterized by severe deficiency or absence of high-density lipoprotein (HDL) in the circulation resulting in tissue accumulation of cholesteryl esters throughout the body, particularly in the reticuloendothelial system. The major clinical signs of Tangier disease include hyperplastic yellow-orange tonsils, hepatosplenomegaly, and peripheral neuropathy, which may be either relapsing-remitting or chronic progressive in nature. Rarer complications may include corneal opacities that typically do not affect vision, premature atherosclerotic coronary artery disease occurring in the sixth and seventh decades of life (not usually before age 40 years), and mild hematologic manifestations, such as mild thrombocytopenia, reticulocytosis, stomatocytosis, or hemolytic anemia. The clinical expression of Tangier disease is variable, with some affected individuals only showing biochemical perturbations.
Werner syndrome
MedGen UID:
12147
Concept ID:
C0043119
Disease or Syndrome
Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Individuals with Werner syndrome develop normally until the end of the first decade. The first sign is the lack of a growth spurt during the early teen years. Early findings (usually observed in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. Myocardial infarction and cancer are the most common causes of death; the mean age of death in individuals with Werner syndrome is 54 years.
Epidermolysis bullosa simplex 1A, generalized severe
MedGen UID:
38194
Concept ID:
C0079295
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Recessive dystrophic epidermolysis bullosa
MedGen UID:
36311
Concept ID:
C0079474
Disease or Syndrome
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Junctional epidermolysis bullosa gravis of Herlitz
MedGen UID:
36328
Concept ID:
C0079683
Disease or Syndrome
Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures.
Polyglandular autoimmune syndrome, type 1
MedGen UID:
39125
Concept ID:
C0085859
Disease or Syndrome
Autoimmune polyglandular syndrome type I (APS1) is characterized by the presence of 2 of 3 major clinical symptoms: Addison disease, and/or hypoparathyroidism, and/or chronic mucocutaneous candidiasis (Neufeld et al., 1981). However, variable APS1 phenotypes have been observed, even among sibs. In addition, some patients may exhibit apparent isolated hypoparathyroidism, an early manifestation of APS1 with peak incidence at around age 5 years; over long-term follow-up, the development of additional features of APS1 may be observed (Cranston et al., 2022).
Hidrotic ectodermal dysplasia syndrome
MedGen UID:
56416
Concept ID:
C0162361
Disease or Syndrome
Hidrotic ectodermal dysplasia 2, or Clouston syndrome (referred to as HED2 throughout this GeneReview) is characterized by a triad of major clinical features including partial-to-complete alopecia, nail dystrophy, and palmoplantar hyperkeratosis. Sweating is preserved and there are usually no dental anomalies. Sparse scalp hair and dysplastic nails are seen early in life. In infancy, scalp hair is fine, sparse, and brittle. Progressive hair loss may lead to total alopecia by puberty. The nails may be milky white in early childhood; they gradually become dystrophic, thick, and distally separated from the nail bed. Palmoplantar keratoderma may develop during childhood and increases in severity with age. Associated features may include cutaneous hyperpigmentation (particularly over the joints) and finger clubbing. The clinical manifestations are highly variable even within the same family.
Oto-palato-digital syndrome, type I
MedGen UID:
78542
Concept ID:
C0265251
Disease or Syndrome
The X-linked otopalatodigital (X-OPD) spectrum disorders, characterized primarily by skeletal dysplasia, include the following: Otopalatodigital syndrome type 1 (OPD1). Otopalatodigital syndrome type 2 (OPD2). Frontometaphyseal dysplasia type 1 (FMD1). Melnick-Needles syndrome (MNS). Terminal osseous dysplasia with pigmentary skin defects (TODPD). In OPD1, most manifestations are present at birth; females can present with severity similar to affected males, although some have only mild manifestations. In OPD2, females are less severely affected than related affected males. Most males with OPD2 die during the first year of life, usually from thoracic hypoplasia resulting in pulmonary insufficiency. Males who live beyond the first year of life are usually developmentally delayed and require respiratory support and assistance with feeding. In FMD1, females are less severely affected than related affected males. Males do not experience a progressive skeletal dysplasia but may have joint contractures and hand and foot malformations. Progressive scoliosis is observed in both affected males and females. In MNS, wide phenotypic variability is observed; some individuals are diagnosed in adulthood, while others require respiratory support and have reduced longevity. MNS in males results in perinatal lethality in all recorded cases. TODPD, seen only in females, is characterized by a skeletal dysplasia that is most prominent in the digits, pigmentary defects of the skin, and recurrent digital fibromata.
Autosomal dominant keratitis-ichthyosis-hearing loss syndrome
MedGen UID:
120536
Concept ID:
C0265336
Disease or Syndrome
Keratitis-ichthyosis-deafness (KID) syndrome is a rare ectodermal dysplasia characterized by sensorineural hearing loss, photophobia and corneal vascularization, hyperkeratosis of the palms and soles, erythrokeratoderma, follicular hyperkeratosis, and recurrent bacterial and fungal infections. A subset of patients with KID may develop multiple cystic pilar tumors, which are prone to malignant transformation and metastasis (Nyquist et al., 2007). Vohwinkel syndrome (124500) is an allelic disorder involving congenital deafness with keratopachydermia and constrictions of fingers and toes. Another similar disorder caused by mutation in GJB2 is palmoplantar keratoderma with deafness (148350). Genetic Heterogeneity of Keratitis-Ichthyosis-Deafness Syndrome An autosomal recessive form of KID syndrome (KIDAR; 242150) is caused by mutation in the AP1B1 gene (600157) on chromosome 22q12.
Progressive recessive dystrophic epidermolysis bullosa
MedGen UID:
78666
Concept ID:
C0268368
Congenital Abnormality
Dominant dystrophic epidermolysis bullosa with absence of skin
MedGen UID:
82797
Concept ID:
C0268371
Congenital Abnormality
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Junctional epidermolysis bullosa, non-Herlitz type
MedGen UID:
82798
Concept ID:
C0268374
Disease or Syndrome
Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures.
Cronkhite-Canada syndrome
MedGen UID:
129128
Concept ID:
C0282207
Disease or Syndrome
Cronkhite-Canada syndrome is characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, skin hyperpigmentation, and diarrhea. It is associated with high morbidity (summary by Sweetser et al., 2012).
Acrodermatitis continua suppurativa of Hallopeau
MedGen UID:
581114
Concept ID:
C0392439
Disease or Syndrome
A rare, genetic, chronic, recurrent, slowly progressive, epidermal disease characterized by small, sterile, pustular eruptions, involving the nails and surrounding skin of the fingers and/or toes, which coalesce and burst, leaving erythematous, atrophic skin where new pustules develop. Onychodystrophy is frequently associated and anonychia and osteolysis are reported in severe cases. Local expansion (to involve the hands, forearms and/or feet) and involvement of mucosal surfaces (e.g. conjunctiva, tongue, urethra) may be observed.
Basan syndrome
MedGen UID:
140808
Concept ID:
C0406707
Disease or Syndrome
Complete congenital absence of dermatoglyphs is a rare syndrome characterized by autosomal dominant inheritance of the lack of ridges on palms and soles, neonatal acral blisters and facial milia, adult traumatic blistering and fissuring, absent or reduced sweating of palms and soles, and contracture of digits. Additional features may include single palmar transverse crease, palmoplantar keratoderma, and nail grooving (summary by Limova et al., 1993).
Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome
MedGen UID:
98032
Concept ID:
C0406709
Disease or Syndrome
The TP63-related disorders comprise six overlapping phenotypes: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome). Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3). Limb-mammary syndrome. Split-hand/foot malformation type 4 (SHFM4). Isolated cleft lip/cleft palate (orofacial cleft 8). Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling.
Keratoderma with scleroatrophy of the extremities
MedGen UID:
98360
Concept ID:
C0406767
Congenital Abnormality
Huriez syndrome (HRZ) is characterized by the triad of congenital scleroatrophy of the distal extremities, palmoplantar keratoderma, and hypoplastic nail changes. The development of aggressive squamous cell carcinoma (SCC) in areas of affected skin is a distinctive feature of the syndrome, occurring in approximately 15% of patients. HRZ-associated SCC shows early onset, mostly in the third to fourth decades of life, and early metastasis formation (summary by Lee et al., 2000). See also 610644 for description of a disorder resembling Huriez syndrome, involving palmoplantar hyperkeratosis and squamous cell carcinoma in association with SRY (480000)-negative female-to-male XX sex reversal, caused by mutation in the RSPO1 gene (609595).
Dermatopathia pigmentosa reticularis
MedGen UID:
98037
Concept ID:
C0406778
Congenital Abnormality
Dermatopathia pigmentosa reticularis (DPR) is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. Variable features include adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis (Heimer et al., 1992).
Epidermolysis bullosa simplex with mottled pigmentation
MedGen UID:
140934
Concept ID:
C0432316
Congenital Abnormality
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Pretibial dystrophic epidermolysis bullosa
MedGen UID:
98154
Concept ID:
C0432321
Congenital Abnormality
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Generalized dominant dystrophic epidermolysis bullosa
MedGen UID:
140935
Concept ID:
C0432322
Congenital Abnormality
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Beaded hair
MedGen UID:
108185
Concept ID:
C0546966
Congenital Abnormality
Individuals with monilethrix have normal hair at birth, but within the first few months of life develop fragile, brittle hair that tends to fracture and produce varying degrees of dystrophic alopecia. In the mildest forms, only the occipital regions of the scalp are involved; however, in severe forms the eyebrows, eyelashes, and secondary sexual hair may also be involved. Follicular hyperkeratosis with predilection for the scalp, nape of neck, and extensor surfaces of the upper arm and thighs is also a characteristic finding in these patients. Light microscopic examination is diagnostic and reveals elliptical nodes of normal thickness and intermittent constrictions (internodes) at which the hair easily breaks. There may be spontaneous improvement with time, especially during puberty and pregnancy, but the condition never resolves completely (summary by Zlotogorski et al., 2006). An autosomal recessive form of monilethrix-like congenital hypotrichosis (see 607903) is caused by mutation in the DSG4 gene (607892). The clinical picture of autosomal recessive monilethrix is more severe than the dominant form, with more extensive alopecia of the scalp, body, and limbs, and a papular rash involving the extremities and periumbilical region (Zlotogorski et al., 2006). The term monilethrix derives from the Latin word for necklace and the Greek for hair (Schweizer, 2006).
Sabinas brittle hair syndrome
MedGen UID:
163238
Concept ID:
C0796271
Disease or Syndrome
The principal features of Sabinas brittle hair syndrome, a form of nonphotosensitive trichothiodystrophy (TTDN; see 234050), include congenital hypotrichosis, mild to moderate onychodysplasia, varying mental retardation, and sterility. Ocular dysplasias are sometimes present and dentition is normal (Howell et al., 1980).
Dyskeratosis congenita, X-linked
MedGen UID:
216941
Concept ID:
C1148551
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Hereditary mucoepithelial dysplasia
MedGen UID:
220887
Concept ID:
C1274795
Congenital Abnormality
Hereditary mucoepithelial dysplasia (HMD) is a rare autosomal dominant genodermatosis characterized by onset in infancy of a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Patients develop cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses (Witkop et al., 1982). Although 1 family was reported to have progressive severe interstitial lung disease (Witkop et al., 1979), this feature has not been reported in other families and is not considered a criterion for diagnosis. However, the clinical triad of nonscarring alopecia, well-demarcated fiery red mucosa, and psoriasiform perineal involvement has been consistently observed (review by Boralevi et al., 2005).
Epidermolysis bullosa pruriginosa
MedGen UID:
266151
Concept ID:
C1275114
Disease or Syndrome
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Trichothiodystrophy 4, nonphotosensitive
MedGen UID:
272036
Concept ID:
C1313961
Disease or Syndrome
Trichothiodystrophy is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder (summary by Faghri et al., 2008). Sabinas brittle hair syndrome (211390) is another form of nonphotosensitive TTD. For a discussion of genetic heterogeneity of trichothiodystrophy, see 601675.
Revesz syndrome
MedGen UID:
231230
Concept ID:
C1327916
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Laryngo-onycho-cutaneous syndrome
MedGen UID:
272227
Concept ID:
C1328355
Disease or Syndrome
Junctional epidermolysis bullosa 2C (JEB2C), also known as laryngoonychocutaneous syndrome (LOCS), is an autosomal recessive disorder characterized by skin erosions, nail dystrophy, dental anomalies, and excessive vascular granulation tissue of the conjunctiva and larynx. Onset is characterized by a hoarse cry soon after birth. Beginning in infancy, chronic skin ulcers and conjunctival lesions appear. Patients may die in childhood secondary to acute or chronic respiratory obstruction. Long-term survivors have visual loss and often require tracheostomy (McLean et al., 2003). For a discussion of genetic heterogeneity of the subtypes of JEB, see JEB1A (226650). Reviews Has et al. (2020) reviewed the clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors, and natural history of epidermolysis bullosa.
Pachyonychia congenita 1
MedGen UID:
353335
Concept ID:
C1706595
Disease or Syndrome
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, painful palmoplantar keratoderma and blistering, oral leukokeratosis, pilosebaceous cysts (including steatocystoma and vellus hair cysts), palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities.
Pachyonychia congenita 2
MedGen UID:
314107
Concept ID:
C1721007
Disease or Syndrome
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, painful palmoplantar keratoderma and blistering, oral leukokeratosis, pilosebaceous cysts (including steatocystoma and vellus hair cysts), palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities.
Rapp-Hodgkin ectodermal dysplasia syndrome
MedGen UID:
315656
Concept ID:
C1785148
Disease or Syndrome
The TP63-related disorders comprise six overlapping phenotypes: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome). Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3). Limb-mammary syndrome. Split-hand/foot malformation type 4 (SHFM4). Isolated cleft lip/cleft palate (orofacial cleft 8). Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling.
Naxos disease
MedGen UID:
321991
Concept ID:
C1832600
Disease or Syndrome
Naxos disease (NXD) is characterized by arrhythmogenic right ventricular cardiomyopathy associated with abnormalities of the skin, hair, and nails. The ectodermal features are evident from birth or early childhood, whereas the cardiac symptoms develop in young adulthood or later. Clinical variability of ectodermal features has been observed, with hair anomalies ranging from woolly hair to alopecia, and skin abnormalities ranging from mild focal palmoplantar keratoderma to generalized skin fragility or even lethal neonatal epidermolysis bullosa (Protonotarios et al., 1986; Cabral et al., 2010; Pigors et al., 2011; Erken et al., 2011; Sen-Chowdhry and McKenna, 2014). Another syndrome involving cardiomyopathy, woolly hair, and keratoderma (DCWHK; 605676) is caused by mutation in the desmoplakin gene (DSP; 125647). Also see 610476 for a similar disorder caused by homozygous mutation in the DSC2 gene (125645).
Ayme-Gripp syndrome
MedGen UID:
371416
Concept ID:
C1832812
Disease or Syndrome
Aymé-Gripp syndrome is classically defined as the triad of bilateral early cataracts, sensorineural hearing loss, and characteristic facial features in combination with neurodevelopmental abnormalities. The facial features are often described as "Down syndrome-like" and include brachycephaly, flat facial appearance, short nose, long philtrum, narrow mouth, and low-set and posteriorly rotated ears. Hearing loss is often congenital. Other features may include postnatal short stature, seizure disorder, nonspecific brain abnormalities on head imaging, skeletal abnormalities, and joint limitations. A subset of individuals have been found to have pericarditis or pericardial effusion during the neonatal or infantile period. All affected individuals have had developmental delay, but the degree of cognitive impairment is extremely variable. Other features including gastrointestinal and endocrine abnormalities, ectodermal dysplasia (i.e., nail dystrophy and mammary gland hypoplasia), dental anomalies, and chronic glomerulopathy with proteinuria have been reported in rare affected individuals.
Epidermolysis bullosa simplex 7, with nephropathy and deafness
MedGen UID:
323004
Concept ID:
C1836823
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Split hand-foot malformation 3
MedGen UID:
325070
Concept ID:
C1838652
Disease or Syndrome
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM3 have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600).
Peeling skin syndrome 1
MedGen UID:
336530
Concept ID:
C1849193
Disease or Syndrome
A group of rare autosomal recessive forms of ichthyosis with clinical characteristics of superficial, asymptomatic, spontaneous peeling of the skin and histologically by a shedding of the outer layers of the epidermis. Presents with either an acral or a generalised distribution.
Transient bullous dermolysis of the newborn
MedGen UID:
343607
Concept ID:
C1851573
Disease or Syndrome
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma
MedGen UID:
340124
Concept ID:
C1854063
Disease or Syndrome
Dilated cardiomyopathy with woolly hair and keratoderma (DCWHK) is characterized by the presence of woolly or sparse hair from birth. Some patients exhibit fragile skin with blisters/erosions after minor mechanical trauma, with hyperkeratosis and epidermolytic keratoderma developing in early childhood. Cardiomyopathy may become apparent in the first decade of life, and early death due to heart failure has been reported, but patients may remain asymptomatic into the fourth decade of life. Some patients exhibit an arrhythmogenic form of cardiomyopathy, with sudden death in early adulthood (Carvajal-Huerta, 1998; Whittock et al., 2002; Alcalai et al., 2003; Uzumcu et al., 2006). Another syndrome involving cardiomyopathy, woolly hair, and keratoderma (Naxos disease; 601214) is caused by mutation in the plakoglobin gene (JUP; 173325). Also see 610476 for a similar disorder caused by homozygous mutation in the DSC2 gene (125645). Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis (DCWHKTA; 615821) is caused by heterozygous mutation in DSP. An isolated form of striated PPK (PPKS2; 612908) is also caused by heterozygous mutation in DSP. Reviews In a review of cardiocutaneous syndromes and arrhythmogenic cardiomyopathy, Sen-Chowdhry and McKenna (2014) stated that although the cardiac component of Carvajal syndrome was originally considered dilated cardiomyopathy, many of its features resemble those of arrhythmogenic cardiomyopathy (see 607450). In addition, they noted that different disease subtypes have been found to coexist within the same kindred, suggesting a role for modifier genes and/or environmental influences.
SchC6pf-Schulz-Passarge syndrome
MedGen UID:
347366
Concept ID:
C1857069
Disease or Syndrome
Schopf-Schulz-Passarge syndrome (SSPS) is an autosomal recessive disorder characterized by a constellation of multiple eyelid cysts, hypodontia, hypotrichosis, palmoplantar hyperkeratosis, and onychodystrophy (summary by Mallaiah and Dickinson, 2001).
Dyskeratosis congenita, autosomal recessive 1
MedGen UID:
341705
Concept ID:
C1857144
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Epidermolysis bullosa simplex due to plakophilin deficiency
MedGen UID:
388032
Concept ID:
C1858302
Disease or Syndrome
Ectodermal dysplasia/skin fragility syndrome (EDSFS) is an autosomal recessive genodermatosis characterized by widespread skin fragility, alopecia, nail dystrophy, and focal keratoderma with painful fissures. Hypohidrosis and cheilitis are sometimes present (summary by Ersoy-Evans et al., 2006).
Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3
MedGen UID:
347666
Concept ID:
C1858562
Disease or Syndrome
The TP63-related disorders comprise six overlapping phenotypes: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome). Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3). Limb-mammary syndrome. Split-hand/foot malformation type 4 (SHFM4). Isolated cleft lip/cleft palate (orofacial cleft 8). Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling.
Poikiloderma with neutropenia
MedGen UID:
388129
Concept ID:
C1858723
Disease or Syndrome
Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers.
Autosomal recessive palmoplantar keratoderma and congenital alopecia
MedGen UID:
347851
Concept ID:
C1859316
Disease or Syndrome
Palmoplantar keratoderma and congenital alopecia-2 (PPKCA2) is an autosomal recessive disorder characterized by congenital alopecia and progressive hyperkeratosis resulting in sclerodactyly, severe contractures and tapering of the digits, and pseudoainhum formation. Nail changes occur in some patients (Castori et al., 2010). Also see PPKCA1 (104100), a less severe, autosomal dominant disorder.
Cooks syndrome
MedGen UID:
354848
Concept ID:
C1862841
Disease or Syndrome
Familial anonychia/onychodystrophy with hypoplasia or absence of distal phalanges (ODP) is a rare disorder characterized by onychodystrophy, anonychia, brachydactyly of the fifth finger, and digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet. Generally the nails of the first to third digits are progressively deformed with total anonychia in the last 2 digits and in all toes (summary by Genzer-Nir et al., 2010). A syndrome has been described in which affected females display juvenile hypertrophy of the breast (JHB; 113670) in association with ODP, whereas males have only ODP (mammary-digital-nail syndrome; 613689).
Pure hair and nail ectodermal dysplasia
MedGen UID:
400883
Concept ID:
C1865951
Disease or Syndrome
Pure hair and nail ectodermal dysplasia is characterised by the association of onychodystrophy and severe hypotrichosis, which is mainly limited to the scalp but may also affect the eyelashes and eyebrows. Less than 20 cases have been reported so far. The mode of transmission is autosomal dominant.
Odonto-tricho-ungual-digito-palmar syndrome
MedGen UID:
400891
Concept ID:
C1865998
Disease or Syndrome
This syndrome has characteristics of neonatal teeth, trichodystrophy and malformations of the hands and feet. To date, it has been reported in 21 patients and is transmitted as an autosomal dominant trait.
Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome
MedGen UID:
356430
Concept ID:
C1866029
Disease or Syndrome
An inherited epidermal disorder with characteristics of palmoplantar keratoderma, linear hyperkeratotic papules on the flexural side of large joints (cord-like distribution around wrists, in antecubital and popliteal folds), hyperkeratotic plaques (on neck, axillae, elbows, wrists, and knees), mild ichthyosiform scaling, and sclerotic constrictions around fingers that present flexural deformities. The disease is caused by homozygous mutation in the POMP gene.
T-cell immunodeficiency, congenital alopecia, and nail dystrophy
MedGen UID:
355713
Concept ID:
C1866426
Disease or Syndrome
T-cell immunodeficiency, congenital alopecia, and nail dystrophy (TIDAND) is an autosomal recessive primary immunodeficiency characterized by congenital thymic aplasia and severe T-cell immunodeficiency apparent at birth or soon thereafter. Affected individuals tend to have recurrent infections, oral candidiasis, and failure to thrive. Immunologic investigations show decreased numbers of T cells with poor proliferative response to phytohemagglutinin (PHA) and variable hypogammaglobulinemia. The phenotype is consistent with a T-/B+/NK+ form of severe combined immunodeficiency (SCID; see, e.g., 102700). Patients with FOXN1 mutations do not respond well to hematopoietic stem cell transplantation, as it is not curative; thymic transplantation offers a potential cure (Chou et al., 2014).
Trichothiodystrophy 1, photosensitive
MedGen UID:
355730
Concept ID:
C1866504
Disease or Syndrome
About half of all people with trichothiodystrophy have a photosensitive form of the disorder, which causes them to be extremely sensitive to ultraviolet (UV) rays from sunlight. They develop a severe sunburn after spending just a few minutes in the sun. However, for reasons that are unclear, they do not develop other sun-related problems such as excessive freckling of the skin or an increased risk of skin cancer. Many people with trichothiodystrophy report that they do not sweat.\n\nTrichothiodystrophy is also associated with recurrent infections, particularly respiratory infections, which can be life-threatening. People with trichothiodystrophy may have abnormal red blood cells, including red blood cells that are smaller than normal. They may also have elevated levels of a type of hemoglobin called A2, which is a protein found in red blood cells. Other features of trichothiodystrophy can include dry, scaly skin (ichthyosis); abnormalities of the fingernails and toenails; clouding of the lens in both eyes from birth (congenital cataracts); poor coordination; and skeletal abnormalities including degeneration of both hips at an early age.\n\nIntellectual disability and delayed development are common in people with trichothiodystrophy, although most affected individuals are highly social with an outgoing and engaging personality. Some people with trichothiodystrophy have brain abnormalities that can be seen with imaging tests. A common neurological feature of this disorder is impaired myelin production (dysmyelination). Myelin is a fatty substance that insulates nerve cells and promotes the rapid transmission of nerve impulses.\n\nMothers of children with trichothiodystrophy may experience problems during pregnancy including pregnancy-induced high blood pressure (preeclampsia) and a related condition called HELLP syndrome that can damage the liver. Babies with trichothiodystrophy are at increased risk of premature birth, low birth weight, and slow growth. Most children with trichothiodystrophy have short stature compared to others their age. \n\nThe signs and symptoms of trichothiodystrophy vary widely. Mild cases may involve only the hair. More severe cases also cause delayed development, significant intellectual disability, and recurrent infections; severely affected individuals may survive only into infancy or early childhood.\n\nIn people with trichothiodystrophy, tests show that the hair is lacking sulfur-containing proteins that normally gives hair its strength. A cross section of a cut hair shows alternating light and dark banding that has been described as a "tiger tail."\n\nTrichothiodystrophy, commonly called TTD, is a rare inherited condition that affects many parts of the body. The hallmark of this condition is hair that is sparse and easily broken. 
Porokeratosis 3, disseminated superficial actinic type
MedGen UID:
401352
Concept ID:
C1867981
Disease or Syndrome
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Mutations in the MVK gene have been found to cause multiple types of porokeratosis, which have been described as disseminated superficial actinic porokeratosis (DSAP), nonactinic disseminated superficial porokeratosis (DSP), porokeratosis of Mibelli, giant plaque of porokeratosis ptychotropica, hyperkeratotic porokeratosis, and linear porokeratosis. The preferred title of this entry was formerly 'Porokeratosis 3, Disseminated Superficial Actinic Type; POROK3.' Disseminated superficial actinic porokeratosis is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012). For a discussion of genetic heterogeneity of porokeratosis, see 175800.
Epidermolysis bullosa, junctional 4, intermediate
MedGen UID:
382015
Concept ID:
C2608084
Disease or Syndrome
Autosomal dominant deafness - onychodystrophy syndrome
MedGen UID:
382676
Concept ID:
C2675730
Disease or Syndrome
The DDOD syndrome is characterized by autosomal dominant inheritance of congenital deafness and onychodystrophy. Conical, hypoplastic teeth is also a feature (Robinson et al., 1962). See also DOOR syndrome (220500), an autosomal recessive disorder, which includes congenital deafness, onychodystrophy, osteodystrophy, and mental retardation.
Keratosis follicularis spinulosa decalvans, autosomal dominant
MedGen UID:
412573
Concept ID:
C2748527
Disease or Syndrome
Keratosis follicularis spinulosa decalvans (KFSD) is an uncommon genodermatosis characterized by follicular hyperkeratosis, progressive cicatricial alopecia, and photophobia. Most reported cases show X-linked inheritance (KFSDX; 308800) (Castori et al., 2009).
Epidermolysis bullosa simplex 5B, with muscular dystrophy
MedGen UID:
418981
Concept ID:
C2931072
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Palmoplantar keratoderma i, striate, focal, or diffuse
MedGen UID:
419717
Concept ID:
C2931122
Disease or Syndrome
Striate palmoplantar keratoderma belongs to a group of skin diseases in which there is thickening of the skin on the palms and soles. The striate form is characterized by longitudinal hyperkeratotic lesions extending the length of each finger to the palm, and hyperkeratotic lesions are restricted to regions of the body where pressure and abrasion are greatest (summary by Hunt et al., 2001). Patients with diffuse or focal forms of keratoderma associated with mutation in the DSG1 gene have also been reported (Keren et al., 2005; Milingou et al., 2006). Genetic Heterogeneity of Keratosis Palmoplantaris Striata Type II PPKS (PPKS2; 612908) is caused by mutation in the DSP gene (125647) on chromosome 6. Type III PPKS (PPKS3; 607654) is caused by mutation in the keratin-1 gene (KRT1; 139350) on chromosome 12q. For a general phenotypic description and a discussion of genetic heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK (144200). Nitoiu et al. (2014) reviewed desmosome biology in cardiocutaneous syndromes and inherited skin disease, including discussion of the involvement of the DSG1 and DSP genes.
Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome
MedGen UID:
461281
Concept ID:
C3149931
Disease or Syndrome
Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome is characterised by sex reversal in males with a 46, XX (SRY-negative) karyotype, palmoplantar hyperkeratosis and a predisposition to squamous cell carcinoma. To date, five cases (four of whom were brothers) have been described. The aetiology is unknown.
Mammary-digital-nail syndrome
MedGen UID:
462296
Concept ID:
C3150946
Disease or Syndrome
A syndromic limb malformation characterized by congenital onychodystrophy/anonychia, brachydactyly of the fifth finger, digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet in association with juvenile hypertrophy of the breast with gigantomastia in peripubertal females.
Neuropathy, hereditary sensory, type 1D
MedGen UID:
462322
Concept ID:
C3150972
Disease or Syndrome
Spastic paraplegia 3A (SPG3A; also known as ATL1-HSP) is characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs. Compared to other forms of autosomal dominant hereditary spastic paraplegia (HSP), in which diminished vibration sense (caused by degeneration of the corticospinal tracts and dorsal columns) and urinary bladder hyperactivity are present in all affected individuals, these findings occur in a minority of individuals with SPG3A. The average age of onset is four years. More than 80% of reported individuals manifest spastic gait before the end of the first decade of life. Most persons with early-onset ATL1-HSP have a "pure" ("uncomplicated") HSP; however, complicated HSP with axonal motor neuropathy and/or distal amyotrophy with lower motor neuron involvement (Silver syndrome phenotype) has been observed. The rate of progression in ATL1-HSP is slow, and wheelchair dependency or need for a walking aid (cane, walker, or wheelchair) is relatively rare.
Dyskeratosis congenita, autosomal recessive 2
MedGen UID:
462791
Concept ID:
C3151441
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Dyskeratosis congenita, autosomal recessive 3
MedGen UID:
462792
Concept ID:
C3151442
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Dyskeratosis congenita, autosomal dominant 2
MedGen UID:
462793
Concept ID:
C3151443
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Dyskeratosis congenita, autosomal dominant 3
MedGen UID:
462795
Concept ID:
C3151445
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Nestor-Guillermo progeria syndrome
MedGen UID:
462796
Concept ID:
C3151446
Disease or Syndrome
Nestor-Guillermo progeria syndrome (NGPS) is an autosomal recessive disorder characterized by lipoatrophy, osteoporosis, and very severe osteolysis. Patients have no cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia, but suffer profound skeletal abnormalities that affect their quality of life. Onset is after 2 years of age, and lifespan is relatively long (summary by Cabanillas et al., 2011).
Syndromic X-linked intellectual disability Nascimento type
MedGen UID:
477095
Concept ID:
C3275464
Disease or Syndrome
The Nascimento type of X-linked syndromic intellectual developmental disorder (MRXSN) is characterized by dysmorphic features, including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, abnormal hair whorls, micropenis, and onychodystrophy. Female carriers have normal cognition, but may show subtle facial features (summary by Budny et al., 2010).
Nonsyndromic congenital nail disorder 6
MedGen UID:
477175
Concept ID:
C3275544
Disease or Syndrome
Congenital absence of the nails is a rare condition. Some pedigrees display complete congenital absence of the nails (see, e.g., NDNC4, 206800), whereas in other pedigrees there is only partial congenital anonychia, with the thumbs and great toes most severely affected and progressively less severe changes in the more lateral digits (summary by Charteris, 1918). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-6 (NDNC6). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Chromosome 17q12 deletion syndrome
MedGen UID:
482768
Concept ID:
C3281138
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
MedGen UID:
482833
Concept ID:
C3281203
Neoplastic Process
Patients with familial cutaneous telangiectasia and cancer syndrome (FCTCS) develop cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well (Tanaka et al., 2012).
Linear skin defects with multiple congenital anomalies 2
MedGen UID:
763835
Concept ID:
C3550921
Disease or Syndrome
Microphthalmia with linear skin defects (MLS) syndrome is characterized by unilateral or bilateral microphthalmia and/or anophthalmia and linear skin defects, usually involving the face and neck, which are present at birth and heal with age, leaving minimal residual scarring. Other findings can include a wide variety of other ocular abnormalities (e.g., corneal anomalies, orbital cysts, cataracts), central nervous system involvement (e.g., structural anomalies, developmental delay, infantile seizures), cardiac concerns (e.g., hypertrophic or oncocytic cardiomyopathy, atrial or ventricular septal defects, arrhythmias), short stature, diaphragmatic hernia, nail dystrophy, hearing impairment, and genitourinary malformations. Inter- and intrafamilial variability is described.
Ectodermal dysplasia 9, hair/nail type
MedGen UID:
767041
Concept ID:
C3554127
Disease or Syndrome
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia) (summary by Lin et al., 2012).
Dyskeratosis congenita, autosomal recessive 5
MedGen UID:
767570
Concept ID:
C3554656
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Pachyonychia congenita 3
MedGen UID:
811523
Concept ID:
C3714948
Disease or Syndrome
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, painful palmoplantar keratoderma and blistering, oral leukokeratosis, pilosebaceous cysts (including steatocystoma and vellus hair cysts), palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities.
Pachyonychia congenita 4
MedGen UID:
811524
Concept ID:
C3714949
Disease or Syndrome
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, painful palmoplantar keratoderma and blistering, oral leukokeratosis, pilosebaceous cysts (including steatocystoma and vellus hair cysts), palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities.
Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome
MedGen UID:
815206
Concept ID:
C3808876
Neoplastic Process
Multiple self-healing palmoplantar carcinoma (MSPC) is characterized by recurrent keratoacanthomas in palmoplantar skin as well as in conjunctival and corneal epithelia. In addition, patients experience a high susceptibility to malignant squamous cell carcinoma (summary by Zhong et al., 2016).
Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency
MedGen UID:
815800
Concept ID:
C3809470
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Keratosis follicularis spinulosa decalvans, X-linked
MedGen UID:
854384
Concept ID:
C3887525
Congenital Abnormality
Keratosis follicularis spinulosa decalvans is an uncommon genodermatosis chiefly characterized by widespread keratosis pilaris, progressive cicatricial alopecia of the scalp, eyebrows, and eyelashes, and an excess of affected males. Photophobia, blepharitis/conjunctivitis, and corneal dystrophy are characteristic ancillary findings. It is most often inherited as an X-linked trait (summary by Castori et al., 2009). Autosomal dominant inheritance has also been reported (KFSD; 612843). The term 'cum ophiasi' means 'with ophiasis,' i.e., baldness in 1 or more winding streaks about the head, which comes from the Greek for snake. Decalvans refers to the loss of hair.
Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis
MedGen UID:
862830
Concept ID:
C4014393
Disease or Syndrome
Keratoderma with woolly hair is a group of related conditions that affect the skin and hair and in many cases increase the risk of potentially life-threatening heart problems. People with these conditions have hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.\n\nKeratoderma with woolly hair comprises several related conditions with overlapping signs and symptoms. Researchers have recently proposed classifying keratoderma with woolly hair into four types, based on the underlying genetic cause. Type I, also known as Naxos disease, is characterized by palmoplantar keratoderma, woolly hair, and a form of cardiomyopathy called arrhythmogenic right ventricular cardiomyopathy (ARVC). Type II, also known as Carvajal syndrome, has hair and skin abnormalities similar to type I but features a different form of cardiomyopathy, called dilated left ventricular cardiomyopathy. Type III also has signs and symptoms similar to those of type I, including ARVC, although the hair and skin abnormalities are often milder. Type IV is characterized by palmoplantar keratoderma and woolly and sparse hair, as well as abnormal fingernails and toenails. Type IV does not appear to cause cardiomyopathy.\n\nCardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.
Polyglucosan body myopathy type 1
MedGen UID:
863042
Concept ID:
C4014605
Disease or Syndrome
Polyglucosan body myopathy-1 (PGBM1) is an autosomal recessive disorder characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood (summary by Boisson et al., 2012 and Nilsson et al., 2013). Genetic Heterogeneity of Polyglucosan Body Myopathy See also PGBM2 (616199), caused by mutation in the GYG1 gene (603942) on chromosome 3q24.
STING-associated vasculopathy with onset in infancy
MedGen UID:
863159
Concept ID:
C4014722
Disease or Syndrome
STING-associated vasculopathy with onset in infancy is an autoinflammatory vasculopathy causing severe skin lesions, particularly affecting the face, ears, nose, and digits, and resulting in ulceration, eschar formation, necrosis, and, in some cases, amputation. Many patients have interstitial lung disease. Tissue biopsy and laboratory findings show a hyperinflammatory state, with evidence of increased beta-interferon (IFNB1; 147640) signaling (summary by Liu et al., 2014).
Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome
MedGen UID:
863424
Concept ID:
C4014987
Disease or Syndrome
A rare genetic ectodermal dysplasia syndrome characterized by short stature, nail dystrophy and/or nail loss, oral mucosa and/or tongue hyperpigmentation, dentition abnormalities (delayed teeth eruption, hypodontia, enamel hypoplasia), keratoderma on the margins of the palms and soles and focal hyperkeratosis on the dorsum of the hands and feet. Additionally, dysphagia with esophageal strictures, sensorineural deafness, bronchial asthma and severe iron-deficiency anemia have also been observed.
Psoriasis 15, pustular, susceptibility to
MedGen UID:
863672
Concept ID:
C4015235
Finding
While many affected individuals have features only of GPP (called GPP alone), some develop features of another skin condition called psoriasis vulgaris (PV), either before or after GPP appears. PV, the most common form of psoriasis, is characterized by red, scaly patches of skin (plaques) on parts of the body.\n\nGeneralized pustular psoriasis (GPP) is a severe form of a skin disorder called psoriasis. GPP and other forms of psoriasis are caused by abnormal inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, when inflammation is abnormal and uncontrolled, it can damage the body's tissues and organs. Individuals with GPP have repeated episodes in which large areas of skin become red and inflamed and develop small pus-filled blisters (pustules). The skin problems can be accompanied by fever, extreme tiredness (fatigue), muscle weakness, an increased number of white blood cells, and other signs of inflammation throughout the body (systemic inflammation). The inflammation problems subside and reappear often. Episodes can be triggered by infection, exposure to or withdrawal from certain medications, menstruation, or pregnancy, although the trigger is often unknown. GPP can be life-threatening if not treated.
Dyskeratosis congenita, autosomal dominant 6
MedGen UID:
904824
Concept ID:
C4225284
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Epidermolysis bullosa simplex with nail dystrophy
MedGen UID:
906476
Concept ID:
C4225309
Disease or Syndrome
Autosomal recessive generalized intermediate epidermolysis bullosa simplex 5D (EBS5D) is characterized by generalized skin blistering that heals with scarring and hyperpigmentation. Nail dystrophy is severe. Mucous membranes, heart, and muscle are spared (Gostynska et al., 2015). For a discussion of genetic heterogeneity of the subtypes of EBS, see EBS1A (131760).
Dyskeratosis congenita, autosomal recessive 6
MedGen UID:
905452
Concept ID:
C4225356
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Peeling skin syndrome 4
MedGen UID:
895692
Concept ID:
C4225407
Disease or Syndrome
Any peeling skin syndrome in which the cause of the disease is a mutation in the CSTA gene.
Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type
MedGen UID:
934583
Concept ID:
C4310616
Disease or Syndrome
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).
Bone marrow failure syndrome 3
MedGen UID:
934711
Concept ID:
C4310744
Disease or Syndrome
Bone marrow failure syndrome-3 is an autosomal recessive disorder characterized by onset of pancytopenia in early childhood. Patients may have additional variable nonspecific somatic abnormalities, including poor growth, microcephaly, and skin anomalies (summary by Tummala et al., 2016). BMFS3 has a distinct phenotype and may include features that overlap with Shwachman-Diamond syndrome (SDS1; 260400), such as pancreatic insufficiency and short stature, and with dyskeratosis congenita (see, e.g., DKCA1, 127550), such as dental and hair abnormalities and shortened telomeres. In addition, some patients may have joint and skeletal abnormalities, impaired development, and retinal dysplasia (summary by D'Amours et al., 2018). For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675).
Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
MedGen UID:
1388385
Concept ID:
C4518785
Disease or Syndrome
Junctional epidermolysis bullosa-7 with interstitial lung disease and nephrotic syndrome (JEB7), also known as ILNEB, is an autosomal recessive multiorgan disorder that includes congenital interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the lethal course of the disease (summary by Has et al., 2012).
Autosomal recessive congenital ichthyosis 1
MedGen UID:
1635401
Concept ID:
C4551630
Disease or Syndrome
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.
Dyskeratosis congenita, autosomal dominant 1
MedGen UID:
1645250
Concept ID:
C4551974
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Cerebroretinal microangiopathy with calcifications and cysts 1
MedGen UID:
1636142
Concept ID:
C4552029
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Angioma serpiginosum, X-linked
MedGen UID:
1648301
Concept ID:
C4721404
Disease or Syndrome
Angioma serpiginosum (AS) is a rare benign congenital skin disorder characterized by nonpurpuric red punctate lesions seen histologically as capillary ectasias in the superficial papillary dermis. The lesions often follow Blaschko lines and are most commonly found in females (90%) (Blinkenberg et al., 2007). See 106050 for additional phenotypic information and possible autosomal dominant inheritance or cutaneous somatic mosaicism (Chen et al., 2006; Blinkenberg et al., 2007).
Bone marrow failure syndrome 5
MedGen UID:
1648380
Concept ID:
C4748488
Disease or Syndrome
Bone marrow failure syndrome-5 (BMFS5) is a hematologic disorder characterized by infantile onset of severe red cell anemia requiring transfusion. Additional features include hypogammaglobulinemia, poor growth with microcephaly, developmental delay, and seizures (summary by Toki et al., 2018) For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675).
Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma
MedGen UID:
1678330
Concept ID:
C5193062
Disease or Syndrome
CAPOK syndrome (CAPOK) is characterized by onset of symptoms in the first year of life, with the development of progressive alopecia, hypo- and hyperpigmented macular skin lesions, palmoplantar keratoderma, and nail dystrophy. Beginning in the third decade of life, patients develop recurrent squamous cell carcinomas. Some patients may have brittle teeth resulting in tooth loss, and multinodular goiter has been observed (Courcet et al., 2015).
Rothmund-Thomson syndrome type 2
MedGen UID:
1684753
Concept ID:
C5203410
Disease or Syndrome
Rothmund-Thomson syndrome (RTS) is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma. A variety of benign and malignant hematologic abnormalities have been reported in affected individuals. The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, telangiectasias, and punctate atrophy (collectively known as poikiloderma) that persist throughout life. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities can include radial ray defects, ulnar defects, absent or hypoplastic patella, and osteopenia.
Rothmund-Thomson syndrome type 1
MedGen UID:
1684764
Concept ID:
C5231433
Disease or Syndrome
Rothmund-Thomson syndrome (RTS) is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma. A variety of benign and malignant hematologic abnormalities have been reported in affected individuals. The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, telangiectasias, and punctate atrophy (collectively known as poikiloderma) that persist throughout life. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities can include radial ray defects, ulnar defects, absent or hypoplastic patella, and osteopenia.
T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant
MedGen UID:
1712366
Concept ID:
C5394133
Disease or Syndrome
Infantile T-cell lymphopenia with or without nail dystrophy (TLIND) is an autosomal dominant disorder characterized by decreased numbers of T cells, particularly cytotoxic CD8+ T cells, usually apparent from infancy. Patients are often identified through newborn screening with the finding of low levels of T-cell receptor excision circles (TRECs). Affected individuals tend to be more susceptible to recurrent infections, mainly respiratory viral infections. However, the severity is highly variable, and patients usually improve with age later in childhood and as adults, even if CD8+ T cells remain decreased compared to normal. Additional features may include a small thymic shadow, indicative of impaired thymic development, skin abnormalities, such as atopic dermatitis, and nail dystrophy. As rare patients may develop more serious infections, affected individuals should be monitored. Bone marrow transplantation is not curative (summary by Bosticardo et al., 2019).
IFAP syndrome 1, with or without BRESHECK syndrome
MedGen UID:
1746744
Concept ID:
C5399971
Disease or Syndrome
The IFAP/BRESHECK syndrome is an X-linked multiple congenital anomaly disorder with variable severity. The classic triad, which defines IFAP, is ichthyosis follicularis, atrichia, and photophobia. Some patients have additional features, including mental retardation, brain anomalies, Hirschsprung disease, corneal opacifications, kidney dysplasia, cryptorchidism, cleft palate, and skeletal malformations, particularly of the vertebrae, which constitutes BRESHECK syndrome (summary by Naiki et al., 2012). Genetic Heterogeneity of IFAP Syndrome IFAP syndrome-2 (IFAP2; 619016) is caused by heterozygous mutation in the SREBF1 gene (184756) on chromosome 17p11.
IFAP syndrome 2
MedGen UID:
1763502
Concept ID:
C5436607
Disease or Syndrome
Follicular ichthyosis, atrichia, and photophobia syndrome-2 (IFAP2) is characterized by ichthyosis follicularis or follicular hyperkeratosis, sparse to no body hair, and photophobia with corneal lesions. Ultrastructural hair analysis shows trichorrhexis nodosa (Wang et al., 2020). For a discussion of genetic heterogeneity of IFAP syndrome, see IFAP1 (308205).
Mandibuloacral dysplasia progeroid syndrome
MedGen UID:
1741713
Concept ID:
C5436867
Disease or Syndrome
Mandibuloacral dysplasia progeroid syndrome (MDPS) is an autosomal recessive severe laminopathy-like disorder characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis, and hypertension (Elouej et al., 2020).
Olmsted syndrome 1
MedGen UID:
1778121
Concept ID:
C5542829
Disease or Syndrome
Olmsted syndrome-1 (OLMS1) is a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques with severe pruritus of lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas (summary by Lin et al., 2012). The digital constriction ('pseudoainhum') may progress to autoamputation of fingers and toes (Olmsted, 1927). Genetic Heterogeneity of Olmsted Syndrome Olmsted syndrome-2 (OLMS2; 619208) is caused by mutation in the PERP gene (609301) on chromosome 6q23. An X-linked form of Olmsted syndrome (OLMSX; 300918) is caused by mutation in the MBTPS2 gene (300294) on chromosome Xp22.
Epidermolysis bullosa simplex, Koebner type
MedGen UID:
1794134
Concept ID:
C5561924
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some instances) that results in non-scarring blisters and erosions caused by minor mechanical trauma. EBS is distinguished from other types of epidermolysis bullosa (EB) or non-EB skin fragility syndromes by the location of the blistering in relation to the dermal-epidermal junction. In EBS, blistering occurs within basal keratinocytes. The severity of blistering ranges from limited to hands and feet to widespread involvement. Additional features can include hyperkeratosis of the palms and soles (keratoderma), nail dystrophy, milia, and hyper- and/or hypopigmentation. Rare EBS subtypes have been associated with additional clinical features including pyloric atresia, muscular dystrophy, cardiomyopathy, and/or nephropathy.
Trichothiodystrophy 9, nonphotosensitive
MedGen UID:
1794268
Concept ID:
C5562058
Disease or Syndrome
Nonphotosensitive trichothiodystrophy-9 (TTD9) is characterized by brittle hair and nails and scaly skin, accompanied by failure to thrive, microcephaly, and neuromotor developmental delay. Hair analysis shows low sulfur content, and skin fibroblasts demonstrate normal DNA repair efficiency after UV irradiation (Botta et al., 2021). For a general phenotypic description and discussion of genetic heterogeneity of trichothiodystrophy, see TTD1 (601675).
Junctional epidermolysis bullosa with pyloric atresia
MedGen UID:
1810975
Concept ID:
C5676875
Disease or Syndrome
Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder). The course of EB-PA is usually severe and often lethal in the neonatal period. Most affected children succumb as neonates; those who survive may have severe blistering with formation of granulation tissue on the skin around the mouth, nose, fingers, and toes, and internally around the trachea. However, some affected individuals have little or no blistering later in life. Additional features shared by EB-PA and the other major forms of EB include congenital localized absence of skin (aplasia cutis congenita) affecting the extremities and/or head, milia, nail dystrophy, scarring alopecia, hypotrichosis, contractures, and dilated cardiomyopathy.
Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6
MedGen UID:
1805650
Concept ID:
C5676927
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Epidermolysis bullosa, junctional 5A, intermediate
MedGen UID:
1811851
Concept ID:
C5676956
Disease or Syndrome
Intermediate junctional epidermolysis bullosa 5A (JEB5A) is an autosomal recessive blistering disease of skin and mucous membranes. Blistering is less severe than in severe JEB (see 226700). The plane of skin cleavage is through the lamina lucida of the cutaneous basement membrane zone. Nails may be dystrophic and dental enamel defects are present. Blistering does not affect the life span of affected individuals (summary by Has et al., 2020). For a discussion of genetic heterogeneity of the subtypes of JEB, see JEB1A (226650). Reviews Has et al. (2020) reviewed the clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors, and natural history of epidermolysis bullosa.
Liver disease, severe congenital
MedGen UID:
1823968
Concept ID:
C5774195
Disease or Syndrome
Severe congenital liver disease (SCOLIV) is an autosomal recessive disorder characterized by the onset of progressive hepatic dysfunction usually in the first years of life. Affected individuals show feeding difficulties with failure to thrive and features such as jaundice, hepatomegaly, and abdominal distension. Laboratory workup is consistent with hepatic insufficiency and may also show coagulation defects, anemia, or metabolic disturbances. Cirrhosis and hypernodularity are commonly observed on liver biopsy. Many patients die of liver failure in early childhood (Moreno Traspas et al., 2022).
Dyskeratosis congenita, digenic
MedGen UID:
1823990
Concept ID:
C5774217
Disease or Syndrome
Digenic dyskeratosis congenita (DKCD) is characterized clinically by a combination of mucocutaneous features including abnormal skin pigmentation, nail dystrophy, thin hair, and oral leukoplakia. Some patients may have evidence of bone marrow failure, manifest as immune defects such as recurrent infections or hypogammaglobulinemia. Telomeres are shortened in patient cells. Individuals with DKCD may show severe adverse reactions to treatment with 5-FU (Tummala et al., 2022). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).
Dyskeratosis congenita, autosomal recessive 8
MedGen UID:
1824030
Concept ID:
C5774257
Disease or Syndrome
Autosomal recessive dyskeratosis congenita-8 (DKCB8) is characterized by progressive bone marrow failure affecting all lineages apparent from infancy or early childhood. More variable features may include poor growth, mild developmental delay, immunodeficiency, and gastrointestinal manifestations, such as esophageal stricture or inflammatory bowel disease. Some patients may have mucocutaneous features, including oral leukoplakia, nail dystrophy, or pigmentary skin abnormalities, although these features may be absent. Unlike patients with other forms of DKC, those with DKCB8 do not have shortened telomeres, although there is evidence of telomere instability. Hematopoietic stem cell transplant may be curative (Kermasson et al., 2022). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome
MedGen UID:
1824056
Concept ID:
C5774283
Disease or Syndrome
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH) is an autosomal dominant disorder characterized by choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. Additional features may include developmental delay, impaired intellectual development, and growth failure/retardation (summary by Cuvertino et al., 2020 and Baldridge et al., 2020).
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7
MedGen UID:
1841121
Concept ID:
C5830485
Disease or Syndrome
Telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-7 (PFBMFT7) is an autosomal dominant disorder characterized by variable manifestations associated with shortened telomeres. Features can include pulmonary fibrosis, emphysema, anemia, lymphopenia, liver involvement with portal hypertension and hepatopulmonary syndrome, premature graying of the hair, nail dystrophy, and predisposition to squamous cell cancers or myelodysplasia (Stanley et al., 2016). For a discussion of genetic heterogeneity of telomere-related pulmonary fibrosis and/or bone marrow failure syndromes, see PFBMFT1 (614742).
Neurodevelopmental disorder with language delay and variable cognitive abnormalities
MedGen UID:
1850358
Concept ID:
C5882689
Disease or Syndrome
Neurodevelopmental disorder with language delay and variable cognitive abnormalities (NEDLC) is a phenotypically heterogeneous neurologic disorder. Affected individuals may show early motor delay, speech and language delay, impaired intellectual development, learning disabilities, and/or behavioral abnormalities, although the severity and manifestations vary widely. Repetitive behavior and sleep difficulties are commonly present. More severe features include seizures, hypotonia, ocular abnormalities, dysmorphic features, and psychiatric comorbidities (Cediel et al., 2022).
Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities
MedGen UID:
1847702
Concept ID:
C5882696
Disease or Syndrome
Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities (ARCME) is characterized by severe dilated cardiomyopathy resulting in death or cardiac transplantation in childhood. Ventricular tachycardia, sustained or nonsustained, has been reported. In addition, some patients exhibit ectodermal manifestations including woolly or wiry hair, dental anomalies, dry skin, and/or dystrophic nails. Cleft lip and palate and corneal abnormalities have also been observed (Robinson et al., 2020; Henry et al., 2022).

Professional guidelines

PubMed

Iorizzo M, Tosti A, Starace M, Baran R, Daniel CR 3rd, Di Chiacchio N, Goettmann S, Grover C, Haneke E, Lipner SR, Rich P, Richert B, Rigopoulos D, Rubin AI, Zaiac M, Piraccini BM
J Am Acad Dermatol 2020 Dec;83(6):1717-1723. Epub 2020 Feb 26 doi: 10.1016/j.jaad.2020.02.056. PMID: 32112995
Halteh P, Scher RK, Lipner SR
Am J Clin Dermatol 2017 Dec;18(6):763-770. doi: 10.1007/s40257-017-0289-6. PMID: 28488241
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group
Arthritis Rheum 2006 Aug;54(8):2665-73. doi: 10.1002/art.21972. PMID: 16871531

Recent clinical studies

Etiology

Canal-García E, Bosch-Amate X, Belinchón I, Puig L
Actas Dermosifiliogr 2022 May;113(5):481-490. Epub 2022 Feb 2 doi: 10.1016/j.ad.2022.01.006. PMID: 35697407
Zrelski MM, Kustermann M, Winter L
Cells 2021 Sep 19;10(9) doi: 10.3390/cells10092480. PMID: 34572129Free PMC Article
AlSabbagh MM
J Dtsch Dermatol Ges 2020 Sep;18(9):943-967. Epub 2020 Sep 15 doi: 10.1111/ddg.14268. PMID: 32930426
Saper RB, Rash R
Am Fam Physician 2009 May 1;79(9):768-72. PMID: 20141096Free PMC Article
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group
Arthritis Rheum 2006 Aug;54(8):2665-73. doi: 10.1002/art.21972. PMID: 16871531

Diagnosis

Butt NI, Ashfaq F, Mahmood K, Aftab S, Anwar A, Saeed M
J Ayub Med Coll Abbottabad 2023 Jul-Sep;35(3):475-478. doi: 10.55519/JAMC-03-10849. PMID: 38404096
Canal-García E, Bosch-Amate X, Belinchón I, Puig L
Actas Dermosifiliogr 2022 May;113(5):481-490. Epub 2022 Feb 2 doi: 10.1016/j.ad.2022.01.006. PMID: 35697407
AlSabbagh MM
J Dtsch Dermatol Ges 2020 Sep;18(9):943-967. Epub 2020 Sep 15 doi: 10.1111/ddg.14268. PMID: 32930426
Iorizzo M, Tosti A, Starace M, Baran R, Daniel CR 3rd, Di Chiacchio N, Goettmann S, Grover C, Haneke E, Lipner SR, Rich P, Richert B, Rigopoulos D, Rubin AI, Zaiac M, Piraccini BM
J Am Acad Dermatol 2020 Dec;83(6):1717-1723. Epub 2020 Feb 26 doi: 10.1016/j.jaad.2020.02.056. PMID: 32112995
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group
Arthritis Rheum 2006 Aug;54(8):2665-73. doi: 10.1002/art.21972. PMID: 16871531

Therapy

Egger A, Tosti A
J Am Acad Dermatol 2020 Dec;83(6):1724-1729. Epub 2020 Mar 19 doi: 10.1016/j.jaad.2020.03.023. PMID: 32199899
Iorizzo M, Tosti A, Starace M, Baran R, Daniel CR 3rd, Di Chiacchio N, Goettmann S, Grover C, Haneke E, Lipner SR, Rich P, Richert B, Rigopoulos D, Rubin AI, Zaiac M, Piraccini BM
J Am Acad Dermatol 2020 Dec;83(6):1717-1723. Epub 2020 Feb 26 doi: 10.1016/j.jaad.2020.02.056. PMID: 32112995
Halteh P, Scher RK, Lipner SR
Am J Clin Dermatol 2017 Dec;18(6):763-770. doi: 10.1007/s40257-017-0289-6. PMID: 28488241
Saper RB, Rash R
Am Fam Physician 2009 May 1;79(9):768-72. PMID: 20141096Free PMC Article
Iorizzo M, Piraccini BM, Tosti A
J Cosmet Dermatol 2007 Mar;6(1):53-8. doi: 10.1111/j.1473-2165.2007.00290.x. PMID: 17348997

Prognosis

Samson P, Curvale C, Iniesta A, Gay A
Hand Surg Rehabil 2024 Apr;43S:101526. doi: 10.1016/j.hansur.2022.12.007. PMID: 38879227
Lencastre A, Arnal C, Richert B
Hand Surg Rehabil 2024 Apr;43S:101651. Epub 2024 Jan 29 doi: 10.1016/j.hansur.2024.101651. PMID: 38296187
Sehgal VN, Chatterjee K, Malhotra S
Skinmed 2018;16(2):119. Epub 2018 Apr 1 PMID: 29911530
Wilson FC, Icen M, Crowson CS, McEvoy MT, Gabriel SE, Kremers HM
Arthritis Rheum 2009 Feb 15;61(2):233-9. doi: 10.1002/art.24172. PMID: 19177544Free PMC Article
Haneke E, Baran R
Dermatol Surg 2001 Jun;27(6):580-4. PMID: 11442597

Clinical prediction guides

Chi MH, Chung WH, Hui RC, Chen CB, Lu CW, Chiu TM, Ma DH, Wang CW, Yang CY; Taiwan Severe Cutaneous Adverse Reaction Consortium
J Dermatol 2022 Sep;49(9):895-902. Epub 2022 Jun 17 doi: 10.1111/1346-8138.16476. PMID: 35715971
Çevik HB, Çiçek ÇA, Kayahan S, Gümüstas SA, Filinte GT
Handchir Mikrochir Plast Chir 2021 Feb;53(1):72-75. Epub 2021 Feb 15 doi: 10.1055/a-1333-2459. PMID: 33588493
Tosti A, de Farias DC, Murrell DF
Dermatol Clin 2010 Jan;28(1):153-7. doi: 10.1016/j.det.2009.10.017. PMID: 19945629
Wilson FC, Icen M, Crowson CS, McEvoy MT, Gabriel SE, Kremers HM
Arthritis Rheum 2009 Feb 15;61(2):233-9. doi: 10.1002/art.24172. PMID: 19177544Free PMC Article
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group
Arthritis Rheum 2006 Aug;54(8):2665-73. doi: 10.1002/art.21972. PMID: 16871531

Recent systematic reviews

Kiely AL, Nolan GS, Cooper LRL
J Hand Surg Am 2022 Dec;47(12):1223.e1-1223.e20. Epub 2021 Nov 19 doi: 10.1016/j.jhsa.2021.08.022. PMID: 34810026
Tang JY, Marinkovich MP, Lucas E, Gorell E, Chiou A, Lu Y, Gillon J, Patel D, Rudin D
Orphanet J Rare Dis 2021 Apr 13;16(1):175. doi: 10.1186/s13023-021-01811-7. PMID: 33849616Free PMC Article
Kim WB, Alavi A, Walsh S, Kim S, Pope E
Am J Clin Dermatol 2015 Apr;16(2):81-7. doi: 10.1007/s40257-015-0119-7. PMID: 25690953
Klaassen KM, Dulak MG, van de Kerkhof PC, Pasch MC
J Eur Acad Dermatol Venereol 2014 May;28(5):533-41. Epub 2013 Aug 19 doi: 10.1111/jdv.12239. PMID: 24033871

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