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Alopecia

MedGen UID:
7982
Concept ID:
C0002170
Disease or Syndrome; Finding
Synonyms: Baldness; Hair Loss; Hair Losses; Loss, Hair; Losses, Hair
SNOMED CT: Loss of hair (278040002); Falling hair (278040002); Thinning hair (278040002); Bald (56317004); Hair loss disorder (56317004); Alopecia (56317004); Baldness (56317004)
 
Related gene: HR
 
HPO: HP:0001596
Monarch Initiative: MONDO:0004907
Orphanet: ORPHA79364

Definition

A noncongenital process of hair loss, which may progress to partial or complete baldness. [from HPO]

Term Hierarchy

Conditions with this feature

Progressive myositis ossificans
MedGen UID:
4698
Concept ID:
C0016037
Disease or Syndrome
Fibrodysplasia ossificans progressiva (FOP) is characterized by congenital bilateral hallux valgus malformations and early-onset heterotopic ossification, which may be spontaneous or precipitated by trauma including intramuscular vaccinations. Painful, recurrent soft-tissue swellings (flare-ups) may precede localized heterotopic ossification. Heterotopic ossification can occur at any location, but typically affects regions in close proximity to the axial skeleton in the early/mild stages, before progressing to the appendicular skeleton. This can lead to restriction of movement as a result of ossification impacting joint mobility. Problems with swallowing and speaking can occur with ossification affecting the jaw, head, and neck, and restriction of the airway and breathing may lead to thoracic insufficiency syndrome.
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.
Ito hypomelanosis
MedGen UID:
5920
Concept ID:
C0022283
Congenital Abnormality
A large brown, blue, or gray hamartoma of dermal melanocytes, usually on the shoulder and upper arm that is most commonly found in Asian populations and in females. It is sometimes associated with sensory changes in the involved skin area, but very rarely becomes cancerous.
Menkes kinky-hair syndrome
MedGen UID:
44030
Concept ID:
C0022716
Disease or Syndrome
Menkes disease (MNK) is an X-linked recessive disorder characterized by generalized copper deficiency. The clinical features result from the dysfunction of several copper-dependent enzymes.
Hutchinson-Gilford syndrome
MedGen UID:
46123
Concept ID:
C0033300
Disease or Syndrome
Hutchinson-Gilford progeria syndrome (HGPS) is characterized by clinical features that typically develop in childhood and resemble some features of accelerated aging. Children with HGPS usually appear normal at birth. Profound failure to thrive occurs during the first year. Characteristic facial features include head that is disproportionately large for the face, narrow nasal ridge, narrow nasal tip, thin vermilion of the upper and lower lips, small mouth, and retro- and micrognathia. Common features include loss of subcutaneous fat, delayed eruption and loss of primary teeth, abnormal skin with small outpouchings over the abdomen and upper thighs, alopecia, nail dystrophy, coxa valga, and progressive joint contractures. Later findings include low-frequency conductive hearing loss, dental crowding, and partial lack of secondary tooth eruption. Motor and mental development is normal. Death occurs as a result of complications of severe atherosclerosis, either cardiac disease (myocardial infarction or heart failure) or cerebrovascular disease (stroke), generally between ages six and 20 years. Average life span is approximately 14.5 years.
Trichotillomania
MedGen UID:
21654
Concept ID:
C0040953
Mental or Behavioral Dysfunction
Trichotillomania (TTM) is a neuropsychiatric disorder characterized by chronic, repetitive, or compulsive hair pulling resulting in noticeable hair loss. The activity causes distress to the individual and often interferes with functioning. Affected individuals may develop physical complications and often have overlapping psychologic disorders, such as Tourette syndrome (GTS; 137580) or obsessive-compulsive disorder (OCD; 164230) (review by Novak et al., 2009).
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.
Polyglandular autoimmune syndrome, type 1
MedGen UID:
39125
Concept ID:
C0085859
Disease or Syndrome
Autoimmune polyglandular syndrome type I 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 longterm follow-up, the development of additional features of APS1 may be observed (Cranston et al., 2022).
Polyglandular autoimmune syndrome, type 2
MedGen UID:
39126
Concept ID:
C0085860
Disease or Syndrome
Autoimmune polyendocrine syndrome type II (APS2), or Schmidt syndrome, is characterized by the presence of autoimmune Addison disease in association with either autoimmune thyroid disease or type I diabetes mellitus, or both. Chronic candidiasis is not present. APS2 may occur at any age and in both sexes, but is most common in middle-aged females and is very rare in childhood (summary by Betterle et al., 2004). See 240300 for a phenotypic description of autoimmune polyendocrine syndrome type I (APS1).
Adrenoleukodystrophy
MedGen UID:
57667
Concept ID:
C0162309
Disease or Syndrome
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and the adrenal cortex. Three main phenotypes are seen in affected males: The childhood cerebral form manifests most commonly between ages four and eight years. It initially resembles attention-deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years. Most individuals have impaired adrenocortical function at the time that neurologic disturbances are first noted. Adrenomyeloneuropathy (AMN) manifests most commonly in an individual in his twenties or middle age as progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical function; all symptoms are progressive over decades. "Addison disease only" presents with primary adrenocortical insufficiency between age two years and adulthood and most commonly by age 7.5 years, without evidence of neurologic abnormality; however, some degree of neurologic disability (most commonly AMN) usually develops by middle age. More than 20% of female carriers develop mild-to-moderate spastic paraparesis in middle age or later. Adrenal function is usually normal.
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.
Cutaneous porphyria
MedGen UID:
102408
Concept ID:
C0162530
Disease or Syndrome
Congenital erythropoietic porphyria (CEP) is characterized in most individuals by severe cutaneous photosensitivity with blistering and increased friability of the skin over light-exposed areas. Onset in most affected individuals occurs at birth or early infancy. The first manifestation is often pink-to-dark red discoloration of the urine. Hemolytic anemia is common and can range from mild to severe, with some affected individuals requiring chronic blood transfusions. Porphyrin deposition may lead to corneal ulcers and scarring, reddish-brown discoloration of the teeth (erythrodontia), and bone loss and/or expansion of the bone marrow. The phenotypic spectrum, however, is broad and ranges from nonimmune hydrops fetalis in utero to late-onset disease with only mild cutaneous manifestations in adulthood.
Biotinidase deficiency
MedGen UID:
66323
Concept ID:
C0220754
Disease or Syndrome
If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.
Perifolliculitis capitis abscedens et suffodiens
MedGen UID:
78097
Concept ID:
C0263506
Disease or Syndrome
Perifolliculitis capitis abscedens et suffodiens is a chronic inflammatory disease of the scalp characterized by the presence of large and small nodules that suppurate and intercommunicate by sinus formation. It may be more frequent in black males than in others (summary by McMullan and Zeligman, 1956).
Child syndrome
MedGen UID:
82697
Concept ID:
C0265267
Disease or Syndrome
The NSDHL-related disorders include: CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked condition that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked disorder that affects males. CHILD syndrome is characterized by unilateral distribution of ichthyosiform (yellow scaly) skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life; new lesions can develop in later life. Nail changes are also common. The heart, lung, and kidneys can also be involved. CK syndrome (named for the initials of the original proband) is characterized by mild to severe cognitive impairment and behavior problems (aggression, attention deficit hyperactivity disorder, and irritability). All affected males reported have developed seizures in infancy and have cerebral cortical malformations and microcephaly. All have distinctive facial features, a thin habitus, and relatively long, thin fingers and toes. Some have scoliosis and kyphosis. Strabismus is common. Optic atrophy is also reported.
Pallister-Killian syndrome
MedGen UID:
120540
Concept ID:
C0265449
Disease or Syndrome
Pallister-Killian syndrome (PKS) is a dysmorphic condition involving most organ systems, but is also characterized by a tissue-limited mosaicism; most fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. The extra metacentric chromosome is an isochromosome for part of the short arm of chromosome 12: i(12)(p10) (Peltomaki et al., 1987; Warburton et al., 1987).
Alopecia, congenital
MedGen UID:
78581
Concept ID:
C0265992
Congenital Abnormality
A congenital condition characterized by the absence of hair on the scalp or entire body. The lack of hair is rarely absolute and is usually accompanied by incompletely grown, lanugo-like hair. It affects males twice as much as females and a familial tendency is common.
Pili torti-deafness syndrome
MedGen UID:
82728
Concept ID:
C0266006
Disease or Syndrome
Bjornstad syndrome (BJS) is an autosomal recessive disorder characterized by sensorineural hearing loss and pili torti. The hearing loss is congenital and of variable severity. Pili torti (twisted hairs), a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair very brittle, is usually recognized early in childhood (Selvaag, 2000).
Triglyceride storage disease with ichthyosis
MedGen UID:
82780
Concept ID:
C0268238
Disease or Syndrome
Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive nonlysosomal inborn error of neutral lipid metabolism. Patients present with an nonbullous erythrodermic form of ichthyosis, with variable involvement of other organs, such as liver, central nervous system, eyes, and ears. Intracellular triacylglycerol droplets are present in most tissues, and diagnosis can be confirmed by a simple blood smear, in which the characteristic lipid droplets are observed in the cytoplasm of granulocytes (summary by Lefevre et al., 2001).
Familial porphyria cutanea tarda
MedGen UID:
75669
Concept ID:
C0268323
Disease or Syndrome
Familial porphyria cutanea tarda (F-PCT) is characterized by: skin findings including blistering over the dorsal aspects of the hands and other sun-exposed areas of skin, skin friability after minor trauma, facial hypertrichosis and hyperpigmentation, and severe thickening of affected skin areas (pseudoscleroderma); and an increased risk for hepatocellular carcinoma (HCC).
Alstrom syndrome
MedGen UID:
78675
Concept ID:
C0268425
Disease or Syndrome
Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive bilateral sensorineural hearing impairment, acute infantile-onset cardiomyopathy and/or adolescent- or adult-onset restrictive cardiomyopathy, insulin resistance / type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), and chronic progressive kidney disease. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Sensorineural hearing loss presents in the first decade in as many as 70% of individuals and may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to T2DM in the majority by the third decade. Nearly all demonstrate hypertriglyceridemia. Other findings can include endocrine abnormalities (hypothyroidism, hypogonadotropic hypogonadism in males, and hyperandrogenism in females), urologic dysfunction / detrusor instability, progressive decrease in renal function, and hepatic disease (ranging from elevated transaminases to steatohepatitis/NAFLD). Approximately 20% of affected individuals have delay in early developmental milestones, most commonly in gross and fine motor skills. About 30% have a learning disability. Cognitive impairment (IQ <70) is very rare. Wide clinical variability is observed among affected individuals, even within the same family.
Holocarboxylase synthetase deficiency
MedGen UID:
120653
Concept ID:
C0268581
Disease or Syndrome
Holocarboxylase synthetase deficiency, a biotin-responsive multiple carboxylase deficiency (MCD), is characterized by metabolic acidosis, lethargy, hypotonia, convulsions, and dermatitis. Most patients present in the newborn or early infantile period, but some become symptomatic in the later infantile period (summary by Suzuki et al., 2005). Also see biotinidase deficiency (253260), another form of MCD with a later onset. Care must be taken to differentiate the inherited multiple carboxylase deficiencies from acquired biotin deficiencies, such as those that develop after excessive dietary intake of avidin, an egg-white glycoprotein that binds specifically and essentially irreversibly to biotin (Sweetman et al., 1981) or prolonged parenteral alimentation without supplemental biotin (Mock et al., 1981).
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).
Woodhouse-Sakati syndrome
MedGen UID:
83337
Concept ID:
C0342286
Disease or Syndrome
Virtually all individuals with Woodhouse-Sakati syndrome (WSS) have the endocrine findings of hypogonadism (evident at puberty) and progressive childhood-onset hair thinning that often progresses to alopecia totalis in adulthood. More than half of individuals have the neurologic findings of progressive extrapyramidal movements (dystonic spasms with dystonic posturing with dysarthria and dysphagia), moderate bilateral postlingual sensorineural hearing loss, and mild intellectual disability. To date, more than 40 families (including 33 with a molecularly confirmed diagnosis) with a total of 88 affected individuals have been reported in the literature.
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
MedGen UID:
83339
Concept ID:
C0342288
Disease or Syndrome
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, endocrinopathy (most commonly insulin-dependent diabetes mellitus), and eczematous dermatitis. Most children have other autoimmune phenomena including cytopenias, autoimmune hepatitis, or nephropathy; lymphadenopathy, splenomegaly, alopecia, arthritis, and lung disease related to immune dysregulation have all been observed. Fetal presentation of IPEX includes hydrops, echogenic bowel, skin desquamation, IUGR, and fetal akinesia. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected males die within the first one to two years of life from metabolic derangements, severe malabsorption, or sepsis; a few with a milder phenotype have survived into the second or third decade of life.
Flynn-Aird syndrome
MedGen UID:
91009
Concept ID:
C0343108
Disease or Syndrome
A rare genetic disease characterized by childhood onset of bilateral progressive sensorineural hearing loss, ocular anomalies (myopia, cataract, retinitis pigmentosa), central and peripheral nervous system features (dementia, epilepsy, ataxia, peripheral neuropathy), ectodermal features (skin atrophy, alopecia, dental caries), and skeletal anomalies (bone cysts, joint stiffness, scoliosis, kyphosis). Laboratory examination may reveal elevated cerebrospinal fluid protein.
Neonatal pseudo-hydrocephalic progeroid syndrome
MedGen UID:
140806
Concept ID:
C0406586
Disease or Syndrome
Wiedemann-Rautenstrauch syndrome (WDRTS) is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, hypotonia, and variable mental impairment (summary by Toriello, 1990). Average survival in WDRTS is 7 months, although survival into the third decade of life has been reported (Akawi et al., 2013).
Encephalocraniocutaneous lipomatosis
MedGen UID:
140807
Concept ID:
C0406612
Congenital Abnormality
Encephalocraniocutaneous lipomatosis (ECCL) comprises a spectrum of predominantly congenital anomalies. In its typical form, ECCL is characterized by congenital anomalies of the skin (nevus psiloliparus, patchy or streaky non-scarring alopecia, subcutaneous lipomas in the frontotemporal region, focal skin aplasia or hypoplasia on the scalp, and/or small nodular skin tags on the eyelids or between the outer canthus and tragus), eye (choristoma), and brain (in particular intracranial and spinal lipomas). To a much lesser degree, the bones and the heart can be affected. About 40% of affected individuals have bilateral abnormalities of the skin or the eyes. About one third of affected individuals have normal cognitive development, another one third have mild developmental delay (DD) or intellectual disability (ID), and the final one third have severe or unspecified DD/ID. Half of individuals have seizures. Affected individuals are at an increased (i.e., above the general population) risk of developing brain tumors, particularly low-grade gliomas such as pilocytic astrocytomas. There is evidence that oculoectodermal syndrome (OES) may constitute a clinical spectrum with ECCL, with OES on the mild end and ECCL on the more severe end of the spectrum.
GAPO syndrome
MedGen UID:
98034
Concept ID:
C0406723
Disease or Syndrome
GAPO syndrome is the acronymic designation for a complex of growth retardation, alopecia, pseudoanodontia (failure of tooth eruption), and progressive optic atrophy (Tipton and Gorlin, 1984). Ilker et al. (1999) and Bayram et al. (2014) noted that optic atrophy is not a consistent feature of the disorder.
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).
Alopecia - contractures - dwarfism - intellectual disability syndrome
MedGen UID:
167081
Concept ID:
C0795895
Disease or Syndrome
A form of ectodermal dysplasia syndrome characterized by a short stature of prenatal onset, alopecia, ichthyosis, photophobia, ectrodactyly, seizures, scoliosis, multiple contractures, fusions of various bones (particularly elbows, carpals, metacarpals, and spine), intellectual disability, and facial dysmorphism (microdolichocephaly, madarosis, large ears and long nose). ACD syndrome overlaps with ichthyosis follicularis-alopecia-photophobia syndrome.
Gomez Lopez Hernandez syndrome
MedGen UID:
163201
Concept ID:
C0795959
Disease or Syndrome
Gomez-Lopez-Hernandez syndrome (GLHS), also known as cerebellotrigeminal dermal dysplasia, is a rare neurocutaneous syndrome classically characterized by the triad of rhombencephalosynapsis, trigeminal anesthesia, often giving rise to corneal opacities, and bilateral parietal or parietooccipital alopecia. However, trigeminal anesthesia is an inconsistent finding (summary by Sukhudyan et al., 2010).
Oculocerebrocutaneous syndrome
MedGen UID:
163214
Concept ID:
C0796092
Disease or Syndrome
A rare neurologic disease typically characterized by the triad of eye, central nervous system and skin malformations, and often associated with an intellectual disability.
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).
Autosomal recessive keratitis-ichthyosis-deafness syndrome
MedGen UID:
224809
Concept ID:
C1275089
Disease or Syndrome
Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR) is characterized by neonatal-onset ichthyotic erythroderma and profound sensorineural deafness, with failure to thrive and developmental delay in childhood. Severe corneal scarring with vision loss has been observed in adulthood. Low plasma copper and ceruloplasmin levels have been reported in some patients (Alsaif et al., 2019; Boyden et al., 2019). An autosomal dominant form of KID syndrome (KIDAD; 148210) is caused by mutation in the GJB2 gene (121011) on chromosome 13q12. Mutation in the AP1S1 gene (603531) causes a disorder with overlapping features (MEDNIK; 609313).
Orofaciodigital syndrome I
MedGen UID:
307142
Concept ID:
C1510460
Disease or Syndrome
Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following features: Oral (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities). Facial (widely spaced eyes or telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft upper lip, micrognathia). Digital (brachydactyly, syndactyly, clinodactyly of the fifth finger; duplicated hallux [great toe]). Kidney (polycystic kidney disease). Brain (e.g., intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation). Intellectual disability (in ~50% of individuals).
Satoyoshi syndrome
MedGen UID:
318882
Concept ID:
C1833454
Disease or Syndrome
Satoyoshi syndrome is a rare disorder characterized by progressive, painful, intermittent muscle spasms, diarrhea or unusual malabsorption, endocrinopathy with amenorrhea, and secondary skeletal abnormalities. The disorder is also called komuragaeri disease by the Japanese; in Japanese 'komura' means calf and 'gaeri' means 'turnover' or spasm. All cases have apparently been sporadic, even when occurring in large families (Ehlayel and Lacassie, 1995).
DK1-congenital disorder of glycosylation
MedGen UID:
332072
Concept ID:
C1835849
Disease or Syndrome
DOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im) is an inherited condition that often affects the heart but can also involve other body systems. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.\n\nIndividuals with DOLK-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Nearly all individuals with DOLK-CDG develop a weakened and enlarged heart (dilated cardiomyopathy). Other frequent signs and symptoms include recurrent seizures; developmental delay; poor muscle tone (hypotonia); and dry, scaly skin (ichthyosis). Less commonly, affected individuals can have distinctive facial features, kidney disease, hormonal abnormalities, or eye problems.\n\nIndividuals with DOLK-CDG typically do not survive into adulthood, often because of complications related to dilated cardiomyopathy, and some do not survive past infancy.
Mandibuloacral dysplasia with type B lipodystrophy
MedGen UID:
332940
Concept ID:
C1837756
Disease or Syndrome
Mandibuloacral dysplasia with type B lipodystrophy (MADB) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies such as mandibular hypoplasia, skeletal anomalies such as progressive osteolysis of the terminal phalanges and clavicles, and skin changes such as mottled hyperpigmentation and atrophy. The lipodystrophy is characterized by generalized loss of subcutaneous fat involving the face, trunk, and extremities. Some patients have a progeroid appearance. Metabolic complications associated with insulin resistance have been reported (Schrander-Stumpel et al., 1992; summary by Simha et al., 2003). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370).
PARC syndrome
MedGen UID:
373923
Concept ID:
C1838256
Disease or Syndrome
A rare genetic developmental defect during embryogenesis. A syndrome characterized by the association of congenital poikiloderma (P), generalized alopecia (A), retrognathism (R) and cleft palate (C). There have been no further descriptions in the literature since 1990.
CARASIL syndrome
MedGen UID:
325051
Concept ID:
C1838577
Disease or Syndrome
HTRA1 disorder is a phenotypic spectrum in which some individuals have few to no symptoms and others manifest with the more severe CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) phenotype. Those who have a heterozygous HTRA1 pathogenic variant may have mild neurologic findings (sometimes identified only on neuroimaging) or mild-to-moderate neurologic signs and symptoms of CARASIL. In this chapter, the term "classic CARASIL" refers to the more severe phenotype associated with biallelic pathogenic variants, and "HTRA1 cerebral small vessel disease" (HTRA1-CSVD) refers to the milder phenotype associated with a heterozygous HTRA1 pathogenic variant. Classic CARASIL is characterized by early-onset changes in the deep white matter of the brain observed on MRI, and associated neurologic findings. The most frequent initial symptom is gait disturbance from spasticity beginning between ages 20 and 40 years. Forty-four percent of affected individuals have stroke-like episodes before age 40 years. Mood changes (apathy and irritability), pseudobulbar palsy, and cognitive dysfunction begin between ages 20 and 50 years. The disease progresses slowly following the onset of neurologic symptoms. Scalp alopecia and acute mid- to lower-back pain (lumbago) before age 30 years are characteristic. The most frequent initial symptom in individuals with HTRA1-CSVD is slowly progressive gait disturbance after age 40 years, which may be followed by the development of mood changes and cognitive dysfunction. A majority of affected individuals have a stroke-like episode after age 40 years. Spondylosis and alopecia are seen in a minority of individuals with HTRA1-CSVD.
Zinc deficiency, transient neonatal
MedGen UID:
330858
Concept ID:
C1842486
Disease or Syndrome
Transient neonatal zinc deficiency occurs in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is required for normal growth particularly in infants, and breast milk normally contains adequate zinc to meet the requirement for infants up to 4 to 6 months of age. Zinc deficiency can lead to dermatitis, alopecia, decreased growth, and impaired immune function. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Chowanadisai et al., 2006). Some aspects of TNZD resemble the more severe disorder acrodermatitis enteropathica (AEZ; 201100), an autosomal recessive disorder caused by mutation in the zinc transporter SLC39A4 (607059). However, infants with transient neonatal zinc deficiency do not require zinc supplementation following weaning and have normal zinc absorption, whereas those with AEZ require lifelong zinc supplementation (summary by Chowanadisai et al., 2006).
Hypotrichosis-lymphedema-telangiectasia syndrome
MedGen UID:
375070
Concept ID:
C1843004
Disease or Syndrome
Hypotrichosis-lymphedema-telangiectasia syndrome is an autosomal recessive disorder characterized by these 3 features, which begin at birth or in early childhood and are progressive (summary by Irrthum et al., 2003).
Neonatal ichthyosis-sclerosing cholangitis syndrome
MedGen UID:
334382
Concept ID:
C1843355
Disease or Syndrome
A very rare complex ichthyosis syndrome with characteristics of scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. The ichthyosis presents with diffuse white scales sparing the skin folds and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly and biochemical cholestasis. Caused by a mutation in the CLDN1 gene on chromosome 3q28 coding for the tight junction protein claudin-1. Autosomal recessive pattern of inheritance.
Trichomegaly-retina pigmentary degeneration-dwarfism syndrome
MedGen UID:
338532
Concept ID:
C1848745
Disease or Syndrome
PNPLA6 disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia; upper motor neuron involvement manifesting as spasticity and/or brisk reflexes; chorioretinal dystrophy associated with variable degrees of reduced visual function; and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). The hypogonadotropic hypogonadism occurs either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting); hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia); short stature; and impaired cognitive functioning (learning disabilities in children; deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia).
Bartsocas-Papas syndrome 1
MedGen UID:
337894
Concept ID:
C1849718
Disease or Syndrome
Bartsocas-Papas syndrome-1 (BPS1) is an autosomal recessive disorder characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly. Early lethality is common, although survival into childhood and beyond has been reported (summary by Mitchell et al., 2012). Genetic Heterogeneity of Bartsocas-Papas Syndrome Bartsocas-Papas syndrome-2 (BPS2) is caused by mutation in the CHUK gene (600664). A less severe form of popliteal pterygium syndrome (PPS; 119500) is caused by mutation in the IRF6 gene (607199).
Pili torti-developmental delay-neurological abnormalities syndrome
MedGen UID:
342358
Concept ID:
C1849811
Disease or Syndrome
Abnormal hair, joint laxity, and developmental delay (HJDD) is characterized by normal hair at birth that gradually becomes sparse, twisted, brittle, and easily broken, with pili torti and trichorrhexis nodosa observed on light microscopy. Other features include increased joint mobility and cognitive delay (Sharma et al., 2019).
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.
Ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome
MedGen UID:
344577
Concept ID:
C1855788
Disease or Syndrome
An ectodermal dysplasia syndrome characterized by severe generalized lamellar icthyosis at birth with alopecia, eclabium, ectropion and intellectual disability. Although similar to Sjogren-Larsson syndrome, this syndrome lacks the presence of neurologic or macular changes. There have been no further descriptions in the literature since 1987.
Rhizomelic chondrodysplasia punctata type 1
MedGen UID:
347072
Concept ID:
C1859133
Disease or Syndrome
Rhizomelic chondrodysplasia punctata type 1 (RCDP1), a peroxisome biogenesis disorder (PBD) has a classic (severe) form and a nonclassic (mild) form. Classic (severe) RCDP1 is characterized by proximal shortening of the humerus (rhizomelia) and to a lesser degree the femur, punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities (chondrodysplasia punctata, or CDP), coronal clefts of the vertebral bodies, and cataracts that are usually present at birth or appear in the first few months of life. Birth weight, length, and head circumference are often at the lower range of normal; postnatal growth deficiency is profound. Intellectual disability is severe, and the majority of children develop seizures. Most affected children do not survive the first decade of life; a proportion die in the neonatal period. Nonclassic (mild) RCDP1 is characterized by congenital or childhood cataracts, CDP or infrequently, chondrodysplasia manifesting only as mild epiphyseal changes, variable rhizomelia, and milder intellectual disability and growth restriction than classic RCDP1.
Celiac disease, susceptibility to, 1
MedGen UID:
395227
Concept ID:
C1859310
Finding
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
3-methylcrotonyl-CoA carboxylase 2 deficiency
MedGen UID:
347898
Concept ID:
C1859499
Disease or Syndrome
3-Methylcrotonylglycinuria is an autosomal recessive disorder of leucine catabolism. The clinical phenotype is highly variable, ranging from neonatal onset with severe neurologic involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency. MCC activity in extracts of cultured fibroblasts of patients is usually less than 2% of control (summary by Baumgartner et al., 2001). Also see 3-methylcrotonylglycinuria I (MCC1D; 210200), caused by mutation in the alpha subunit of 3-methylcrotonyl-CoA carboxylase (MCCC1; 609010).
Alopecia-intellectual disability syndrome 1
MedGen UID:
349263
Concept ID:
C1859878
Disease or Syndrome
Alopecia-intellectual disability syndrome (APMR) is a rare autosomal recessive disorder in which affected individuals show loss of hair on the scalp, absence of eyebrows, eyelashes, and axillary and pubic hair, and mildly to severely impaired intellectual development (summary by Wali et al., 2007). Genetic Heterogeneity of Alopecia-Intellectual Disability Syndrome Loci for alopecia-intellectual disability syndrome have been mapped to chromosome 3q26.2-q26.31 (APMR2; 610422) and chromosome 18q11.2-q12.2 (APMR3; 613930). APMR4 (618840) is caused by mutation in the LSS gene (600909) on chromosome 21q22.
Thumb deformity-alopecia-pigmentation anomaly syndrome
MedGen UID:
348284
Concept ID:
C1861168
Disease or Syndrome
Thumb deformity-alopecia-pigmentation anomaly syndrome is a rare, genetic, congenital limb malformation syndrome characterized by short stature, sparse scalp hair, hypoplastic, proximally-placed thumbs, and skin hyperpigmentation with areas of 'raindrop' depigmentation. Presence of a single, upper central incisor has also been reported. There have been no further descriptions in the literature since 1988.
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.
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).
Primary hypergonadotropic hypogonadism-partial alopecia syndrome
MedGen UID:
388650
Concept ID:
C2673480
Disease or Syndrome
This syndrome is characterized by primary hypergonadotropic hypogonadism and partial alopecia.
ANE syndrome
MedGen UID:
394313
Concept ID:
C2677535
Disease or Syndrome
Alopecia, neurologic defects, and endocrinopathy syndrome (ANES) is an autosomal recessive disorder characterized by alopecia with skin involvement including multiple facial nevi and flexural hyperpigmentation; moderately to severely impaired intellectual development; progressive motor decline; and endocrine deficiency (summary by Spiegel et al., 2010).
Histiocytic medullary reticulosis
MedGen UID:
398130
Concept ID:
C2700553
Disease or Syndrome
Omenn syndrome is an autosomal recessive disorder characterized by severe combined immunodeficiency (SCID) associated with erythrodermia, hepatosplenomegaly, lymphadenopathy, and alopecia. B cells are mostly absent, T-cell counts are normal to elevated, and T cells are frequently activated and express a restricted T-cell receptor (TCR) repertoire (summary by Ege et al., 2005). Another distinct form of familial histiocytic reticulocytosis (267700) is caused by mutation in the perforin-1 gene (PRF1; 170280) on chromosome 10q22.
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).
Hypotrichosis 5
MedGen UID:
440568
Concept ID:
C2748535
Disease or Syndrome
Hypotrichosis-5 (HYPT5), also known as Marie Unna hereditary hypotrichosis-2 (MUHH2), is a form of hereditary hypotrichosis characterized by twisting hair. Affected individuals have little or no scalp hair at birth, wiry and irregular scalp hair in childhood, and sparse or no forehead and parietal hair at puberty. Eyebrows and eyelashes are thin, and pubic and axillary hair fails to develop. Scarring alopecia is modest, and vertex hair is normal (summary by Zhang et al., 2012). For a general phenotypic description of Marie Unna hereditary hypotrichosis, see MUHH1 (146550). For a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see 605389.
Vitamin D-dependent rickets, type 2B
MedGen UID:
411667
Concept ID:
C2748783
Disease or Syndrome
Vitamin D-dependent rickets type 2B with normal vitamin D receptor (VDDR2B) is an unusual form of rickets due to abnormal expression of a hormone response element-binding protein that interferes with the normal function of the vitamin D receptor. Vitamin D-dependent rickets type 2A (VDDR2A) is caused by mutation in the vitamin D receptor gene (VDR; 601769), and most patients have alopecia in addition to rickets. For a general phenotypic description and a discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700).
Hypotrichosis 4
MedGen UID:
413053
Concept ID:
C2750815
Disease or Syndrome
Hypotrichosis-4 (HYPT4), also known as Marie Unna hereditary hypotrichosis-1 (MUHH1), is an autosomal dominant form of hair loss characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth. Coarse, wiry hair begins to grow during childhood. Around puberty, progressive hair loss occurs in the affected patients. Although the disorder has the potential to affect all hair shafts, progressive and patterned alopecia of the scalp is the main manifestation of the disorder (summary by Mansur et al., 2010). For a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see 605389. Genetic Heterogeneity of Marie Unna Hereditary Hypotrichosis See also MUHH2 (HYPT5; 612841), caused by heterozygous mutation in the EPS8L3 gene (614989) on chromosome 1p13.
RIN2 syndrome
MedGen UID:
416526
Concept ID:
C2751321
Disease or Syndrome
A very rare inherited connective tissue disorder with characteristics of macrocephaly, sparse scalp hair, soft redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rare manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly have also been reported. Caused by homozygous mutation in the RIN2 gene on chromosome 20p11.
Candidiasis, familial, 1
MedGen UID:
414015
Concept ID:
C2751429
Disease or Syndrome
Chronic mucocutaneous candidiasis (CMC) includes a group of rare disorders with altered immune responses, selective against Candida, characterized by persistent and/or recurrent infections of the skin, nails, and mucous membranes, caused by organisms of the genus Candida, mainly Candida albicans (Zuccarello et al., 2002). Isolated familial chronic mucocutaneous candidiasis is distinct from candidiasis with endocrinopathy (240300). In myeloperoxidase deficiency (254600), susceptibility to candidiasis may be increased. Genetic Heterogeneity of Candidiasis Familial candidiasis-1 (CANDF1) maps to chromosome 2p. CANDF2 (212050) is caused by mutation in the CARD9 gene (607212) on chromosome 9q34.3. CANDF3 (607644), a form restricted to nails of the hands and feet, maps to chromosome 11. CANDF4 (613108) is caused by mutation in the CLEC7A gene (606264) on chromosome 12p13. CANDF6 (613956) is caused by mutation in the IL17F gene (606496) on chromosome 6p12. CANDF7 (614162) is caused by mutation in the STAT1 gene (600555) on chromosome 2q32. CANDF8 (615527) is caused by mutation in the TRAF3IP2 gene (607043) on chromosome 6q21. CANDF9 (616445) is caused by mutation in the IL17RC gene (610925) on chromosome 3p25. A form of familial candidiasis, previously thought to be isolated and designated CANDF5, has been found to be part of a primary immune deficiency (IMD51; 613953) that includes Staphylococcal skin infections and increased susceptibility to chronic bacterial respiratory infections.
Ectodermal dysplasia-syndactyly syndrome 1
MedGen UID:
462157
Concept ID:
C3150807
Disease or Syndrome
Ectodermal dysplasia-syndactyly syndrome (EDSS) is characterized by sparse to absent scalp hair, eyebrows, and eyelashes, hypoplastic nails, tooth enamel hypoplasia, conical-shaped teeth, palmoplantar keratoderma, and partial cutaneous syndactyly (summary by Raza et al., 2015). Genetic Heterogeneity of Ectodermal Dysplasia-Syndactyly Syndrome Ectodermal dysplasia-syndactyly syndrome-2 (EDSS2; 613576) maps to chromosome 7p21-p14.
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).
Adams-Oliver syndrome 2
MedGen UID:
481812
Concept ID:
C3280182
Disease or Syndrome
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
MedGen UID:
482833
Concept ID:
C3281203
Neoplastic Process
Patients with this syndrome 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).
Hemochromatosis type 1
MedGen UID:
854011
Concept ID:
C3469186
Disease or Syndrome
HFE hemochromatosis is characterized by inappropriately high absorption of iron by the small intestinal mucosa. The phenotypic spectrum of HFE hemochromatosis includes: Persons with clinical HFE hemochromatosis, in whom manifestations of end-organ damage secondary to iron overload are present; Individuals with biochemical HFE hemochromatosis, in whom transferrin-iron saturation is increased and the only evidence of iron overload is increased serum ferritin concentration; and Non-expressing p.Cys282Tyr homozygotes, in whom neither clinical manifestations of HFE hemochromatosis nor iron overload are present. Clinical HFE hemochromatosis is characterized by excessive storage of iron in the liver, skin, pancreas, heart, joints, and anterior pituitary gland. In untreated individuals, early symptoms include: abdominal pain, weakness, lethargy, weight loss, arthralgias, diabetes mellitus; and increased risk of cirrhosis when the serum ferritin is higher than 1,000 ng/mL. Other findings may include progressive increase in skin pigmentation, congestive heart failure, and/or arrhythmias, arthritis, and hypogonadism. Clinical HFE hemochromatosis is more common in men than women.
Cortisone reductase deficiency 1
MedGen UID:
764630
Concept ID:
C3551716
Disease or Syndrome
Cortisone reductase deficiency (CRD) results from a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase (HSD11B1; 600713). The oxoreductase activity of 11-beta-HSD requires the NADPH-regenerating enzyme hexose-6-phosphate dehydrogenase (H6PD; 138090) within the endoplasmic reticulum. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting in midlife with hirsutism, oligomenorrhea, and infertility. Biochemically, CRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the tetrahydrocortisol (THF) plus 5-alpha-THF/tetrahydrocortisone (THE) ratio, which in CRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lavery et al., 2008). Genetic Heterogeneity of Cortisone Reductase Deficiency CORTRD2 (614662) is caused by mutation in the HSD11B1 gene (600713) on chromosome 1q32.
Ectodermal dysplasia 6, hair/nail type
MedGen UID:
767025
Concept ID:
C3554111
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.
Ectodermal dysplasia 7, hair/nail type
MedGen UID:
767031
Concept ID:
C3554117
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.
Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
MedGen UID:
816258
Concept ID:
C3809928
Disease or Syndrome
Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
L-ferritin deficiency
MedGen UID:
816420
Concept ID:
C3810090
Disease or Syndrome
A rare genetic haematologic disease characterised by decreased or undetectable serum L-ferritin with otherwise normal laboratory parameters. Clinical signs and symptoms include generalised seizures, atypical restless leg syndrome, mild neuropsychologic impairment and progressive hair loss. Asymptomatic cases have also been reported.
Hereditary sclerosing poikiloderma with tendon and pulmonary involvement
MedGen UID:
816655
Concept ID:
C3810325
Disease or Syndrome
Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is characterized by the skin findings of poikiloderma (typically beginning in the first six months and mainly localized to the face), hypohidrosis with heat intolerance, mild lymphedema of the extremities, chronic erythematous and scaly skin lesions on the extremities, sclerosis of the digits, and mild palmoplantar keratoderma. Scalp hair, eyelashes, and/or eyebrows are typically sparse. Muscle contractures are usually seen in childhood and can be present as early as age two years. The majority of affected individuals develop progressive weakness of the proximal and distal muscles of all four limbs. Some adults develop progressive interstitial pulmonary fibrosis, which can be life threatening within three to four years after respiratory symptoms appear. Other features are exocrine pancreatic insufficiency, liver impairment, hematologic abnormalities, relative short stature, and cataract.
Autosomal recessive congenital ichthyosis 2
MedGen UID:
854762
Concept ID:
C3888093
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.
Pigmented nodular adrenocortical disease, primary, 4
MedGen UID:
862862
Concept ID:
C4014425
Disease or Syndrome
Cushing syndrome is a clinical designation for the systemic signs and symptoms arising from excess cortisol production. Affected individuals typically show hypertension, impaired glucose tolerance, central obesity, osteoporosis, and sometimes depression. Corticotropin-independent Cushing syndrome results from autonomous cortisol production by the adrenal glands, often associated with adrenocortical tumors. Adrenocortical tumors are most common in adult females (summary by Cao et al., 2014; Sato et al., 2014).
Alopecia, androgenetic, 1
MedGen UID:
886756
Concept ID:
C4049090
Disease or Syndrome
Androgenetic alopecia is characterized by a loss of hair from the scalp that follows a defined pattern (Hamilton, 1951). It occurs in women as well as in men. It is caused by a shortening of the anagen (growth) phase and miniaturization of the hair follicle, which results in the formation of progressively thinner, shorter hair (Bergfeld, 1995). In men, the condition is often referred to as male pattern baldness (MPB) and appears to be androgen-dependent (Hamilton, 1942). The condition is hereditary, and follows a pattern that may be consistent with an autosomal dominant trait (Osborn, 1916). Linkage evidence for an autosomal locus on 3q26 (AGA1) has been identified (Hillmer et al., 2008). See 300710 (AGA2) for a discussion of X linkage of androgenetic alopecia. A third locus has been found on chromosome 20p11 (AGA3; 612421).
Immunodeficiency, common variable, 12
MedGen UID:
906018
Concept ID:
C4225277
Disease or Syndrome
Common variable immunodeficiency-12 with autoimmunity (CVID12) is an autosomal dominant complex immunologic disorder with multisystem involvement. CVID12 is mainly a primary immunodeficiency characterized by recurrent infections and associated with hypogammaglobulinemia. Notably, about half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. A smaller percentage of affected individuals (less than 20%) develop cancer, most commonly solid tumors, including lymphoma. Age at onset and disease severity are highly variable, even within the same family. There is also incomplete penetrance, such that mutation carriers may be asymptomatic, even if they have hypogammaglobulinemia. The gene involved, NFKB1, encodes a transcription factor that regulates the expression of target genes involved in the immune system, thus defining the phenotype as a disorder of immune dysregulation (summary by Fliegauf et al., 2015; Lorenzini et al., 2020). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
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).
Mandibulofacial dysostosis with alopecia
MedGen UID:
898794
Concept ID:
C4225349
Disease or Syndrome
A rare mandibulofacial dysostosis with the association with scalp alopecia and sparse eyebrows and eyelashes. Craniofacial dysmorphic features include zygomatic and mandibular dysplasia or hypoplasia, cleft palate, micrognathia, dental anomalies, auricular dysmorphism and eyelid anomalies among others. Patients may experience limited jaw mobility, glossoptosis, upper airway obstruction and conductive hearing loss.
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.
Autosomal dominant palmoplantar keratoderma and congenital alopecia
MedGen UID:
930338
Concept ID:
C4304669
Disease or Syndrome
Palmoplantar keratoderma and congenital alopecia-1 (PPKCA1) is a rare autosomal dominant disorder characterized by severe hyperkeratosis and congenital alopecia. Nail changes occur in some patients (summary by Castori et al., 2010). Also see PPKCA2 (212360), an autosomal recessive disorder characterized by congenital alopecia and progressive hyperkeratosis resulting in sclerodactyly, severe contractures and tapering of the digits, and pseudoainhum formation.
Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss
MedGen UID:
934598
Concept ID:
C4310631
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.
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome
MedGen UID:
1373459
Concept ID:
C4317151
Disease or Syndrome
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome is an autosomal dominant disorder characterized by these 4 features, which begin in early childhood and are progressive (summary by Moalem et al., 2015).
Bleeding disorder, platelet-type, 21
MedGen UID:
1386863
Concept ID:
C4479515
Disease or Syndrome
BDPLT21 is a hematologic disorder characterized by increased risk of bleeding resulting from a functional platelet defect. Platelets have decreased or even absent dense bodies and abnormally enlarged and fused alpha-granules, and they show defective secretion and aggregation responses to agonists. Platelets are usually enlarged, and some patients may have mild to moderate thrombocytopenia (summary by Saultier et al., 2017).
Adams-Oliver syndrome 1
MedGen UID:
1635567
Concept ID:
C4551482
Disease or Syndrome
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
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.
Linear nevus sebaceous syndrome
MedGen UID:
1646345
Concept ID:
C4552097
Disease or Syndrome
Schimmelpenning-Feuerstein-Mims syndrome, also known as linear sebaceous nevus syndrome, is characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects (summary by Happle, 1991 and Ernst et al., 2007). The linear sebaceous nevi follow the lines of Blaschko (Hornstein and Knickenberg, 1974; Bouwes Bavinck and van de Kamp, 1985). All cases are sporadic. The syndrome is believed to be caused by an autosomal dominant lethal mutation that survives by somatic mosaicism (Gorlin et al., 2001).
Hyper-IgE recurrent infection syndrome 3, autosomal recessive
MedGen UID:
1648483
Concept ID:
C4748969
Disease or Syndrome
Hyper-IgE syndrome-3 with recurrent infections (HIES3) is an autosomal recessive immunologic disorder characterized by childhood onset of atopic dermatitis, skin infections particularly with Staphylococcus aureus, recurrent sinopulmonary infections, and increased serum IgE and IgG. Patients are susceptible to bacterial and fungal infections, including chronic mucocutaneous candidiasis. Immunologic workup shows impaired differentiation of CD4+ T cells into T-helper 17 cells, decreased memory B cells, and often decreased NK cells (summary by Beziat et al., 2018). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060).
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.
Alopecia-intellectual disability syndrome 4
MedGen UID:
1713432
Concept ID:
C5394241
Disease or Syndrome
Alopecia-intellectual disability syndrome-4 (APMR4) is characterized by alopecia universalis, scaly skin, and psychomotor retardation of varying degrees (Besnard et al., 2019). For a discussion of genetic heterogeneity of alopecia-intellectual disability syndrome, see APMR1 (203650).
Mandibuloacral dysplasia with type A lipodystrophy
MedGen UID:
1757618
Concept ID:
C5399785
Disease or Syndrome
Mandibuloacral dysplasia with type A lipodystrophy (MADA) is an autosomal recessive disorder characterized by growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes. The lipodystrophy is characterized by a marked acral loss of fatty tissue with normal or increased fatty tissue in the neck and trunk. Some patients may show progeroid features. Metabolic complications can arise due to insulin resistance and diabetes (Young et al., 1971; Simha and Garg, 2002; summary by Garavelli et al., 2009). See also MAD type B (MADB; 608612), which is caused by mutation in the ZMPSTE24 gene (606480).
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.
Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies
MedGen UID:
1784590
Concept ID:
C5543375
Disease or Syndrome
Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (GKAF) is characterized by microcephaly, congenital alopecia, distinctive craniofacial features, severe congenital sensorineural hearing loss, global developmental delay, hydrocephalus, hypoplastic kidneys with renal insufficiency, genital hypoplasia, and early mortality (Ito et al., 2018).
VISS syndrome
MedGen UID:
1794165
Concept ID:
C5561955
Disease or Syndrome
VISS syndrome is a generalized connective tissue disorder characterized by early-onset thoracic aortic aneurysm and other connective tissue findings, such as aneurysm and tortuosity of other arteries, joint hypermobility, skin laxity, and hernias, as well as craniofacial dysmorphic features, structural cardiac defects, skeletal anomalies, and motor developmental delay (Van Gucht et al., 2021). Immune dysregulation has been observed in some patients (Ziegler et al., 2021).
Systemic lupus erythematosus 17
MedGen UID:
1804329
Concept ID:
C5676884
Disease or Syndrome
Systemic lupus erythematosus-17 (SLE17) is an X-linked dominant autoimmune disorder characterized by onset of systemic autoinflammatory symptoms in the first decades of life. Only affected females have been reported. Features may include classic features of SLE, such as malar rash and arthralgias, or can include less common entities such as hemiplegia and neuromyelitis optica (NMO). Laboratory studies show the presence of autoantibodies and enhanced NFKB (164011) signaling, the latter being consistent with a gain-of-function effect (Brown et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Kury-Isidor syndrome
MedGen UID:
1807460
Concept ID:
C5676925
Disease or Syndrome
Kury-Isidor syndrome (KURIS) is a neurodevelopmental disorder with a highly variable phenotype. It is characterized mainly by mild global developmental delay apparent from infancy or early childhood with walking delayed by a few years and speech delay, often with language deficits. Intellectual development may be mildly delayed, borderline, or even normal; most patients have behavioral problems, including autism. Additional variable systemic features may include poor overall growth, hypotonia, distal skeletal anomalies, seizures, and nonspecific dysmorphic facial features (summary by Kury 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).

Professional guidelines

PubMed

Zhou C, Li X, Wang C, Zhang J
Clin Rev Allergy Immunol 2021 Dec;61(3):403-423. Epub 2021 Aug 17 doi: 10.1007/s12016-021-08883-0. PMID: 34403083
Sterkens A, Lambert J, Bervoets A
Clin Exp Med 2021 May;21(2):215-230. Epub 2021 Jan 1 doi: 10.1007/s10238-020-00673-w. PMID: 33386567
Starace M, Orlando G, Alessandrini A, Piraccini BM
Am J Clin Dermatol 2020 Feb;21(1):69-84. doi: 10.1007/s40257-019-00479-x. PMID: 31677111

Recent clinical studies

Etiology

Zhou C, Li X, Wang C, Zhang J
Clin Rev Allergy Immunol 2021 Dec;61(3):403-423. Epub 2021 Aug 17 doi: 10.1007/s12016-021-08883-0. PMID: 34403083
Bertoli MJ, Sadoughifar R, Schwartz RA, Lotti TM, Janniger CK
Dermatol Ther 2020 Nov;33(6):e14055. Epub 2020 Aug 31 doi: 10.1111/dth.14055. PMID: 32700775
Adil A, Godwin M
J Am Acad Dermatol 2017 Jul;77(1):136-141.e5. Epub 2017 Apr 7 doi: 10.1016/j.jaad.2017.02.054. PMID: 28396101
Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, Sansone A, Lombardo F
Endocrine 2017 Jul;57(1):9-17. Epub 2017 Mar 28 doi: 10.1007/s12020-017-1280-y. PMID: 28349362
Vañó-Galván S, Camacho F
Actas Dermosifiliogr 2017 Apr;108(3):221-228. Epub 2017 Jan 3 doi: 10.1016/j.ad.2016.11.010. PMID: 28061966

Diagnosis

Zhou C, Li X, Wang C, Zhang J
Clin Rev Allergy Immunol 2021 Dec;61(3):403-423. Epub 2021 Aug 17 doi: 10.1007/s12016-021-08883-0. PMID: 34403083
Alessandrini A, Bruni F, Piraccini BM, Starace M
J Eur Acad Dermatol Venereol 2021 Mar;35(3):629-640. Epub 2021 Jan 8 doi: 10.1111/jdv.17079. PMID: 33290611
Afford R, Leung AKC, Lam JM
Curr Pediatr Rev 2021;17(1):45-54. doi: 10.2174/1573396316666200430084825. PMID: 32351186
Bertoli MJ, Sadoughifar R, Schwartz RA, Lotti TM, Janniger CK
Dermatol Ther 2020 Nov;33(6):e14055. Epub 2020 Aug 31 doi: 10.1111/dth.14055. PMID: 32700775
Juárez-Rendón KJ, Rivera Sánchez G, Reyes-López MÁ, García-Ortiz JE, Bocanegra-García V, Guardiola-Avila I, Altamirano-García ML
Arch Argent Pediatr 2017 Dec 1;115(6):e404-e411. doi: 10.5546/aap.2017.eng.e404. PMID: 29087123

Therapy

Sardana K, Sachdeva S
J Cosmet Dermatol 2022 Jan;21(1):85-98. Epub 2021 Sep 26 doi: 10.1111/jocd.14436. PMID: 34564936
York K, Meah N, Bhoyrul B, Sinclair R
Expert Opin Pharmacother 2020 Apr;21(5):603-612. Epub 2020 Feb 17 doi: 10.1080/14656566.2020.1721463. PMID: 32066284
Leung AKC, Hon KL, Leong KF, Barankin B, Lam JM
Recent Pat Inflamm Allergy Drug Discov 2020;14(1):58-68. doi: 10.2174/1872213X14666200106145624. PMID: 31906842
Adil A, Godwin M
J Am Acad Dermatol 2017 Jul;77(1):136-141.e5. Epub 2017 Apr 7 doi: 10.1016/j.jaad.2017.02.054. PMID: 28396101
Hou A, Cohen B, Haimovic A, Elbuluk N
Dermatol Surg 2017 Mar;43(3):321-339. doi: 10.1097/DSS.0000000000000924. PMID: 27755171

Prognosis

Griggs J, Burroway B, Tosti A
J Am Acad Dermatol 2021 Nov;85(5):1267-1273. Epub 2019 Aug 12 doi: 10.1016/j.jaad.2019.08.018. PMID: 31415838
Filotico R, Mastrandrea V
G Ital Dermatol Venereol 2018 Apr;153(2):216-229. Epub 2018 Jan 24 doi: 10.23736/S0392-0488.18.05929-1. PMID: 29368845
Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J
J Am Acad Dermatol 2018 Jan;78(1):1-12. doi: 10.1016/j.jaad.2017.04.1141. PMID: 29241771
Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF
JAMA Dermatol 2017 Jun 1;153(6):600-602. doi: 10.1001/jamadermatol.2017.0001. PMID: 28355451Free PMC Article
Gladman DD, Ibañez D, Urowitz MB
J Rheumatol 2002 Feb;29(2):288-91. PMID: 11838846

Clinical prediction guides

Gomes TF, Soares RO
J Dtsch Dermatol Ges 2023 Jan;21(1):19-25. Epub 2023 Jan 23 doi: 10.1111/ddg.14940. PMID: 36688435
Gómez-Quispe H, Muñoz Moreno-Arrones O, Hermosa-Gelbard Á, Vañó-Galván S, Saceda-Corralo D
Actas Dermosifiliogr 2023 Jan;114(1):25-32. Epub 2022 Sep 5 doi: 10.1016/j.ad.2022.08.018. PMID: 36067826
King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, Hordinsky M, Dutronc Y, Wu WS, McCollam J, Chiasserini C, Yu G, Stanley S, Holzwarth K, DeLozier AM, Sinclair R; BRAVE-AA Investigators
N Engl J Med 2022 May 5;386(18):1687-1699. Epub 2022 Mar 26 doi: 10.1056/NEJMoa2110343. PMID: 35334197
Guttman-Yassky E, Pavel AB, Diaz A, Zhang N, Del Duca E, Estrada Y, King B, Banerjee A, Banfield C, Cox LA, Dowty ME, Page K, Vincent MS, Zhang W, Zhu L, Peeva E
J Allergy Clin Immunol 2022 Apr;149(4):1318-1328. Epub 2021 Dec 1 doi: 10.1016/j.jaci.2021.10.036. PMID: 34863853
Afford R, Leung AKC, Lam JM
Curr Pediatr Rev 2021;17(1):45-54. doi: 10.2174/1573396316666200430084825. PMID: 32351186

Recent systematic reviews

Barton VR, Toussi A, Awasthi S, Kiuru M
J Am Acad Dermatol 2022 Jun;86(6):1318-1334. Epub 2021 Apr 30 doi: 10.1016/j.jaad.2021.04.077. PMID: 33940103Free PMC Article
Fukumoto T, Fukumoto R, Magno E, Oka M, Nishigori C, Horita N
Dermatol Ther 2021 May;34(3):e14916. Epub 2021 Mar 4 doi: 10.1111/dth.14916. PMID: 33631058
Lee SW, Juhasz M, Mobasher P, Ekelem C, Mesinkovska NA
J Drugs Dermatol 2018 Apr 1;17(4):457-463. PMID: 29601622Free PMC Article
Adil A, Godwin M
J Am Acad Dermatol 2017 Jul;77(1):136-141.e5. Epub 2017 Apr 7 doi: 10.1016/j.jaad.2017.02.054. PMID: 28396101
Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, Sansone A, Lombardo F
Endocrine 2017 Jul;57(1):9-17. Epub 2017 Mar 28 doi: 10.1007/s12020-017-1280-y. PMID: 28349362

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