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Thick eyebrow

MedGen UID:
377914
Concept ID:
C1853487
Finding
Synonyms: Bushy eyebrows; Heavy eyebrows; Hypertrichosis of the eyebrows; Prominent eyebrows; Thick eyebrows
 
HPO: HP:0000574

Definition

Increased density/number and/or increased diameter of eyebrow hairs. [from HPO]

Conditions with this feature

Fucosidosis
MedGen UID:
5288
Concept ID:
C0016788
Disease or Syndrome
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Fucosidosis has been classified into 2 major types. Type 1 is characterized by rapid psychomotor regression and severe neurologic deterioration beginning at about 6 months of age, elevated sweat sodium chloride, and death within the first decade of life. Type 2 is characterized by milder psychomotor retardation and neurologic signs, the development of angiokeratoma corporis diffusum, normal sweat salinity, and longer survival (Kousseff et al., 1976).
Langer-Giedion syndrome
MedGen UID:
6009
Concept ID:
C0023003
Disease or Syndrome
Trichorhinophalangeal syndrome (TRPS) comprises TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). Both types of TRPS are characterized by distinctive facial features; ectodermal features (fine, sparse, depigmented, and slow growing hair; dystrophic nails; and small breasts); and skeletal findings (short stature; short feet; brachydactyly with ulnar or radial deviation of the fingers; and early, marked hip dysplasia). TRPS II is characterized by multiple osteochondromas (typically first observed clinically on the scapulae and around the elbows and knees between ages 1 month and 6 years) and an increased risk of mild-to-moderate intellectual disability.
Deficiency of alpha-mannosidase
MedGen UID:
7467
Concept ID:
C0024748
Disease or Syndrome
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. Three major clinical subtypes have been suggested: A mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1). A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2). A severe form manifested as prenatal loss or early death from progressive central nervous system involvement or infection (type 3). Individuals with a milder phenotype have mild-to-moderate intellectual disability, impaired hearing, characteristic coarse features, clinical or radiographic skeletal abnormalities, immunodeficiency, and primary central nervous system disease – mainly cerebellar involvement causing ataxia. Periods of psychiatric symptoms are common. Associated medical problems can include corneal opacities, hepatosplenomegaly, aseptic destructive arthritis, and metabolic myopathy. Alpha-mannosidosis is insidiously progressive; some individuals may live into the sixth decade.
Multiple endocrine neoplasia type 2B
MedGen UID:
9959
Concept ID:
C0025269
Neoplastic Process
Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, FMTC (familial medullary thyroid carcinoma, which may be a variant of MEN2A), and MEN2B. All three phenotypes involve high risk for development of medullary carcinoma of the thyroid (MTC); MEN2A and MEN2B involve an increased risk for pheochromocytoma; MEN2A involves an increased risk for parathyroid adenoma or hyperplasia. Additional features in MEN2B include mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and a marfanoid habitus. MTC typically occurs in early childhood in MEN2B, early adulthood in MEN2A, and middle age in FMTC.
Mucopolysaccharidosis type 7
MedGen UID:
43108
Concept ID:
C0085132
Disease or Syndrome
Mucopolysaccharidosis type VII (MPS7) is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved.
Mucopolysaccharidosis, MPS-III-D
MedGen UID:
88602
Concept ID:
C0086650
Disease or Syndrome
Mucopolysaccharidosis type III (MPS III) is a multisystem lysosomal storage disease characterized by progressive central nervous system degeneration manifest as severe intellectual disability (ID), developmental regression, and other neurologic manifestations including autism spectrum disorder (ASD), behavioral problems, and sleep disturbances. Disease onset is typically before age ten years. Disease course may be rapidly or slowly progressive; some individuals with an extremely attenuated disease course present in mid-to-late adulthood with early-onset dementia with or without a history of ID. Systemic manifestations can include musculoskeletal problems (joint stiffness, contractures, scoliosis, and hip dysplasia), hearing loss, respiratory tract and sinopulmonary infections, and cardiac disease (valvular thickening, defects in the cardiac conduction system). Neurologic decline is seen in all affected individuals; however, clinical severity varies within and among the four MPS III subtypes (defined by the enzyme involved) and even among members of the same family. Death usually occurs in the second or third decade of life secondary to neurologic regression or respiratory tract infections.
KBG syndrome
MedGen UID:
66317
Concept ID:
C0220687
Disease or Syndrome
KBG syndrome is typically characterized by macrodontia (especially of the upper central incisors), characteristic facial features (triangular face, brachycephaly, synophrys, widely spaced eyes, broad or bushy eyebrows, prominent ears, prominent nasal bridge, bulbous nose, anteverted nares, long philtrum, and thin vermilion of the upper lip), short stature, developmental delay / intellectual disability, and behavioral issues. Affected individuals may have feeding difficulties (particularly in infancy), skeletal anomalies (brachydactyly, large anterior fontanelle with delayed closure, scoliosis), hearing loss (conductive, mixed, and sensorineural), seizure disorder, and brain malformations. There is significant variability in the clinical findings, even between affected members of the same family.
Marshall-Smith syndrome
MedGen UID:
75551
Concept ID:
C0265211
Disease or Syndrome
The Marshall-Smith syndrome (MRSHSS) is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., 2005).
Cohen syndrome
MedGen UID:
78539
Concept ID:
C0265223
Congenital Abnormality
Cohen syndrome is characterized by failure to thrive in infancy and childhood; truncal obesity in the teen years; early-onset hypotonia and developmental delays; microcephaly developing during the first year of life; moderate to profound psychomotor retardation; progressive retinochoroidal dystrophy and high myopia; neutropenia in many with recurrent infections and aphthous ulcers in some; a cheerful disposition; joint hypermobility; and characteristic facial features.
Coffin-Lowry syndrome
MedGen UID:
75556
Concept ID:
C0265252
Disease or Syndrome
Coffin-Lowry syndrome (CLS) is usually characterized by severe-to-profound intellectual disability in males; less severely impaired individuals have been reported. Neuropsychiatric concerns can include behavioral problems, loss of strength, progressive spasticity or paraplegia, sleep apnea, or stroke. Stimulus-induced drop attacks (SIDAs) in which unexpected tactile or auditory stimuli or excitement triggers a brief collapse but no loss of consciousness are present in approximately 20% of affected individuals. Typically SIDAs begin between mid-childhood and the teens. Characteristic facial features may be more apparent with age. Upper-extremity differences may be subtle and include short, soft, fleshy hands with tapered fingers as well as fleshy forearms. Progressive kyphoscoliosis is one of the most difficult aspects of long-term care. Affected females tend to have intellectual disability in the mild-to-moderate range and may also have the typical facial, hand, and skeletal findings noted in males.
Myhre syndrome
MedGen UID:
167103
Concept ID:
C0796081
Disease or Syndrome
Myhre syndrome is a connective tissue disorder with multisystem involvement, progressive and proliferative fibrosis that may occur spontaneously or following trauma or surgery, mild-to-moderate intellectual disability, and in some instances, autistic-like behaviors. Organ systems primarily involved include: cardiovascular (congenital heart defects, long- and short-segment stenosis of the aorta and peripheral arteries, pericardial effusion, constrictive pericarditis, restrictive cardiomyopathy, and hypertension); respiratory (choanal stenosis, laryngotracheal narrowing, obstructive airway disease, or restrictive pulmonary disease), gastrointestinal (pyloric stenosis, duodenal strictures, severe constipation); and skin (thickened particularly on the hands and extensor surfaces). Additional findings include distinctive craniofacial features and skeletal involvement (intrauterine growth restriction, short stature, limited joint range of motion). To date, 55 individuals with molecularly confirmed Myhre syndrome have been reported.
Elsahy-Waters syndrome
MedGen UID:
923028
Concept ID:
C0809936
Disease or Syndrome
The core phenotype of Elsahy-Waters syndrome consists of brachycephaly, facial asymmetry, marked hypertelorism, proptosis, blepharochalasis, midface hypoplasia, broad nose with concave nasal ridge, and prognathism; radicular dentin dysplasia with consequent obliterated pulp chambers, apical translucent cysts, recurrent infections, and early loss of teeth; vertebral fusions, particularly at C2-C3; and moderate mental retardation. Skin wrinkling over the glabellar region seems common, and in males, hypospadias has always been present. Inter- and intrafamilial variability has been reported regarding the presence of vertebral fusions, hearing loss, and dentigerous cysts. Midface hypoplasia, facial asymmetry, progressive dental anomalies, and impaired cognitive development become more evident in adulthood (summary by Castori et al., 2010).
Hajdu-Cheney syndrome
MedGen UID:
182961
Concept ID:
C0917715
Disease or Syndrome
Hajdu-Cheney syndrome (HJCYS) is a rare autosomal dominant skeletal disorder characterized by short stature, coarse and dysmorphic facies, bowing of the long bones, and vertebral anomalies. Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. There is progressive focal bone destruction, including acroosteolysis and generalized osteoporosis. Additional and variable features include hearing loss, renal cysts, and cardiovascular anomalies (summary by Ramos et al., 1998; Simpson et al., 2011; Isidor et al., 2011).
Congenital muscular hypertrophy-cerebral syndrome
MedGen UID:
315658
Concept ID:
C1802395
Disease or Syndrome
Cornelia de Lange syndrome (CdLS) encompasses a spectrum of findings from mild to severe. Severe (classic) CdLS is characterized by distinctive facial features, growth restriction (prenatal onset; <5th centile throughout life), hypertrichosis, and upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, highly arched and/or thick eyebrows, long eyelashes, short nasal bridge with anteverted nares, small widely spaced teeth, and microcephaly. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS. Across the CdLS spectrum IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Other frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia.
Goldberg-Shprintzen syndrome
MedGen UID:
332131
Concept ID:
C1836123
Disease or Syndrome
Goldberg-Shprintzen syndrome (GOSHS) is an autosomal recessive multiple congenital anomaly syndrome characterized by impaired intellectual development, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease and/or gyral abnormalities of the brain, consistent with defects in migration of neural crest cells and neurons. Other features, such as megalocornea or urogenital anomalies, may also be present. Goldberg-Shprintzen syndrome has some resemblance to Mowat-Wilson syndrome (MOWS; 235730) but is genetically distinct (summary by Drevillon et al., 2013).
Wilson-Turner syndrome
MedGen UID:
333393
Concept ID:
C1839736
Disease or Syndrome
Wilson-Turner syndrome (WTS) is an X-linked recessive neurologic disorder characterized by intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Females are unaffected (Wilson et al., 1991).
Syndromic X-linked intellectual disability Claes-Jensen type
MedGen UID:
335139
Concept ID:
C1845243
Disease or Syndrome
Claes-Jensen type of X-linked syndromic intellectual developmental disorder (MRXSCJ) is characterized by impaired intellectual development with substantial clinical heterogeneity in affected males. However, males are usually reported to have short stature, microcephaly, hyperreflexia, and aggressive behavior. In rare cases, female carriers exhibit mildly impaired intellectual development or learning difficulties (summary by Guerra et al., 2020).
Uruguay Faciocardiomusculoskeletal syndrome
MedGen UID:
335320
Concept ID:
C1846010
Disease or Syndrome
Uruguay faciocardiomusculoskeletal syndrome (FCMSU) is an X-linked disorder in which affected males have a distinctive facial appearance, muscular hypertrophy, and cardiac ventricular hypertrophy leading to premature death. Additional features include large, broad, and deformed hands and feet, congenital hip dislocation, and scoliosis (summary by Xue et al., 2016).
Spondyloepimetaphyseal dysplasia, Bieganski type
MedGen UID:
335350
Concept ID:
C1846148
Disease or Syndrome
X-linked spondyloepimetaphyseal dysplasia with hypomyelinating leukodystrophy (SEMDHL) is an X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy (summary by Miyake et al., 2017).
Oculofaciocardiodental syndrome
MedGen UID:
337547
Concept ID:
C1846265
Disease or Syndrome
Oculofaciocardiodental (OFCD) syndrome is a condition that affects the development of the eyes (oculo-), facial features (facio-), heart (cardio-) and teeth (dental). This condition occurs only in females.\n\nThe eye abnormalities associated with OFCD syndrome can affect one or both eyes. Many people with this condition are born with eyeballs that are abnormally small (microphthalmia). Other eye problems can include clouding of the lens (cataract) and a higher risk of glaucoma, an eye disease that increases the pressure in the eye. These abnormalities can lead to vision loss or blindness.\n\nPeople with OFCD syndrome often have a long, narrow face with distinctive facial features, including deep-set eyes and a broad nasal tip that is divided by a cleft. Some affected people have an opening in the roof of the mouth called a cleft palate.\n\nHeart defects are another common feature of OFCD syndrome. Babies with this condition may be born with a hole between two chambers of the heart (an atrial or ventricular septal defect) or a leak in one of the valves that controls blood flow through the heart (mitral valve prolapse).\n\nTeeth with very large roots (radiculomegaly) are characteristic of OFCD syndrome. Additional dental abnormalities can include delayed loss of primary (baby) teeth, missing or abnormally small teeth, misaligned teeth, and defective tooth enamel.
Waardenburg syndrome type 1
MedGen UID:
376211
Concept ID:
C1847800
Disease or Syndrome
Waardenburg syndrome type I (WS1) is an auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin along with dystopia canthorum (lateral displacement of the inner canthi). The hearing loss in WS1, observed in approximately 60% of affected individuals, is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural. Most commonly, hearing loss in WS1 is bilateral and profound (>100 dB). The majority of individuals with WS1 have either a white forelock or early graying of the scalp hair before age 30 years. The classic white forelock observed in approximately 45% of individuals is the most common hair pigmentation anomaly seen in WS1. Affected individuals may have complete heterochromia iridium, partial/segmental heterochromia, or hypoplastic or brilliant blue irides. Congenital leukoderma is frequently seen on the face, trunk, or limbs.
Growth delay due to insulin-like growth factor I resistance
MedGen UID:
338622
Concept ID:
C1849157
Disease or Syndrome
Patients with mutations in the receptor for insulin-like growth factor I show intrauterine growth retardation and postnatal growth failure, resulting in short stature and microcephaly. Other features may include delayed bone age, developmental delay, and dysmorphic features.
Cornelia de Lange syndrome 3
MedGen UID:
339902
Concept ID:
C1853099
Disease or Syndrome
Cornelia de Lange syndrome (CdLS) encompasses a spectrum of findings from mild to severe. Severe (classic) CdLS is characterized by distinctive facial features, growth restriction (prenatal onset; <5th centile throughout life), hypertrichosis, and upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, highly arched and/or thick eyebrows, long eyelashes, short nasal bridge with anteverted nares, small widely spaced teeth, and microcephaly. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS. Across the CdLS spectrum IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Other frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia.
Intellectual disability, microcephaly, growth retardation, joint contractures, and facial dysmorphism
MedGen UID:
342889
Concept ID:
C1853480
Disease or Syndrome
Phelan-McDermid syndrome
MedGen UID:
339994
Concept ID:
C1853490
Disease or Syndrome
Phelan-McDermid syndrome is characterized by neonatal hypotonia, absent to severely delayed speech, developmental delay, and minor dysmorphic facial features. Most affected individuals have moderate to profound intellectual disability. Other features include large fleshy hands, dysplastic toenails, and decreased perspiration that results in a tendency to overheat. Normal stature and normal head size distinguishes Phelan-McDermid syndrome from other autosomal chromosome disorders. Behavior characteristics include mouthing or chewing non-food items, decreased perception of pain, and autism spectrum disorder or autistic-like affect and behavior.
Wiedemann-Steiner syndrome
MedGen UID:
340266
Concept ID:
C1854630
Disease or Syndrome
Wiedemann-Steiner syndrome (WSS) is characterized by developmental delay, intellectual disability, and characteristic facial features, with or without additional congenital anomalies. The facial features include thick eyebrows with lateral flare, vertically narrow and downslanted palpebral fissures, widely spaced eyes, long eyelashes, wide nasal bridge, broad nasal tip, thin vermilion of the upper lip, and thick scalp hair. About 60% of affected individuals have hypertrichosis cubiti ("hairy elbows"), which was once thought to be pathognomic for the syndrome, with a majority having hypertrichosis of other body parts. Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical spine), renal and uterine anomalies, immune dysfunction, brain malformations, and dental anomalies.
Microcephaly 4, primary, autosomal recessive
MedGen UID:
347655
Concept ID:
C1858516
Disease or Syndrome
Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (summary by Woods et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome
MedGen UID:
347880
Concept ID:
C1859432
Disease or Syndrome
A rare syndrome characterised by the association of blepharophimosis and ptosis, V-esotropia, and weakness of extraocular and frontal muscles with syndactyly of the toes, short stature, prognathism, and hypertrophy and fusion of the eyebrows.
Mandibulofacial dysostosis-macroblepharon-macrostomia syndrome
MedGen UID:
355927
Concept ID:
C1865181
Disease or Syndrome
Mandibulofacial dysostosis-macroblepharon-macrostomia syndrome is a rare developmental defect during embryogenesis disorder characterized by macroblepharon, ectropion, and facial dysmorphism which includes severe hypertelorism, downslanting palpebral fissures, posteriorly rotated ears, broad nasal bridge, long and smooth philtrum, and macrostomia with thin upper lip vermilion border. Other features may include large fontanelles, prominent metopic ridge, thick eyebrows, mild synophrys, increased density of upper eyelashes, anterverted nares, abnormal dentition and capillary hemangioma.
Char syndrome
MedGen UID:
358356
Concept ID:
C1868570
Disease or Syndrome
Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus, and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are depressed nasal bridge and broad flat nasal tip, widely spaced eyes, downslanted palpebral fissures, mild ptosis, short philtrum with prominent philtral ridges with an upward pointing vermilion border resulting in a triangular mouth, and thickened (patulous) everted lips. Less common findings include other types of congenital heart defects, other hand and foot anomalies, hypodontia, hearing loss, myopia and/or strabismus, polythelia, parasomnia, craniosynostosis (involving either the metopic or sagittal suture), and short stature.
Intellectual disability, autosomal dominant 1
MedGen UID:
409857
Concept ID:
C1969562
Mental or Behavioral Dysfunction
MBD5 haploinsufficiency is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, severe speech impairment, seizures, sleep disturbances, and abnormal behaviors. Most children lack speech entirely or have single words, short phrases, or short sentences. Seizures are present in more than 80% of children; onset is usually around age two years. Sleep disturbances, present in about 90%, can result in excessive daytime drowsiness. Abnormal behaviors can include autistic-like behaviors (80%) and self-injury and aggression (>60%).
Intellectual disability, autosomal recessive 5
MedGen UID:
370849
Concept ID:
C1970199
Mental or Behavioral Dysfunction
Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the NSUN2 gene.
Christianson syndrome
MedGen UID:
394455
Concept ID:
C2678194
Disease or Syndrome
Christianson syndrome (referred to as CS in this GeneReview), an X-linked disorder, is characterized in males by cognitive dysfunction, behavioral disorder, and neurologic findings (e.g., seizures, ataxia, postnatal microcephaly, and eye movement abnormalities). Males with CS typically present with developmental delay, later meeting criteria for severe intellectual disability (ID). Behaviorally, autism spectrum disorder and hyperactivity are common, and may resemble the behaviors observed in Angelman syndrome. Hypotonia and oropharyngeal dysphagia in infancy may result in failure to thrive. Seizures, typically beginning before age three years, can include infantile spasms and tonic, tonic-clonic, myoclonic, and atonic seizures. Subsequently, regression (e.g., loss of ambulation and ability to feed independently) may occur. Manifestations in heterozygous females range from asymptomatic to mild ID and/or behavioral issues.
3M syndrome 1
MedGen UID:
395592
Concept ID:
C2678312
Disease or Syndrome
Three M syndrome is characterized by severe pre- and postnatal growth deficiency (final height 5-6 SD below the mean; i.e., 120-130 cm), characteristic facies, and normal intelligence. Additional features of three M syndrome include short broad neck, prominent trapezii, deformed sternum, short thorax, square shoulders, winged scapulae, hyperlordosis, short fifth fingers, prominent heels, and loose joints. Males with three M syndrome have hypogonadism and occasionally hypospadias.
Chromosome Xp11.23-p11.22 duplication syndrome
MedGen UID:
440690
Concept ID:
C2749022
Disease or Syndrome
Familial and <i>de novo</i> recurrent Xp11.22-p11.23 microduplication has been recently identified in males and females.
BNAR syndrome
MedGen UID:
413305
Concept ID:
C2750433
Disease or Syndrome
FREM1 autosomal recessive disorders include: Manitoba oculotrichoanal (MOTA) syndrome, bifid nose with or without anorectal and renal anomalies (BNAR syndrome), and isolated congenital anomalies of kidney and urinary tract (CAKUT). MOTA syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (widely spaced eyes, anophthalmia/microphthalmia and/or cryptophthalmos, colobomas of the upper eyelid, and corneopalpebral synechiae), nose (bifid or broad nasal tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal. BNAR syndrome is characterized by a bifid or wide nasal tip, anorectal anomalies, and renal malformations (e.g., renal agenesis, renal dysplasia). Typically the eye manifestations of MOTA syndrome are absent. FREM1-CAKUT was identified in one individual with bilateral vesicoureteral reflux (VUR) and a second individual with VUR and renal hypodysplasia.
MGAT2-congenital disorder of glycosylation
MedGen UID:
443956
Concept ID:
C2931008
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. These glycoconjugates play critical roles in metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity, among others. CDGs are divided into 2 main groups: type I CDGs (see, e.g., CDG1A, 212065) comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs refer to defects in the trimming and processing of the protein-bound glycans either late in the endoplasmic reticulum or the Golgi compartments. The biochemical changes of CDGs are most readily observed in serum transferrin (TF; 190000), and the diagnosis is usually made by isoelectric focusing of this glycoprotein (reviews by Marquardt and Denecke, 2003; Grunewald et al., 2002). Genetic Heterogeneity of Congenital Disorder of Glycosylation Type II Multiple forms of CDG type II have been identified; see CDG2B (606056) through CDG2Z (620201), and CDG2AA (620454) to CDG2BB (620546).
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
MedGen UID:
462291
Concept ID:
C3150941
Disease or Syndrome
Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal, then height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Obesity may develop in childhood or adolescence. Average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-RSTS have normal intellect. Additional features include ocular abnormalities, hearing loss, respiratory difficulties, congenital heart defects, renal abnormalities, cryptorchidism, feeding problems, recurrent infections, and severe constipation.
Larsen-like syndrome, B3GAT3 type
MedGen UID:
480034
Concept ID:
C3278404
Disease or Syndrome
CHST3-related skeletal dysplasia is characterized by short stature of prenatal onset, joint dislocations (knees, hips, radial heads), clubfeet, and limitation of range of motion that can involve all large joints. Kyphosis and occasionally scoliosis with slight shortening of the trunk develop in childhood. Minor heart valve dysplasia has been described in several persons. Intellect and vision are normal.
Holoprosencephaly 11
MedGen UID:
481845
Concept ID:
C3280215
Disease or Syndrome
Any holoprosencephaly in which the cause of the disease is a mutation in the CDON gene.
Coffin-Siris syndrome 1
MedGen UID:
482831
Concept ID:
C3281201
Disease or Syndrome
Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment.
Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome
MedGen UID:
762020
Concept ID:
C3541319
Disease or Syndrome
Among the Yakuts, an Asian population isolate that is located in the northeastern part of Siberia, Maksimova et al. (2010) ascertained an autosomal recessive short stature syndrome involving postnatal growth failure, small hands and feet, loss of visual acuity with abnormalities of color vision, abnormal nuclear shape in neutrophil granulocytes (Pelger-Huet anomaly; see 169400), and normal intelligence.
Intellectual disability, autosomal dominant 14
MedGen UID:
766161
Concept ID:
C3553247
Disease or Syndrome
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with ARID1A mutations have a wide spectrum of manifestations, from severe intellectual disability and serious internal complications that could result in early death to mild intellectual disability (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). The chromosome 1p36.11 duplication syndrome, in which the ARID1A gene is duplicated, is characterized by impaired intellectual development, microcephaly, dysmorphic facial features, and hand and foot anomalies.
Intellectual disability, autosomal dominant 15
MedGen UID:
766162
Concept ID:
C3553248
Disease or Syndrome
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCB1 mutations may have more severe neurodevelopmental deficits including severe intellectual disability, brain structural abnormalities, and no expressive words, as well as scoliosis (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Intellectual disability, autosomal dominant 16
MedGen UID:
766163
Concept ID:
C3553249
Disease or Syndrome
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCA4 mutations may have less coarse craniofacial appearances and fewer behavioral abnormalities than Coffin-Siris patients with mutations in other genes (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Hypertelorism and other facial dysmorphism, brachydactyly, genital abnormalities, intellectual disability, and recurrent inflammatory episodes
MedGen UID:
766379
Concept ID:
C3553465
Disease or Syndrome
Cornelia de Lange syndrome 4
MedGen UID:
766431
Concept ID:
C3553517
Disease or Syndrome
Cornelia de Lange syndrome (CdLS) encompasses a spectrum of findings from mild to severe. Severe (classic) CdLS is characterized by distinctive facial features, growth restriction (prenatal onset; <5th centile throughout life), hypertrichosis, and upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, highly arched and/or thick eyebrows, long eyelashes, short nasal bridge with anteverted nares, small widely spaced teeth, and microcephaly. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS. Across the CdLS spectrum IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Other frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia.
Pontocerebellar hypoplasia type 8
MedGen UID:
767123
Concept ID:
C3554209
Disease or Syndrome
Pontocerebellar hypoplasia type 8 is an autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum (summary by Mochida et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
SLC35A2-congenital disorder of glycosylation
MedGen UID:
813018
Concept ID:
C3806688
Disease or Syndrome
Congenital disorder of glycosylation type IIm, or developmental and epileptic encephalopathy-22 (DEE22), is an X-linked dominant severe neurologic disorder characterized by infantile-onset seizures, hypsarrhythmia on EEG, hypotonia, and developmental delay associated with severe intellectual disability and lack of speech. These features are consistent with developmental and epileptic encephalopathy (DEE). Brain malformations usually include cerebral and cerebellar atrophy. Additionally, some patients may have dysmorphic features or coarse facies (Ng et al., 2013; Kodera et al., 2013). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Mitochondrial DNA depletion syndrome 13
MedGen UID:
815922
Concept ID:
C3809592
Disease or Syndrome
FBXL4-related encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome is a multi-system disorder characterized primarily by congenital or early-onset lactic acidosis and growth failure, feeding difficulty, hypotonia, and developmental delay. Other neurologic manifestations can include seizures, movement disorders, ataxia, autonomic dysfunction, and stroke-like episodes. All affected individuals alive at the time they were reported (median age: 3.5 years) demonstrated significant developmental delay. Other findings can involve the heart (hypertrophic cardiomyopathy, congenital heart malformations, arrhythmias), liver (mildly elevated transaminases), eyes (cataract, strabismus, nystagmus, optic atrophy), hearing (sensorineural hearing loss), and bone marrow (neutropenia, lymphopenia). Survival varies; the median age of reported deaths was two years (range 2 days – 75 months), although surviving individuals as old as 36 years have been reported. To date FBXL4-related mtDNA depletion syndrome has been reported in 50 individuals.
Autism spectrum disorder due to AUTS2 deficiency
MedGen UID:
862872
Concept ID:
C4014435
Mental or Behavioral Dysfunction
A rare genetic syndromic intellectual disability characterized by global developmental delay and borderline to severe intellectual disability, autism spectrum disorder with obsessive behavior, stereotypies, hyperactivity but frequently friendly and affable personality, feeding difficulties, short stature, muscular hypotonia, microcephaly, characteristic dysmorphic features (hypertelorism, high arched eyebrows, ptosis, deep and/or broad nasal bridge, broad/prominent nasal tip, short and/or upturned philtrum, narrow mouth, and micrognathia), and skeletal anomalies (kyphosis and/or scoliosis, arthrogryposis, slender habitus and extremities). Other clinical features may include hernias, congenital heart defects, cryptorchidism and seizures.
Developmental and epileptic encephalopathy, 23
MedGen UID:
862929
Concept ID:
C4014492
Disease or Syndrome
Developmental and epileptic encephalopathy-23 (DEE23) is an autosomal recessive neurologic disorder characterized by the onset of intractable seizures in the first months of life (range, 2-6 months). Affected individuals have severely impaired psychomotor development with poor or absent speech, cortical blindness, and dysmorphic facial features (summary by Perrault et al., 2014).
Tatton-Brown-Rahman overgrowth syndrome
MedGen UID:
862982
Concept ID:
C4014545
Disease or Syndrome
Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth / intellectual disability syndrome characterized by length/height and/or head circumference =2 SD above the mean for age and sex, obesity / increased weight, intellectual disability that ranges from mild to severe, joint hypermobility, hypotonia, behavioral/psychiatric issues, kyphoscoliosis, and seizures. Individuals with TBRS have subtle dysmorphic features, including a round face with coarse features, thick horizontal low-set eyebrows, narrow (as measured vertically) palpebral fissures, and prominent upper central incisors. The facial gestalt is most easily recognizable in the teenage years. TBRS may be associated with an increased risk of developing acute myeloid leukemia. There are less clear associations with aortic root dilatation and increased risk of other hematologic and solid tumors.
Intellectual disability, autosomal recessive 45
MedGen UID:
863301
Concept ID:
C4014864
Mental or Behavioral Dysfunction
Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the FBXO31 gene.
Cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
MedGen UID:
863379
Concept ID:
C4014942
Disease or Syndrome
CAGSSS, which comprises cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, is an autosomal recessive multisystemic disorder with a highly variable phenotypic spectrum. Not all of these features are always present, and almost all the features may present at different times and/or become more apparent with age. The skeletal features are consistent with spondyloepimetaphyseal dysplasia (SEMD) (summary by Vona et al., 2018). One family had a distinctive presentation with infantile-onset intractable seizures and cortical abnormalities reminiscent of Leigh syndrome (see 256000). The correlation between genotype and phenotype remains unclear, but since the IARS2 gene is involved in mitochondrial function, heterogeneous manifestations can be expected (Takezawa et al., 2018).
Autosomal recessive spinocerebellar ataxia 17
MedGen UID:
863738
Concept ID:
C4015301
Disease or Syndrome
Autosomal recessive spinocerebellar ataxia-17 (SCAR17) is a neurologic disorder characterized by onset of gait ataxia and cerebellar signs in early childhood. Patients also have variably impaired intellectual development (summary by Evers et al., 2016).
Tenorio syndrome
MedGen UID:
864147
Concept ID:
C4015710
Disease or Syndrome
Tenorio syndrome (TNORS) is characterized by overgrowth, macrocephaly, and impaired intellectual development. Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome (270150) (summary by Tenorio et al., 2014).
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
MedGen UID:
894554
Concept ID:
C4085597
Disease or Syndrome
CHOPS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). The name "CHOPS" is an abbreviation for a list of features of the disorder including cognitive impairment, coarse facial features, heart defects, obesity, lung (pulmonary) involvement, short stature, and skeletal abnormalities.\n\nChildren with CHOPS syndrome have intellectual disability and delayed development of skills such as sitting and walking. Characteristic facial features include a round face; thick hair; thick eyebrows that grow together in the middle (synophrys); wide-set, bulging eyes with long eyelashes; a short nose; and down-turned corners of the mouth.\n\nMost affected individuals are born with a heart defect called patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Multiple heart abnormalities have sometimes been found in children with CHOPS syndrome. In addition to PDA, affected individuals may have ventricular septal defect, which is a defect in the muscular wall (septum) that separates the right and left sides of the heart's lower chamber.\n\nPeople with CHOPS syndrome have abnormalities of the throat and airways that cause momentary cessation of breathing while asleep (obstructive sleep apnea). These abnormalities can also cause affected individuals to breathe food or fluids into the lungs accidentally, which can lead to a potentially life-threatening bacterial lung infection (aspiration pneumonia) and chronic lung disease. Affected individuals are shorter than more than 97 percent of their peers and are overweight for their height. They also have skeletal differences including unusually short fingers and toes (brachydactyly) and abnormally-shaped spinal bones (vertebrae).\n\nOther features that can occur in CHOPS syndrome include a small head size (microcephaly); hearing loss; clouding of the lens of the eye (cataract); a single, horseshoe-shaped kidney; and, in affected males, undescended testes (cryptorchidism).
Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome
MedGen UID:
902346
Concept ID:
C4225193
Disease or Syndrome
A rare genetic neurological disorder with characteristics of congenital microcephaly, severe intellectual disability, hypertonia at birth lessening with age, ataxia and specific dysmorphic facial features including hirsutism, low anterior hairline and bitemporal narrowing arched thick and medially sparse eyebrows, long eyelashes, lateral upper eyelids swelling and a skin fold partially covering the inferior eyelids, low-set posteriorly rotated protruding ears, anteverted nares and a full lower lip. Brain imaging shows partial to almost complete agenesis of the corpus callosum and variable degrees of cerebellar hypoplasia. Caused by homozygous mutation in the FRMD4A gene on chromosome 10p13.
Acrofacial dysostosis Cincinnati type
MedGen UID:
903483
Concept ID:
C4225317
Disease or Syndrome
The Cincinnati type of acrofacial dysostosis is a ribosomopathy characterized by a spectrum of mandibulofacial dysostosis phenotypes, with or without extrafacial skeletal defects (Weaver et al., 2015). In addition, a significant number of neurologic abnormalities have been reported, ranging from mild delays to refractory epilepsy, as well as an increased incidence of congenital heart defects, primarily septal in nature (Smallwood et al., 2023).
Zimmermann-Laband syndrome 2
MedGen UID:
897567
Concept ID:
C4225321
Disease or Syndrome
Any Zimmermann-Laband syndrome in which the cause of the disease is a mutation in the ATP6V1B2 gene.
Hypotonia, ataxia, and delayed development syndrome
MedGen UID:
934585
Concept ID:
C4310618
Disease or Syndrome
EBF3 neurodevelopmental disorder (EBF3-NDD) is associated with developmental delay (DD) / intellectual disability (ID), speech delay, gait or truncal ataxia, hypotonia, behavioral problems, and facial dysmorphism. Variability between individuals with EBF3-NDD is significant. Although all affected children have DD noted in early infancy, intellect generally ranges from mild to severe ID, with two individuals functioning in the low normal range. Less common issues can include genitourinary abnormalities and gastrointestinal and/or musculoskeletal involvement. To date, 42 symptomatic individuals from 39 families have been reported.
Developmental and epileptic encephalopathy, 49
MedGen UID:
934602
Concept ID:
C4310635
Disease or Syndrome
Developmental and epileptic encephalopathy-49 (DEE49) is a severe autosomal recessive neurologic disorder characterized by onset of seizures in the neonatal period, global developmental delay with intellectual disability and lack of speech, hypotonia, spasticity, and coarse facial features. Some patients may have brain calcifications on imaging (summary by Han et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Neurodevelopmental disorder with hypotonia, seizures, and absent language
MedGen UID:
934610
Concept ID:
C4310643
Disease or Syndrome
Frontometaphyseal dysplasia 2
MedGen UID:
934664
Concept ID:
C4310697
Disease or Syndrome
Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia characterized by supraorbital hyperostosis, undermodeling of the small bones, and small and large joint contractures, as well as extraskeletal developmental abnormalities, primarily of the cardiorespiratory system and genitourinary tract. Patients with FMD2 appear to have a propensity for keloid formation (summary by Wade et al., 2016). For a discussion of genetic heterogeneity of frontometaphyseal dysplasia, see FMD1 (305620).
Alazami-Yuan syndrome
MedGen UID:
934669
Concept ID:
C4310702
Disease or Syndrome
Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
MedGen UID:
934707
Concept ID:
C4310740
Disease or Syndrome
TRIO-related intellectual disability (ID) is characterized by delay in acquisition of motor and language skills, mild to borderline intellectual disability, and neurobehavioral problems (including autistic traits or autism spectrum disorder, attention-deficit/hyperactivity disorder, and/or aggression). Neonatal or infantile feeding difficulties including poor suck, impaired bottle feeding, and failure to thrive are common and are often the presenting finding. Other findings can include microcephaly, variable hand and dental abnormalities, and suggestive facial features. Only ten of the 20 individuals with a TRIO pathogenic variant reported to date had sufficient information to make preliminary generalizations about clinical manifestations; it is anticipated that the phenotype of this newly described disorder will continue to evolve.
Intellectual disability, autosomal dominant 41
MedGen UID:
934751
Concept ID:
C4310784
Disease or Syndrome
Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the TBL1XR1 gene.
Coffin-Siris syndrome 5
MedGen UID:
934755
Concept ID:
C4310788
Disease or Syndrome
Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly (summary by Wieczorek et al., 2013). Patients with SMARCE1 mutations have a wide spectrum of manifestations, including severe to moderate intellectual disability and heart defects (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Xq25 microduplication syndrome
MedGen UID:
935016
Concept ID:
C4311049
Disease or Syndrome
Xq25 duplication syndrome is an X-linked neurodevelopmental disorder characterized by delayed development and intellectual disability associated with abnormal behavior and dysmorphic facial features. Additional variable features may include thin corpus callosum on brain imaging and sleep disturbances. Carrier females may be mildly affected (summary by Leroy et al., 2016).
Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder
MedGen UID:
1385307
Concept ID:
C4479246
Disease or Syndrome
CDK13-related disorder, reported in 43 individuals to date, is characterized in all individuals by developmental delay / intellectual disability (DD/ID); nearly all individuals older than age one year display impaired verbal language skills (either absent or restricted speech). Other common findings are recognizable facial features in some individuals, behavioral problems (autism spectrum disorder or autistic traits/stereotypies, attention-deficit/hyperactivity disorder), feeding difficulties in infancy, structural cardiac defects, and seizures.
Brachycephaly, trichomegaly, and developmental delay
MedGen UID:
1374289
Concept ID:
C4479431
Disease or Syndrome
BTDD is an autosomal dominant disorder characterized by brachycephaly, trichomegaly, and developmental delay. Although it is caused by dysfunction of the ribosome, patients do not have anemia (summary by Paolini et al., 2017).
Alkaline ceramidase 3 deficiency
MedGen UID:
1622324
Concept ID:
C4540358
Disease or Syndrome
A rare genetic disorder with characteristics of infantile onset of stagnation and regression of motor and language development resulting in complete lack of communication and purposeful movement. Further neurological manifestations include truncal hypotonia, appendicular spasticity, dystonia, optic disc pallor, peripheral neuropathy and neurogenic bladder. Patients also present multiple contractures, late-onset relative macrocephaly, short stature and facial dysmorphism (including coarse facial features, sloping forehead, thick eyebrows, low-set ears, prominent nose, flat philtrum, and prominent lower lip). Brain imaging at advanced stages shows diffuse abnormal white matter signal and severe atrophy. Sural nerve biopsy reveals decreased myelination.
Kleefstra syndrome 2
MedGen UID:
1623903
Concept ID:
C4540395
Disease or Syndrome
Kleefstra syndrome-2 (KLEFS2) is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features (summary by Koemans et al., 2017). For a discussion of genetic heterogeneity of Kleefstra syndrome, see KLEFS1 (610253).
Intellectual disability, autosomal recessive 61
MedGen UID:
1622296
Concept ID:
C4540424
Mental or Behavioral Dysfunction
MRT61 is an autosomal recessive neurodevelopmental disorder characterized by delayed psychomotor development, moderate to severe intellectual disability, and variable dysmorphic facial features. More severely affected patients may develop refractory seizures and have brain abnormalities, including hypoplasia of the corpus callosum (summary by Alwadei et al., 2016).
Zimmermann-Laband syndrome 1
MedGen UID:
1639277
Concept ID:
C4551773
Disease or Syndrome
Zimmermann-Laband syndrome is a rare disorder characterized by gingival fibromatosis, dysplastic or absent nails, hypoplasia of the distal phalanges, scoliosis, hepatosplenomegaly, hirsutism, and abnormalities of the cartilage of the nose and/or ears (summary by Balasubramanian and Parker, 2010). Genetic Heterogeneity of Zimmermann-Laband Syndrome ZLS2 (616455) is caused by mutation in the ATP6V1B2 gene (606939) on chromosome 8p21. ZLS3 (618658) is caused by mutation in the KCNN3 gene (602983) on chromosome 1q21.
Rubinstein-Taybi syndrome due to CREBBP mutations
MedGen UID:
1639327
Concept ID:
C4551859
Disease or Syndrome
Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal, then height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Obesity may develop in childhood or adolescence. Average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-RSTS have normal intellect. Additional features include ocular abnormalities, hearing loss, respiratory difficulties, congenital heart defects, renal abnormalities, cryptorchidism, feeding problems, recurrent infections, and severe constipation.
Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features
MedGen UID:
1647077
Concept ID:
C4693405
Disease or Syndrome
Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (NEDMAGA) is characterized by infantile-onset global developmental delay with severe to profound intellectual disability, mildly delayed walking with broad-based and unsteady gait, and absence of meaningful language. Patients have features of autism, with repetitive behaviors and poor communication, but usually are socially reactive and have a happy demeanor. More variable neurologic features include mild seizures, spasticity, and peripheral neuropathy (summary by Palmer et al., 2017).
Developmental and epileptic encephalopathy, 63
MedGen UID:
1646846
Concept ID:
C4693810
Disease or Syndrome
Developmental and epileptic encephalopathy-63 (DEE63) is an autosomal recessive neurologic disorder characterized by early-onset refractory infantile spasms and myoclonic seizures in the first months to years of life. Affected individuals have severe to profound developmental delay, often with hypotonia and inability to sit or speak (summary by Redler et al., 2017). For a discussion of genetic heterogeneity of DEE, see 308350.
PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome
MedGen UID:
1641154
Concept ID:
C4693860
Disease or Syndrome
Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity. The severity of the phenotype and additional features are variable (summary by Jansen et al., 2018).
Developmental and epileptic encephalopathy, 64
MedGen UID:
1633501
Concept ID:
C4693899
Disease or Syndrome
Developmental and epileptic encephalopathy-64 (DEE64) is a neurodevelopmental disorder characterized by onset of seizures usually in the first year of life and associated with intellectual disability, poor motor development, and poor or absent speech. Additional features include hypotonia, abnormal movements, and nonspecific dysmorphic features. The severity is variable: some patients are unable to speak, walk, or interact with others as late as the teenage years, whereas others may have some comprehension (summary by Straub et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome
MedGen UID:
1648389
Concept ID:
C4746975
Disease or Syndrome
DFNX7 is a congenital form of bilateral mixed or conductive hearing loss, which may be progressive. It is not associated with vestibular symptoms (Xing et al., 2017).
Coffin-Siris syndrome 7
MedGen UID:
1648281
Concept ID:
C4747954
Disease or Syndrome
Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment.
Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome
MedGen UID:
1656239
Concept ID:
C4750837
Disease or Syndrome
ASXL3-related disorder is characterized by developmental delay or intellectual disability, typically in the moderate to severe range, with speech and language delay and/or absent speech. Affected individuals may also display autistic features. There may be issues with feeding. While dysmorphic facial features have been described, they are typically nonspecific. Affected individuals may also have hypotonia that can transition to spasticity resulting in unusual posture with flexion contractions of the elbows, wrists, and fingers. Other findings may include poor postnatal growth, strabismus, seizures, sleep disturbance, and dental anomalies.
Menke-Hennekam syndrome 1
MedGen UID:
1675629
Concept ID:
C5193034
Disease or Syndrome
Menke-Hennekam syndrome-1 (MKHK1) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, hearing impairment, short stature, and microcephaly are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-1 (RSTS1; 180849), patients with MKHK1 do not resemble the striking phenotype of RSTS1. Genetic Heterogeneity of Menke-Hennekam Syndrome Menke-Hennekam syndrome-2 (MKHK2; 618333) is caused by heterozygous mutation in exons 30 or 31 of the EP300 gene (602700). Mutation elsewhere in that gene results in RSTS2 (613684).
Coffin-Siris syndrome 8
MedGen UID:
1679527
Concept ID:
C5193054
Disease or Syndrome
Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment.
Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
MedGen UID:
1684142
Concept ID:
C5193057
Disease or Syndrome
A rare, genetic, neurometabolic disease characterized by microcephaly, short stature, epilepsy, cerebral hypomyelination, severe global developmental delay, and progressive spasticity. Macrocytic anemia and hyperthermia have also been reported in association. Brain imaging reveals delayed myelination with minimal progression over time, mild cerebellar atrophy and/or thin corpus callosum.
Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome
MedGen UID:
1679105
Concept ID:
C5193066
Disease or Syndrome
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by variable intellectual disability and/or developmental delay, epilepsy, generalized hypertrichosis, severe gingival overgrowth and visual impairment in some patients. Common craniofacial features include bitemporal narrowing, bushy and straight eyebrows, long eyelashes, low-set ears, deep/short philtrum, everted upper lip, prominent upper and lower vermilion, wide mouth, micrognathia, and retrognathia.
Neurodevelopmental disorder with or without variable brain abnormalities; NEDBA
MedGen UID:
1675664
Concept ID:
C5193102
Disease or Syndrome
Neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) is characterized by global developmental delay apparent from infancy or early childhood, resulting in mildly delayed walking, variably impaired intellectual development, and poor or absent speech. Additional features may include hypotonia, spasticity, or ataxia. About half of patients have abnormal findings on brain imaging, including cerebral or cerebellar atrophy, loss of white matter volume, thin corpus callosum, and perisylvian polymicrogyria. Seizures are not a prominent finding, and although some patients may have nonspecific dysmorphic facial features, there is no common or consistent gestalt (summary by Platzer et al., 2019).
Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies
MedGen UID:
1684881
Concept ID:
C5231426
Disease or Syndrome
Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies (IDNADFS) is characterized by mildly impaired global development, speech delay with nasal speech, and dysmorphic facial features, including high forehead, midface hypoplasia, micrognathia or high-arched palate, hypo/hypertelorism, upslanting palpebral fissures, and thin upper lip. Some patients may have skeletal anomalies, such as brachydactyly, 2-3 toe syndactyly, and flat feet (summary by Alesi et al., 2019 and Uehara et al., 2019).
Zimmermann-laband syndrome 3
MedGen UID:
1684740
Concept ID:
C5231447
Disease or Syndrome
Zimmermann-Laband syndrome-3 (ZLS3) is characterized by developmental delay, intellectual disability, coarse face, gingival hyperplasia, and nail hypoplasia/aplasia (Bauer et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of Zimmermann-Laband syndrome, see ZLS1 (135500).
Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures
MedGen UID:
1684879
Concept ID:
C5231486
Disease or Syndrome
Complex cortical dysplasia with other brain malformations-15 (CDCBM15) is an autosomal recessive neurologic disorder characterized by progressive microcephaly associated with abnormal facial features, hypotonia, and variable global developmental delay with impaired intellectual development. Brain imaging shows variable malformation of cortical development on the lissencephaly spectrum, mainly pachygyria and thin corpus callosum (summary by Mitani et al., 2019). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).
CEBALID syndrome
MedGen UID:
1710973
Concept ID:
C5394044
Disease or Syndrome
Individuals with MN1 C-terminal truncation (MCTT) syndrome have mild-to-moderate intellectual disability, severe expressive language delay, dysmorphic facial features (midface hypoplasia, downslanting palpebral fissures, hypertelorism, exophthalmia, short upturned nose, and small low-set ears), and distinctive findings on brain imaging (including perisylvian polymicrogyria and atypical rhombencephalosynapsis). Mild-to-moderate prelingual hearing loss (usually bilateral, conductive, and/or sensorineural) is common. Generalized seizures (observed in the minority of individuals) are responsive to anti-seizure medication. There is an increased risk for craniosynostosis and, thus, increased intracranial pressure. To date, 25 individuals with MCTT syndrome have been identified.
Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation
MedGen UID:
1716098
Concept ID:
C5394091
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (NEDHRIT) is a severe autosomal recessive disorder characterized by neonatal respiratory distress, poor feeding, and impaired global development. Affected individuals are unable to walk or speak and have poor or absent eye contact. Some patients may develop seizures (summary by Wagner et al., 2020).
Suleiman-El-Hattab syndrome
MedGen UID:
1738652
Concept ID:
C5436458
Disease or Syndrome
Suleiman-El-Hattab syndrome (SULEHS) is an autosomal recessive multisystem developmental disorder characterized by hypotonia and feeding difficulties soon after birth, global developmental delay with impaired intellectual development and poor expressive speech, and a general happy demeanor. There is a distinctive facial appearance with microcephaly, thick arched eyebrows with synophrys, hypertelorism, epicanthal folds, low-set ears, broad nasal bridge, and thin upper lip. Additional more variable features include recurrent respiratory infections, cardiovascular malformations, cryptorchidism, seizures, and distal anomalies of the hands and feet (summary by Suleiman et al., 2019).
Tolchin-Le Caignec syndrome
MedGen UID:
1724999
Concept ID:
C5436509
Disease or Syndrome
Tolchin-Le Caignec syndrome (TOLCAS) is a developmental disorder characterized by mildly to moderately impaired intellectual development and behavioral problems, such as autism, ADHD, labile mood, and aggressive episodes. Many patients have bony abnormalities, including osteochondroma, craniosynostosis, dysmorphic facies, arachnodactyly, and large head circumference. Rarely, additional congenital anomalies may also be observed. These additional features and the bony defects are highly variable (summary by Tolchin et al., 2020).
Intellectual developmental disorder with seizures and language delay
MedGen UID:
1740295
Concept ID:
C5436574
Disease or Syndrome
SETD1B-related neurodevelopmental disorder (SETD1B-NDD) is characterized by developmental delay (mainly affecting speech and language), intellectual disability, seizures, autism spectrum disorder or autism-like behaviors, and additional behavioral concerns. Speech delay and/or language disorder has been reported in most affected individuals. Delay in gross motor skills and mild-to-moderate intellectual disability are common. Most affected individuals have seizures with variable onset and seizure type. Behavioral issues including hyperactivity, aggression, anxiety, and sleep disorders have been reported in approximately half of individuals. Less common features include ophthalmologic manifestations and feeding issues.
Blepharophimosis-impaired intellectual development syndrome
MedGen UID:
1779966
Concept ID:
C5443984
Disease or Syndrome
Blepharophimosis-impaired intellectual development syndrome (BIS) is a congenital disorder characterized by a distinct facial appearance with blepharophimosis and global development delay. Affected individuals have delayed motor skills, sometimes with inability to walk, and impaired intellectual development with poor or absent speech; some patients show behavioral abnormalities. There are recognizable facial features, including epicanthal folds, sparse eyebrows, broad nasal bridge, short nose with downturned tip, and open mouth with thin upper lip. Other more variable features include distal skeletal anomalies, feeding difficulties with poor growth, respiratory infections, and hypotonia with peripheral spasticity (summary by Cappuccio et al., 2020).
Coffin-Siris syndrome 12
MedGen UID:
1782096
Concept ID:
C5444111
Disease or Syndrome
Coffin-Siris syndrome-12 (CSS12) is a neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, speech and language delay, and behavioral abnormalities, such as autism or hyperactivity. Affected individuals may have hypotonia and poor feeding in infancy. There are variable dysmorphic facial features, although most patients do not have the classic hypoplastic fifth digit/nail abnormalities that are often observed in other forms of CSS (Barish et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Li-Campeau syndrome
MedGen UID:
1788485
Concept ID:
C5543068
Disease or Syndrome
Li-Campeau syndrome (LICAS) is an autosomal recessive syndromic neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development, dysmorphic facial features, hypothyroidism, and variable abnormalities of the cardiac and genital systems. Additional features may include seizures, short stature, hypotonia, and brain imaging anomalies, such as cortical atrophy (summary by Li et al., 2021).
Kohlschutter-Tonz syndrome-like
MedGen UID:
1781649
Concept ID:
C5543202
Disease or Syndrome
Den Hoed-de Boer-Voisin syndrome (DHDBV) is characterized by global developmental delay with moderately to severely impaired intellectual development, poor or absent speech, and delayed motor skills. Although the severity of the disorder varies, many patients are nonverbal and have hypotonia with inability to sit or walk. Early-onset epilepsy is common and may be refractory to treatment, leading to epileptic encephalopathy and further interruption of developmental progress. Most patients have feeding difficulties with poor overall growth and dysmorphic facial features, as well as significant dental anomalies resembling amelogenesis imperfecta. The phenotype is reminiscent of Kohlschutter-Tonz syndrome (KTZS; 226750). More variable features of DHDBV include visual defects, behavioral abnormalities, and nonspecific involvement of other organ systems (summary by den Hoed et al., 2021).
Radio-Tartaglia syndrome
MedGen UID:
1778557
Concept ID:
C5543339
Disease or Syndrome
Radio-Tartaglia syndrome (RATARS) is a neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show hypotonia, mild motor difficulties, and craniofacial dysmorphism. Brain imaging may show nonspecific defects; rare patients have seizures or pyramidal signs. A subset of individuals may have congenital heart defects, precocious puberty, and obesity in females. Some of the features are similar to those observed in patients with chromosome 1p36 deletion syndrome (607872) (summary by Radio et al., 2021).
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities
MedGen UID:
1780615
Concept ID:
C5543591
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (NEDHFBA) is an autosomal recessive neurologic syndrome characterized by global developmental delay with severely impaired intellectual development, hypotonia and muscle weakness, often resulting in the inability to walk or sit, and characteristic coarse facial features. Additional features include feeding difficulties, respiratory distress, scoliosis, poor visual function, and rotary nystagmus. Brain imaging shows variable abnormalities, including enlarged ventricles, decreased white matter volume, white matter changes, thin corpus callosum, and cerebellar hypoplasia (summary by Loddo et al., 2020).
White-Kernohan syndrome
MedGen UID:
1785087
Concept ID:
C5543635
Disease or Syndrome
White-Kernohan syndrome (WHIKERS) is a neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, hypotonia, and characteristic facial features. Some patients may have abnormalities of other systems, including genitourinary and skeletal (summary by White et al., 2021).
Neuroocular syndrome
MedGen UID:
1790414
Concept ID:
C5551362
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities
MedGen UID:
1794167
Concept ID:
C5561957
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).
Neurodevelopmental disorder with hypotonia and dysmorphic facies
MedGen UID:
1794184
Concept ID:
C5561974
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF) is characterized by global developmental delay and hypotonia apparent from birth. Affected individuals have variably impaired intellectual development, often with speech delay and delayed walking. Seizures are generally not observed, although some patients may have single seizures or late-onset epilepsy. Most patients have prominent dysmorphic facial features. Additional features may include congenital cardiac defects (without arrhythmia), nonspecific renal anomalies, joint contractures or joint hyperextensibility, dry skin, and cryptorchidism. There is significant phenotypic variability in both the neurologic and extraneurologic manifestations (summary by Tan et al., 2022).
Neurodevelopmental disorder with hypotonia and brain abnormalities
MedGen UID:
1794187
Concept ID:
C5561977
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and brain abnormalities (NEDHYBA) is characterized by impaired development of motor skills, cognitive function, and speech acquisition beginning in infancy or early childhood. Some affected individuals may have feeding difficulties, seizures, behavioral abnormalities, and nonspecific dysmorphic facial features. Brain imaging shows variable abnormalities, including corpus callosum defects, cerebellar defects, and decreased white matter volume. There is significant phenotypic variability (summary by Duncan et al., 2021).
Acromesomelic dysplasia 4
MedGen UID:
1794238
Concept ID:
C5562028
Disease or Syndrome
Acromesomelic dysplasia-4 (AMD4) is characterized by disproportionate short stature due to mesomelic shortening of the limbs. Radiographic hallmarks include mild to moderate platyspondyly, moderate brachydactyly, iliac flaring, and metaphyseal alterations of the long bones that progressively increase with age (Diaz-Gonzalez et al., 2022). For a discussion of genetic heterogeneity of acromesomelic dysplasia, see AMD1 (602875).
Hengel-Maroofian-Schols syndrome
MedGen UID:
1794242
Concept ID:
C5562032
Disease or Syndrome
Hengel-Maroofian-Schols syndrome (HEMARS) is an autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay apparent from infancy or early childhood. Affected individuals have delayed walking or inability to walk, impaired intellectual development with poor or absent speech, pyramidal signs manifest as lower limb spasticity, poor overall growth often with short stature and microcephaly, and dysmorphic facial features. Some patients develop seizures. Brain imaging shows thinning of the posterior part of the corpus callosum, delayed myelination, and cerebral and cerebellar atrophy (Hengel et al., 2021).
Schaaf-Yang syndrome
MedGen UID:
1807366
Concept ID:
C5575066
Disease or Syndrome
Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder that shares multiple clinical features with the genetically related Prader-Willi syndrome. It usually manifests at birth with muscular hypotonia in all and distal joint contractures in a majority of affected individuals. Gastrointestinal/feeding problems are particularly pronounced in infancy and childhood, but can transition to hyperphagia and obesity in adulthood. Respiratory distress is present in many individuals at birth, with approximately half requiring intubation and mechanical ventilation, and approximately 20% requiring tracheostomy. Skeletal manifestations such as joint contractures, scoliosis, and decreased bone mineral density are frequently observed. All affected individuals show developmental delay, resulting in intellectual disability of variable degree, from low-normal intelligence to severe intellectual disability. Other findings may include short stature, seizures, eye anomalies, and hypogonadism.
Teebi hypertelorism syndrome 2
MedGen UID:
1809276
Concept ID:
C5676911
Disease or Syndrome
Teebi hypertelorism syndrome-2 (TBHS2) is characterized primarily by hypertelorism, prominent forehead, thick and broad eyebrows, and short nose with depressed nasal root and broad nasal tip. Other features include thin upper lip, small chin with horizontal crease, and high or cleft palate. Developmental delay and/or impaired intellectual development have been observed in some patients (Li et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of Teebi hypertelorism syndrome, see TBHS1 (145420).
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities
MedGen UID:
1803456
Concept ID:
C5676965
Disease or Syndrome
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities (NEDNMS) is an autosomal recessive disorder characterized by global developmental delay apparent from infancy or early childhood. The severity of the disorder is highly variable. Affected individuals show impaired intellectual development and motor delay associated with either severe hypotonia or hypertonia and spasticity. Most affected individuals have skeletal defects and dysmorphic facial features. Some may have ocular or auditory problems, peripheral neuropathy, behavioral abnormalities, and nonspecific findings on brain imaging (Kurolap et al., 2022).
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1
MedGen UID:
1808104
Concept ID:
C5677021
Disease or Syndrome
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1) is characterized by cranial involvement with macrocrania at birth, brachycephaly, anomalies of middle fossa structures including hypoplasia of corpus callosum, enlargement of septum pellucidum, and dilated lateral ventricles, as well as cortical atrophy and hypodensity of the gray matter. Facial dysmorphisms include flat face, hypertelorism, epicanthal folds, synophrys, broad nasal bridge, cleft lip and cleft palate, and low-set posteriorly rotated ears. Patients also exhibit short neck and multiple costal and vertebral anomalies. The face is rather characteristic, and various authors have consistently reported affable/friendly personality, despite intellectual delay (summary by Alanay et al., 2014). Genetic Heterogeneity of Craniofacial Dysmorphism, Skeletal Anomalies, and Impaired Intellectual Development Syndrome CFSMR2 (616994) is caused by mutation in the RAB5IF gene (619960) on chromosome 20q11.
DeSanto-Shinawi syndrome due to WAC point mutation
MedGen UID:
1841517
Concept ID:
C5681129
Disease or Syndrome
WAC-related intellectual disability (ID) is typically characterized by variable degrees of developmental delay and/or intellectual disability. Behavioral abnormalities including anxiety, attention-deficit/hyperactivity disorder, and/or autism spectrum disorder are observed in the majority of older children and adults. Most affected infants have significant but nonspecific features at birth such as neonatal hypotonia and feeding problems. Some affected individuals come to medical attention with respiratory or vision problems. Facial features may be mildly dysmorphic, but are nonspecific. To date, 18 individuals have been identified with WAC-related ID.
Microcephaly 29, primary, autosomal recessive
MedGen UID:
1823993
Concept ID:
C5774220
Disease or Syndrome
Autosomal recessive primary microcephaly-29 (MCPH29) is characterized by small head circumference apparent at birth and associated with global developmental delay, impaired intellectual development, speech delay, and behavioral abnormalities. Affected individuals also have poor overall growth with short stature, mild dysmorphic facial features, and seizures (Khan et al., 2020). For a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss
MedGen UID:
1824002
Concept ID:
C5774229
Disease or Syndrome
Birk-Aharoni syndrome (BKAH) is a severe neurodevelopmental disorder characterized developmental delay, impaired intellectual development, absent speech, spastic tetraplegia with central hypotonia, chorea, inability to walk, hearing loss, micropenis, undescended testes, and mildly elevated liver enzymes (Aharoni et al., 2022).
Developmental delay with variable intellectual disability and dysmorphic facies
MedGen UID:
1824015
Concept ID:
C5774242
Disease or Syndrome
Developmental delay with variable intellectual disability and dysmorphic facies (DIDDF) is a clinically heterogeneous disorder characterized by neurologic deficits and characteristic dysmorphic facial features apparent from infancy or early childhood. Affected individuals usually show impaired intellectual development, speech delay, learning difficulties, and/or behavioral problems. Additional features may include hypotonia, hand or foot deformities, and palatal defects (Verberne et al., 2021; Verberne et al., 2022).
Tessadori-Van Haaften neurodevelopmental syndrome 3
MedGen UID:
1824083
Concept ID:
C5774310
Disease or Syndrome
Tessadori-Bicknell-van Haaften neurodevelopmental syndrome-3 (TEBIVANED3) is characterized by global developmental delay with poor overall growth, impaired intellectual development, and speech difficulties. More variable features include hypotonia, microcephaly, and dysmorphic facies. The severity and manifestations of the disorder are highly variable (Tessadori et al., 2022). For a discussion of genetic heterogeneity of Tessadori-Bicknell-van Haaften neurodevelopmental disorder, see TEBIVANED1 (619758).
Intellectual developmental disorder, autosomal dominant 73
MedGen UID:
1841272
Concept ID:
C5830636
Mental or Behavioral Dysfunction
Autosomal dominant intellectual developmental disorder-73 (MRD73) is a highly variable neurodevelopmental disorder characterized by impaired intellectual development that ranges from mild to severe, speech delay, behavioral abnormalities, and nonspecific dysmorphic facial features (Janssen et al., 2022).

Professional guidelines

PubMed

Gerkowicz A, Bartosińska J, Raczkiewicz D, Kwaśny M, Krasowska D
Sensors (Basel) 2021 Sep 6;21(17) doi: 10.3390/s21175981. PMID: 34502871Free PMC Article
Chanasumon N, Sriphojanart T, Suchonwanit P
Drug Des Devel Ther 2018;12:365-372. Epub 2018 Feb 22 doi: 10.2147/DDDT.S156467. PMID: 29503529Free PMC Article
Maas SM, Shaw AC, Bikker H, Lüdecke HJ, van der Tuin K, Badura-Stronka M, Belligni E, Biamino E, Bonati MT, Carvalho DR, Cobben J, de Man SA, Den Hollander NS, Di Donato N, Garavelli L, Grønborg S, Herkert JC, Hoogeboom AJ, Jamsheer A, Latos-Bielenska A, Maat-Kievit A, Magnani C, Marcelis C, Mathijssen IB, Nielsen M, Otten E, Ousager LB, Pilch J, Plomp A, Poke G, Poluha A, Posmyk R, Rieubland C, Silengo M, Simon M, Steichen E, Stumpel C, Szakszon K, Polonkai E, van den Ende J, van der Steen A, van Essen T, van Haeringen A, van Hagen JM, Verheij JB, Mannens MM, Hennekam RC
Eur J Med Genet 2015 May;58(5):279-92. Epub 2015 Mar 16 doi: 10.1016/j.ejmg.2015.03.002. PMID: 25792522

Recent clinical studies

Diagnosis

De Falco A, De Brasi D, Della Monica M, Cesario C, Petrocchi S, Novelli A, D'Alterio G, Iolascon A, Capasso M, Piscopo C
Genes (Basel) 2023 Jan 1;14(1) doi: 10.3390/genes14010119. PMID: 36672860Free PMC Article
Koboldt DC, Mihalic Mosher T, Kelly BJ, Sites E, Bartholomew D, Hickey SE, McBride K, Wilson RK, White P
Cold Spring Harb Mol Case Stud 2018 Jun;4(3) Epub 2018 Jun 1 doi: 10.1101/mcs.a002410. PMID: 29305346Free PMC Article

Prognosis

Zepeda-Mendoza CJ, Cousin MA, Basu S, Jenkinson G, Oliver G, Pittock ST, Baughn LB, Klee EW, Babovic-Vuksanovic D
Cold Spring Harb Mol Case Stud 2019 Dec;5(6) Epub 2019 Dec 13 doi: 10.1101/mcs.a004655. PMID: 31662300Free PMC Article
Koboldt DC, Kastury RD, Waldrop MA, Kelly BJ, Mosher TM, McLaughlin H, Corsmeier D, Slaughter JL, Flanigan KM, McBride KL, Mehta L, Wilson RK, White P
Cold Spring Harb Mol Case Stud 2018 Oct;4(5) Epub 2018 Oct 1 doi: 10.1101/mcs.a003160. PMID: 30054298Free PMC Article

Clinical prediction guides

Zepeda-Mendoza CJ, Cousin MA, Basu S, Jenkinson G, Oliver G, Pittock ST, Baughn LB, Klee EW, Babovic-Vuksanovic D
Cold Spring Harb Mol Case Stud 2019 Dec;5(6) Epub 2019 Dec 13 doi: 10.1101/mcs.a004655. PMID: 31662300Free PMC Article
Koboldt DC, Kastury RD, Waldrop MA, Kelly BJ, Mosher TM, McLaughlin H, Corsmeier D, Slaughter JL, Flanigan KM, McBride KL, Mehta L, Wilson RK, White P
Cold Spring Harb Mol Case Stud 2018 Oct;4(5) Epub 2018 Oct 1 doi: 10.1101/mcs.a003160. PMID: 30054298Free PMC Article
Koboldt DC, Mihalic Mosher T, Kelly BJ, Sites E, Bartholomew D, Hickey SE, McBride K, Wilson RK, White P
Cold Spring Harb Mol Case Stud 2018 Jun;4(3) Epub 2018 Jun 1 doi: 10.1101/mcs.a002410. PMID: 29305346Free PMC Article

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