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Thin upper lip vermilion

MedGen UID:
355352
Concept ID:
C1865017
Finding
Synonyms: Decreased height of upper lip vermilion; Decreased volume of upper lip; Decreased volume of upper lip vermilion; Thin red part of the upper lip; Thin upper lip; Thin upper lips; Thin vermilion border of upper lip
 
HPO: HP:0000219

Definition

Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVThin upper lip vermilion

Conditions with this feature

Glycogen storage disease type III
MedGen UID:
6641
Concept ID:
C0017922
Disease or Syndrome
An autosomal recessive inherited type of glycogen storage disease caused by deficiency of the glycogen debranching enzyme. It results in the accumulation of structurally abnormal glycogen in the heart, skeletal muscles, and/or liver.
Prader-Willi syndrome
MedGen UID:
46057
Concept ID:
C0032897
Disease or Syndrome
A genetic syndrome caused by deletions or disruptions of chromosome 15. It is characterized by reduced fetal activity, mental retardation, hypotonia, short stature, and hypogonadism.
Miller Dieker syndrome
MedGen UID:
78538
Concept ID:
C0265219
Disease or Syndrome
A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.
Femoral hypoplasia - unusual facies syndrome
MedGen UID:
120523
Concept ID:
C0265263
Disease or Syndrome
Femoral-facial syndrome (FFS), also known as femoral hypoplasia-unusual facies syndrome (FHUFS), is a rare and sporadic multiple congenital anomaly syndrome comprising bilateral femoral hypoplasia and characteristic facial features, such as long philtrum, thin upper lip, micrognathia with or without cleft palate, upward-slanting palpebral fissures, and a short nose with broad tip. Other features, such as renal anomalies, are more variable (summary by Nowaczyk et al., 2010).
Pallister-Killian syndrome
MedGen UID:
120540
Concept ID:
C0265449
Disease or Syndrome
A very rare chromosomal disorder caused by tetrasomy of chromosome 12p. It is characterized by severe mental retardation, prominent forehead, sparse temporofrontal hair, hypertelorism, short nose, and streaks of hypopigmented skin.
Adenylosuccinate lyase deficiency
MedGen UID:
78641
Concept ID:
C0268126
Disease or Syndrome
A disorder of purine metabolism characterized by intellectual disability, psychomotor delay and/or regression, seizures, and autistic features.
Histidine transport defect
MedGen UID:
82825
Concept ID:
C0268642
Disease or Syndrome
An increased concentration of histidine in the urine.
Symphalangism-brachydactyly syndrome
MedGen UID:
90977
Concept ID:
C0342282
Disease or Syndrome
Multiple synostoses syndrome is characterized by multiple joint fusions, usually commencing in the hands, conductive deafness, and characteristic facial features, including a broad, tubular-shaped nose and a thin upper vermilion. Other features include brachydactyly, hypoplastic or absent middle phalanges, radial head dislocation, and pectus carinatum (summary by Takahashi et al., 2001). Genetic Heterogeneity of Multiple Synostoses Syndrome Other forms of multiple synostoses syndrome include SYNS2 (610017), caused by mutation in the GDF5 gene (601146) on chromosome 20q11; SYNS3 (612961), caused by mutation in the FGF9 gene (600921) on chromosome 13q12; and SYNS4 (617898), caused by mutation in the GDF6 gene (601147) on chromosome 8q22.
Sialuria
MedGen UID:
137980
Concept ID:
C0342853
Disease or Syndrome
A rare, autosomal recessive lysosomal storage disease caused by mutations in the SLC17A5 gene. It primarily affects the nervous system. Signs and symptoms include developmental delay, intellectual disability, hypotonia, failure to thrive, seizures, and ataxia.
Congenital disorder of glycosylation, type Ia
MedGen UID:
138111
Concept ID:
C0349653
Disease or Syndrome
A congenital disorder of glycosylation sub-type caused by mutation(s) in the PMM2 gene, encoding phosphomannomutase 2.
Trichorhinophalangeal dysplasia type I
MedGen UID:
140929
Concept ID:
C0432233
Disease or Syndrome
A rare autosomal dominant syndrome caused by mutations in the TRPS1 gene. It is characterized by distinctive facial appearance (sparse hair, pear-shaped nose, and elongated philtrum), skeletal abnormalities (cone-shaped epiphyses, hip malformation), short stature, and mild growth retardation.
Deletion of long arm of chromosome 18
MedGen UID:
96605
Concept ID:
C0432443
Disease or Syndrome
A condition in which some or all of the cells of the body contain extra genetic material from chromosome 18. Clinical features of this condition may include the following: spina bifida, hearing loss, cleft lip, cleft palate, undescended testes, rocker bottom feet, micrognathia, low set ears, cardiac anomalies (ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot), intellectual disability, holoprosencephaly, pituitary dysplasia, seizures, autoimmune disorders, hip dysplasia, and/or congenital cataracts.
Recombinant 8 syndrome
MedGen UID:
167070
Concept ID:
C0795822
Disease or Syndrome
Recombinant 8 (rec(8)) syndrome, also known as San Luis Valley syndrome, is a complex chromosomal disorder that is due to a parental pericentric inversion of chromosome 8 and is characterized by major congenital heart anomalies, urogenital malformations, moderate to severe intellectual deficiency and mild craniofacial dysmorphism.
Chromosome 9p deletion syndrome
MedGen UID:
167073
Concept ID:
C0795830
Disease or Syndrome
A rare chromosomal anomaly with characteristics of psychomotor developmental delay, facial dysmorphism (trigonocephaly, midface hypoplasia, upslanting palpebral fissures, dysplastic small ears, flat nasal bridge with anteverted nostrils and long philtrum, micrognathia, choanal atresia, short neck), single umbilical artery, omphalocele, inguinal or umbilical hernia, genital abnormalities (hypospadia, cryptorchidism), muscular hypotonia and scoliosis.
DOORS syndrome
MedGen UID:
208648
Concept ID:
C0795934
Disease or Syndrome
A multiple congenital anomalies, intellectual disability syndrome with characteristics of sensorineural hearing loss, onychodystrophy, osteodystrophy, mild to profound intellectual disability and seizures. About 50 cases have been reported to date. Caused by mutations in the TBC1D24 gene (16p13.3) encoding a protein involved in the regulation of membrane trafficking. Inherited autosomal recessively.
Fine-Lubinsky syndrome
MedGen UID:
163198
Concept ID:
C0795941
Disease or Syndrome
A rare multiple congenital anomalies/dysmorphic syndrome characterized by psychomotor delay, brachycephaly with flat face, small nose, microstomia, cleft palate, cataract, hearing loss, hypoplastic scrotum, and digital anomalies.
Peters plus syndrome
MedGen UID:
163204
Concept ID:
C0796012
Disease or Syndrome
A rare, autosomal recessive inherited syndrome caused by mutations in the B3GALTL gene. It is characterized by abnormalities in the anterior chamber of the eye, short stature, cleft lip with or without cleft palate, distinctive facial features, and intellectual disability.
X-linked mental retardation with marfanoid habitus syndrome
MedGen UID:
167096
Concept ID:
C0796022
Disease or Syndrome
The Lujan-Fryns syndrome or X-linked mental retardation (XLMR) with marfanoid habitus syndrome is a syndromic X-linked form of intellectual disability, associated with tall, marfanoid stature, distinct facial dysmorphism and behavioral problems.
Intellectual disability, Buenos-Aires type
MedGen UID:
167102
Concept ID:
C0796080
Disease or Syndrome
A rare intellectual disability syndrome with characteristics of growth retardation, microcephaly, characteristic facial features (including narrow forehead, bushy eyebrows, hypertelorism, small, downward-slanting palpebral fissures with blepharoptosis, malformed and low-set ears, broad straight nose, thin upper lip and a wide, tented mouth), developmental delay, intellectual disability, speech disorder, and multiple organ malformations (e.g. ventricular septal defect, megaloureter, dilated renal pelvis). Additional manifestations reported include neurocutaneous lesions (including palmoplantar hyperkeratosis), internal hydrocephalus, and bilateral partial soft-tissue syndactyly of second and third toe.
Myhre syndrome
MedGen UID:
167103
Concept ID:
C0796081
Disease or Syndrome
A rare, autosomal dominant inherited disorder caused by mutations in the SMAD4 gene. It is characterized by developmental abnormalities, mild to moderate intellectual disability, hearing loss, skin stiffness, skeletal abnormalities, and typical facial features (short palpebral fissures, shortened distance between the nose and upper lip, midface hypoplasia, prognathism, cleft palate, and/or cleft lip).
Renpenning syndrome 1
MedGen UID:
208670
Concept ID:
C0796135
Disease or Syndrome
An X-linked recessive disorder caused by mutation(s) in the PQBP1 gene, encoding polyglutamine-binding protein 1. It is characterized by moderate to severe intellectual disability, developmental delay and characteristic dysmorphic features, which may include short stature, microcephaly, and a narrow face.
Mental retardation 30, X-linked
MedGen UID:
163235
Concept ID:
C0796237
Disease or Syndrome
Nonsyndromic mental retardation with microcephaly, restlessness, and hyperactivity.
X-linked intellectual disability Brooks type
MedGen UID:
208682
Concept ID:
C0796272
Disease or Syndrome
A rare X-linked intellectual disability syndrome with characteristics of failure to thrive, speech delay, intellectual disability, muscle hypotonia, spastic diplegia, optic atrophy with myopia and distinct facial features (including triangular face, bifrontal narrowness, deeply set eyes, low-set/cupped ears, prominent nose, short philtrum, and thin upper lip with tented morphology) that can be evident from birth. Additional manifestations reported in some patients include large joint contractures and pectus excavatum (which become more evident with age) and seizures.
Elsahy-Waters syndrome
MedGen UID:
923028
Concept ID:
C0809936
Disease or Syndrome
An extremely rare multiple congenital anomalies/dysmorphic syndrome, described in three boys from one family. The syndrome has characteristics of intellectual disability, hypertelorism, broad and flat nasal bridge, maxillary hypoplasia, mandibular prognathism, bifid uvula or partial cleft palate, multiple dental cysts, Schmorl nodes, fused cervical spinous processes, pectus excavatum, and penoscrotal hypospadias. There have been no further descriptions in the literature since 1971.
Andersen Tawil syndrome
MedGen UID:
327586
Concept ID:
C1563715
Disease or Syndrome
A form of inherited long QT syndrome (or LQT7) that is characterized by a triad of potassium-sensitive periodic paralysis, VENTRICULAR ECTOPIC BEATS, and abnormal features such as short stature, low-set ears, and SCOLIOSIS. It results from mutations of KCNJ2 gene which encodes a channel protein (INWARD RECTIFIER POTASSIUM CHANNELS) that regulates resting membrane potential.
Opitz GBBB syndrome, type II
MedGen UID:
321463
Concept ID:
C1801950
Disease or Syndrome
An X-linked syndrome caused by mutations in the MID1 gene or autosomal dominant syndrome caused by changes in chromosome 22. It is characterized by ocular hypertelorism, and defects of the larynx, trachea, or esophagus. Most males have hypospadias, cryptorchidism, underdeveloped scrotum, or a scrotum divided into two lobes. Mild intellectual disability and developmental delays occur in approximately half of the affected individuals.
Congenital muscular hypertrophy-cerebral syndrome
MedGen UID:
315658
Concept ID:
C1802395
Disease or Syndrome
An X-linked inherited form of Cornelia De Lange syndrome caused by mutations in the SMC1A gene mapped to chromosome Xp11.22. Patients have a milder form of the syndrome compared to patients with the NIPBL gene mutation.
Ayme-gripp syndrome
MedGen UID:
371416
Concept ID:
C1832812
Disease or Syndrome
Aymé-Gripp syndrome is classically defined as the triad of bilateral early cataracts, sensorineural hearing loss, and characteristic facial features in combination with neurodevelopmental abnormalities. The facial features are often described as "Down syndrome-like" and include brachycephaly, flat facial appearance, short nose, long philtrum, narrow mouth, and low-set and posteriorly rotated ears. Hearing loss is often congenital. Other features may include postnatal short stature, seizure disorder, nonspecific brain abnormalities on head imaging, skeletal abnormalities, and joint limitations. A subset of individuals have been found to have pericarditis or pericardial effusion during the neonatal or infantile period. All affected individuals have had developmental delay, but the degree of cognitive impairment is extremely variable. Other features including gastrointestinal and endocrine abnormalities, ectodermal dysplasia (i.e., nail dystrophy and mammary gland hypoplasia), dental anomalies, and chronic glomerulopathy with proteinuria have been reported in rare affected individuals.
Timothy syndrome
MedGen UID:
331395
Concept ID:
C1832916
Disease or Syndrome
A multi-system disorder characterized by cardiac, hand, facial and neurodevelopmental features that include QT prolongation, webbed fingers and toes, flattened nasal bridge, low-set ears, small upper jaw, thin upper lip, and characteristic features of autism or autistic spectrum disorders.
Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation
MedGen UID:
320559
Concept ID:
C1835265
Disease or Syndrome
Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is a rare autosomal dominant condition characterized by variable expression of microcephaly, ocular disorders including chorioretinopathy, congenital lymphedema of the lower limbs, and mild to moderate intellectual disability.
Mental retardation with optic atrophy, facial dysmorphism, microcephaly, and short stature
MedGen UID:
324635
Concept ID:
C1836915
Disease or Syndrome
AICAR transformylase/IMP cyclohydrolase deficiency
MedGen UID:
332474
Concept ID:
C1837530
Disease or Syndrome
AICA-ribosuria is characterized by severe to profound global neurodevelopmental impairment, severe visual impairment due to chorioretinal atrophy, ante-postnatal growth impairment, and severe scoliosis. Dysmorphic features include coarse facies and upturned nose. Early-onset epilepsy may occur. Less common features may include aortic coarctation, chronic hepatic cytolysis, minor genital malformations, and nephrocalcinosis (Ramond et al., 2020).
Fryns macrocephaly
MedGen UID:
373933
Concept ID:
C1838281
Disease or Syndrome
A rare syndrome with features of multiple congenital anomalies with macrocephaly (of post-natal onset), large anterior fontanelle, progressive complex spastic paraplegia, coarse facial features (broad and high forehead, deeply set eyes, short philtrum with thin upper lip, large mouth and prominent incisors), seizures, and intellectual deficit of varying severity. Inheritance appears to be autosomal recessive.
Hermansky-Pudlak syndrome 2
MedGen UID:
374912
Concept ID:
C1842362
Disease or Syndrome
An autosomal recessive sub-type of Hermansky-Pudlak syndrome caused by mutation(s) in the AP3B1, encoding AP-3 complex subunit beta-1. Immunodeficiency due to neutropenia is a characteristic of this sub-type.
8q22.1 microdeletion syndrome
MedGen UID:
334165
Concept ID:
C1842464
Disease or Syndrome
A rare microdeletion syndrome associated with a distinct facial appearance. It has been reported in four unrelated patients. A mask-like facial appearance is the most characteristic feature with blepharophimosis, tight appearing glistening facial skin, flat and broad nose, dysplastic ears and unusual scalp hair pattern. Camptodactyly, joint contractures, unusual dentition and mild developmental delay can be observed. Cryptorchidism in boys and a happy disposition are constant.
Craniolenticulosutural dysplasia
MedGen UID:
334671
Concept ID:
C1843042
Disease or Syndrome
Craniolenticulosutural dysplasia (CLSD), also known as Boyadjiev-Jabs syndrome, is characterized by the specific association of large and late-closing fontanels, hypertelorism, early-onset cataract and mild generalized skeletal dysplasia.
Mental retardation, syndromic, Claes-Jensen type, X-linked
MedGen UID:
335139
Concept ID:
C1845243
Disease or Syndrome
) gene encoding a JmjC-domain protein with histone demethylase activity.
Mental retardation X-linked with cerebellar hypoplasia and distinctive facial appearance
MedGen UID:
336920
Concept ID:
C1845366
Disease or Syndrome
X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.
Roifman syndrome
MedGen UID:
375801
Concept ID:
C1846059
Disease or Syndrome
A rare genetic immuno-osseous dysplasia disorder with characteristics of pre and post-natal growth retardation, hypotonia, borderline to moderate intellectual disability, retinal dystrophy, spondyloepiphyseal dysplasia (epiphyseal dysplasia, epiphyses ossification delay, vertebral changes) and skeletal anomalies (brachydactyly, fifth finger clinodactyly). Also associated are humeral immunodeficiency with inability to generate specific antibodies and low circulating B-cells, craniofacial dysmorphism that typically includes microcephaly, hypertelorism, long palpebral fissures, prominent eyelashes, a narrow, tubular, upturned nose with hypoplastic alae nasi, long philtrum and thin upper lip. There is evidence the disease is caused by compound heterozygous mutation in the RNU4ATAC gene on chromosome 2q14.
Lissencephaly 2, X-linked
MedGen UID:
375832
Concept ID:
C1846171
Disease or Syndrome
A severe neurological disorder that only manifests in genotypic males and includes lissencephaly with posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset severe epilepsy, hypothalamic dysfunction including defective temperature regulation, and ambiguous genitalia with micropenis and cryptorchidism.
Simpson-Golabi-Behmel syndrome, type 2
MedGen UID:
337527
Concept ID:
C1846175
Disease or Syndrome
Simpson-Golabi-Behmel syndrome type 2 (SGBS2) is an X-linked recessive disorder in which affected males have severely impaired intellectual development, ciliary dyskinesia, and macrocephaly (summary by Budny et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of Simpson-Golabi-Behmel syndrome, see 312870.
Methylmalonic aciduria and homocystinuria type cblF
MedGen UID:
336373
Concept ID:
C1848578
Disease or Syndrome
type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.
Growth delay due to insulin-like growth factor I resistance
MedGen UID:
338622
Concept ID:
C1849157
Disease or Syndrome
Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).
Robinow syndrome, autosomal recessive
MedGen UID:
341431
Concept ID:
C1849334
Disease or Syndrome
Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS, see this term) characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia.
Ichthyosis-oral and digital anomalies syndrome
MedGen UID:
342457
Concept ID:
C1850268
Disease or Syndrome
Ichthyosis-oral and digital anomalies syndrome is characterised by ichthyosis, unusual facies (small mouth with a thin upper lip and lower lip with a midline groove) and digital anomalies (tapered fingers with a lack of distal flexion creases and wide spacing between the second and third fingers). It has been described in two sibs born to first cousin parents. Transmission appears to be autosomal recessive.
Ectodermal dysplasia syndrome with distinctive facial appearance and preaxial polydactyly of feet
MedGen UID:
342107
Concept ID:
C1851851
Disease or Syndrome
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.
Mental retardation, microcephaly, growth retardation, joint contractures, and facial dysmorphism
MedGen UID:
342889
Concept ID:
C1853480
Disease or Syndrome
Wiedemann-Steiner syndrome
MedGen UID:
340266
Concept ID:
C1854630
Disease or Syndrome
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of short stature, hypertrichosis cubiti, facial dysmorphism (hypertelorism, long eyelashes, thick eyebrows, downslanted, vertically narrow, long palpebral fissures, wide nasal bridge, broad nasal tip, long philtrum), developmental delay and mild to moderate intellectual disability. It has a variable clinical phenotype with additional manifestations reported including muscular hypotonia, patent ductus arteriosus, small hands and feet, hypertrichosis on the back and seizures. There is evidence the disease is caused by heterozygous mutation in the MLL gene on chromosome 11q23.
Kaufman oculocerebrofacial syndrome
MedGen UID:
343403
Concept ID:
C1855663
Disease or Syndrome
. An autosomal recessive mode of inheritance seems most likely.
Baraitser-Winter syndrome 1
MedGen UID:
340943
Concept ID:
C1855722
Disease or Syndrome
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability (ID) that ranges from mild (usually in those with normal brain structure) to profound (typically in those with a neuronal migration defect). Many (but not all) affected individuals have iris or retinal coloboma, sensorineural deafness, and muscle wasting resulting in a peculiar stance with kyphosis, anteverted shoulders, and slightly flexed elbows and knees. Seizures, congenital heart defects, and renal malformations also are common.
Mullerian derivatives-lymphangiectasia-polydactyly syndrome
MedGen UID:
343489
Concept ID:
C1856159
Disease or Syndrome
Müllerian derivatives-lymphangiectasia-polydactyly syndrome is characterised by prenatal linear growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, postaxial polydactyly and cryptorchidism. Mullerian duct remnants, lymphangiectasis, and renal anomalies are also present. Three cases have been described. A small penis was observed in two of these cases. The syndrome is likely to be an autosomal recessive or X-linked trait. All the reported patients died neonatally of hepatic failure.
Late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome
MedGen UID:
341663
Concept ID:
C1856969
Disease or Syndrome
Late-onset localized jonctional epidermolysis bullosa-intellectual disability syndrome is a rare junctional epidermolysis bullosa subtype characterized by late-onset blistering surrounded by erythema and localized on the anterior aspect of the lower legs, associated with dystrophic toenails, tooth enamel defects and mild to severe intellectual disability. Lens subluxation and mild facial dysmorphism (with short midface, prognatism and thin upper lip vermilion) are additional reported features. There have been no further descriptions in the literature since 1992.
Diabetes mellitus, neonatal, with congenital hypothyroidism
MedGen UID:
347541
Concept ID:
C1857775
Disease or Syndrome
encoding for the transcription factor GLI similar 3 seem to be responsible of the syndrome.
Microcephalic osteodysplastic primordial dwarfism, type 3
MedGen UID:
349167
Concept ID:
C1859439
Disease or Syndrome
Trichorhinophalangeal syndrome, type III
MedGen UID:
349899
Concept ID:
C1860823
Disease or Syndrome
Trichorhinophalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Craniofacial features include sparse, slowly growing scalp hair, laterally sparse eyebrows, a bulbous tip of the nose, protruding ears, long flat philtrum, and thin upper vermillion border. The most typical radiographic findings in TRPS are cone-shaped epiphyses, predominantly at the middle phalanges. Hip malformations such as coxa plana, coxa magna, or coxa vara are present in over 70% of patients. In older patients, the hip abnormalities resemble degenerative arthrosis. TRPS3 differs from TRPS1 by the presence of severe brachydactyly, due to short metacarpals, and severe short stature (summary by Ludecke et al., 2001).
Mental retardation, autosomal dominant 1
MedGen UID:
409857
Concept ID:
C1969562
Disease or Syndrome
An autosomal dominant condition caused by mutation(s) in the MBD5 gene, encoding methyl-CpG-binding domain protein 5. It is characterized by severe developmental and cognitive delay, short stature, craniofacial dysmorphism, and seizures.
Chromosome 10q26 deletion syndrome
MedGen UID:
436306
Concept ID:
C2674937
Disease or Syndrome
10q26 deletion syndrome is a condition that results from the loss (deletion) of a small piece of chromosome 10 in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated 10q26.The signs and symptoms of 10q26 deletion syndrome vary widely, even among affected members of the same family. Among the more common features associated with this chromosomal change are distinctive facial features, mild to moderate intellectual disability, growth problems, and developmental delay. People with 10q26 deletion syndrome often have delayed development of speech and of motor skills such as sitting, crawling, and walking. Some have limited speech throughout life. Affected individuals may experience seizures, attention-deficit/hyperactivity disorder (ADHD), poor impulse control (impulsivity), or exhibit autistic behaviors that affect communication and social interaction.A range of facial features is seen in people with 10q26 deletion syndrome, but not all affected individuals have these features. Facial features of people with 10q26 deletion syndrome may include a prominent or beaked nose, a broad nasal bridge, a small jaw (micrognathia), malformed ears that are low set, a thin upper lip, and an unusually small head size (microcephaly). Many affected individuals have widely spaced eyes (hypertelorism) that do not look in the same direction (strabismus). Some people with this condition have a short neck with extra folds of skin (webbed neck).Less common signs and symptoms can occur in 10q26 deletion syndrome. Skeletal problems include a spine that curves to the side (scoliosis), limited movement in the elbows or other joints, or curved fifth fingers and toes (clinodactyly). Slow growth before and after birth can also occur in affected individuals. Males with this condition may have genital abnormalities, such as a small penis (micropenis), undescended testes (cryptorchidism), or the urethra opening on the underside of the penis (hypospadias). Some people with 10q26 deletion syndrome have kidney abnormalities, heart defects, breathing problems, recurrent infections, or hearing or vision problems.
3q29 microdeletion syndrome
MedGen UID:
393265
Concept ID:
C2674949
Disease or Syndrome
3q29 recurrent deletion is characterized by global developmental delay and/or intellectual disability, and commonly, speech delay, and increased risk for neuropsychiatric disorders (including autism spectrum disorder, anxiety disorder, psychosis, and/or schizophrenia). Other common findings are failure to thrive and feeding problems in infancy that persist into childhood, heart defects (especially patent ductus arteriosus), gastrointestinal disorders (including gastroesophageal reflux disease), and dental abnormalities. To date findings in fewer than 50 affected individuals have been reported.
2p15-16.1 microdeletion syndrome
MedGen UID:
390902
Concept ID:
C2675875
Disease or Syndrome
2p15p16.1 microdeletion syndrome is a recently described syndrome characterized by developmental delay and facial dysmorphism.
Fontaine progeroid syndrome
MedGen UID:
394125
Concept ID:
C2676780
Disease or Syndrome
Fontaine progeroid syndrome is characterized by prenatal and postnatal growth retardation, decreased subcutaneous fat tissue, sparse hair, triangular face, widely open anterior fontanel, convex and broad nasal ridge, micrognathia, craniosynostosis in some patients, and early death in many (summary by Writzl et al., 2017).
Lymphedema, cardiac septal defects, and characteristic facies
MedGen UID:
383042
Concept ID:
C2677167
Disease or Syndrome
Lymphedema-atrial septal defects-facial changes syndrome is characterised by congenital lymphoedema of the lower limbs, atrial septal defect and a characteristic facies (a round face with a prominent forehead, a flat nasal bridge with a broad nasal tip, epicanthal folds, a thin upper lip and a cleft chin). It has been described in two brothers and a sister. Transmission appears to be autosomal recessive.
Hunter-MacDonald syndrome
MedGen UID:
383181
Concept ID:
C2677745
Disease or Syndrome
Craniofacioskeletal syndrome
MedGen UID:
394716
Concept ID:
C2678036
Disease or Syndrome
X-linked intellectual disability-craniofacioskeletal syndrome is a rare, hereditary, syndromic intellectual disability characterized by craniofacial and skeletal abnormalities in association with mild intellectual disability in females and early postnatal lethality in males. In addition to mild cognitive impairment, females present with microcephaly, short stature, skeletal features and extra temporal lobe gyrus. In males, intrauterine growth impairment, cardiac and urogenital anomalies have been reported.
Syndactyly-telecanthus-anogenital and renal malformations syndrome
MedGen UID:
394424
Concept ID:
C2678045
Disease or Syndrome
Syndrome with the association of toe syndactyly, facial dysmorphism including telecanthus and a broad nasal tip, urogenital malformations and anal atresia. Around ten cases have been reported so far. The syndrome is caused by mutations in the FAM58A gene (located on the X chromosome) encoding a protein of unknown function.
Syndromic X-linked intellectual disability Turner type
MedGen UID:
394425
Concept ID:
C2678046
Disease or Syndrome
Turner-type X-linked syndromic mental retardation (MRXST) is a neurodevelopmental disorder with a highly variable phenotype. Some affected families show X-linked recessive inheritance, with only males being affected and carrier females having no abnormal findings. In other affected families, males are severely affected, and female mutation carriers show milder cognitive abnormalities or dysmorphic features. In addition, there are female patients with de novo mutations who show the full phenotype, despite skewed X-chromosome inactivation. Affected individuals show global developmental delay from infancy, with variably impaired intellectual development and poor or absent speech, often with delayed walking. Dysmorphic features are common and can include macrocephaly, microcephaly, deep-set eyes, hypotelorism, small palpebral fissures, dysplastic, large, or low-set ears, long face, bitemporal narrowing, high-arched palate, thin upper lip, and scoliosis or mild distal skeletal anomalies, such as brachydactyly or tapered fingers. Males tend to have cryptorchidism. Other features, such as hypotonia, seizures, and delayed bone age, are more variable (summary by Moortgat et al., 2018).
Chromosome 22q11.2 deletion syndrome, distal
MedGen UID:
395634
Concept ID:
C2678480
Disease or Syndrome
Distal 22q11.2 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 22, with a highly variable phenotype characterized by prematurity, pre- and post-natal growth retardation, developmental delay (particularly speech), mild intellectual disability, variable cardiac defects, and minor skeletal anomalies (such as clinodactyly). Dysmorphic features include prominent forehead, arched eyebrows, deep set eyes, narrow upslanting palpebral fissures, ear abnormalities, hypoplastic alae nasi, smooth philtrum, down-turned mouth, thin upper lip, retro/micrognatia and pointed chin. For certain very distal deletions, there is a risk of developing malignant rhabdoid tumours.
Fibrosis of extraocular muscles, congenital, 3c
MedGen UID:
412956
Concept ID:
C2750404
Disease or Syndrome
Congenital fibrosis of the extraocular muscles (CFEOM) refers to at least eight genetically defined strabismus syndromes (CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, Tukel syndrome, and CFEOM3 with polymicrogyria) characterized by congenital non-progressive ophthalmoplegia (inability to move the eyes) with or without ptosis (droopy eyelids) affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles (superior, medial, and inferior recti, inferior oblique, and levator palpabrae superioris) and/or the trochlear nucleus and nerve (cranial nerve IV) and its innervated muscle (the superior oblique). In general, affected individuals have severe limitation of vertical gaze (usually upgaze) and variable limitation of horizontal gaze. Individuals with CFEOM frequently compensate for the ophthalmoplegia by maintaining abnormal head positions at rest and by moving their heads rather than their eyes to track objects. Individuals with CFEOM3A may also have intellectual disability, social disability, Kallmann syndrome, facial weakness, and vocal cord paralysis; and/or may develop a progressive sensorimotor axonal polyneuropathy. Individuals with Tukel syndrome also have postaxial oligodactyly or oligosyndactyly of the hands. Those with CFEOM3 with polymicrogyria also have microcephaly and intellectual disability.
ALG12-congenital disorder of glycosylation
MedGen UID:
443954
Concept ID:
C2931001
Disease or Syndrome
(22q13.33).
COG1 congenital disorder of glycosylation
MedGen UID:
443957
Concept ID:
C2931011
Disease or Syndrome
An extremely rare form of carbohydrate deficient glycoprotein syndrome with, in the few cases reported to date, variable signs including microcephaly, growth retardation, psychomotor retardation and facial dysmorphism.
Faciothoracogenital syndrome
MedGen UID:
443995
Concept ID:
C2931184
Disease or Syndrome
Brachytelephalangy with characteristic facies and kallmann syndrome
MedGen UID:
444052
Concept ID:
C2931421
Disease or Syndrome
Brachytelephalangy - dysmorphism - Kallmann syndrome is a developmental anomaly characterized by brachytelephalangy, distinct craniofacial features (prominent square forehead, telecanthus, small nose, malar hypoplasia, smooth philtrum and thin upper lip), and relative to other family members, a short stature. These features may be associated with anosmia and hypogonadotropic hypogonadism (considered as Kallman syndrome ; see this term). Brachytelephalangy - dysmorphism - Kallmann syndrome has been described in a mother and her son and there have been no further descriptions in the literature since 1986.
Opitz GBBB syndrome, type I
MedGen UID:
424842
Concept ID:
C2936904
Disease or Syndrome
X-linked Opitz G/BBB syndrome (X-OS) is a multiple-congenital-anomaly disorder characterized by facial anomalies (hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum), and laryngotracheoesophageal defects. Developmental delay and intellectual disability are observed in about 50% of affected males. Cleft lip and/or palate are present in approximately 50% of affected individuals. Other malformations (present in <50% of individuals) include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female heterozygotes usually manifest hypertelorism only.
Rett syndrome, congenital variant
MedGen UID:
462055
Concept ID:
C3150705
Disease or Syndrome
The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005).
Chromosome 6q11-q14 deletion syndrome
MedGen UID:
462140
Concept ID:
C3150790
Disease or Syndrome
The cardinal features of chromosome 6q11-q14 interstitial deletions include hypotonia, short stature, skeletal/limb anomalies, umbilical hernia, and urinary tract anomalies, as well as characteristic facial features including upslanting palpebral fissures, low-set and/or dysplastic ears, and high-arched palate (summary by Wang et al., 2009).
Ectodermal dysplasia-syndactyly syndrome 2
MedGen UID:
462159
Concept ID:
C3150809
Disease or Syndrome
Chromosome 16p12.2-p11.2 deletion syndrome, 7.1- to 8.7-MB
MedGen UID:
462208
Concept ID:
C3150858
Disease or Syndrome
16p11.2-p12.2 microdeletion syndrome is a recently described syndrome characterized by developmental delay and facial dysmorphism.
Agenesis of the corpus callosum and congenital lymphedema
MedGen UID:
462237
Concept ID:
C3150887
Disease or Syndrome
Chromosome 13q14 deletion syndrome
MedGen UID:
462652
Concept ID:
C3151302
Disease or Syndrome
Monosomy 13q14 is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the long arm of chromosome 13, characterized by developmental delay, variable degrees of intellectual disability, retinoblastoma and craniofacial dysmorphism (incl. micro/dolichocephaly, high and broad forehead, prominent eyebrows, thick, anteverted ear lobes, short nose with a broad nasal bridge and bulbous tip, prominent philtrum, large mouth with thin upper lip and thick, everted lower lip). Other features reported include high birth weight, macrocephaly, pinealoma, hepatomegaly, inguinal hernia and cryptorchidism.
N-terminal acetyltransferase deficiency
MedGen UID:
477078
Concept ID:
C3275447
Disease or Syndrome
A rare genetic progeroid syndrome with a variable phenotype including postnatal growth delay, severe global developmental delay, hypotonia, non-specific dysmorphic facies with aged appearance and cryptorchidism, as well as cardiac arrhythmia and skeletal anomalies. Patients typically present with widely opened fontanelle, mainly truncal hypotonia, waddling gait with hypertonia of the extremities, small hands and feet, broad great toes, scoliosis and redundant skin with lack of subcutaneous fat. There is evidence this disease is caused by mutation in the NAA10 gene on chromosome Xq28.
Mental retardation, autosomal dominant 7
MedGen UID:
481469
Concept ID:
C3279839
Disease or Syndrome
DYRK1A syndrome is characterized by intellectual disability including impaired speech development, autism spectrum disorder including anxious and/or stereotypic behavior problems, and microcephaly. Affected individuals often have a clinically recognizable phenotype including a typical facial gestalt, feeding problems, seizures, hypertonia, gait disturbances, and foot anomalies. The majority of affected individuals function in the moderate-to-severe range of intellectual disability; however, individuals with mild intellectual disability have also been reported. Other medical concerns relate to febrile seizures in infancy; the development of epilepsy with seizures of the atonic, absence, and generalized myoclonic types; short stature; and gastrointestinal problems. Ophthalmologic, urogenital, cardiac, and/or dental anomalies have been reported.
Geleophysic dysplasia 2
MedGen UID:
481684
Concept ID:
C3280054
Disease or Syndrome
Geleophysic dysplasia, a progressive condition resembling a lysosomal storage disorder, is characterized by short stature, short hands and feet, progressive joint limitation and contractures, distinctive facial features, progressive cardiac valvular disease, and thickened skin. Intellect is normal. Major findings are likely to be present in the first year of life. Cardiac, respiratory, and lung involvement result in death before age five years in approximately 33% of individuals with ADAMTSL2-related geleophysic dysplasia.
Mental retardation, autosomal recessive 15
MedGen UID:
481757
Concept ID:
C3280127
Disease or Syndrome
Rafiq syndrome (RAFQS) is an autosomal recessive disorder characterized by variably impaired intellectual and motor development, a characteristic facial dysmorphism, truncal obesity, and hypotonia. The facial dysmorphism comprises prominent eyebrows with lateral thinning, downward-slanting palpebral fissures, bulbous tip of the nose, large ears, and a thin upper lip. Behavioral problems, including overeating, verbal and physical aggression, have been reported in some cases. Serum transferrin isoelectric focusing shows a type 2 pattern (summary by Balasubramanian et al., 2019).
Asphyxiating thoracic dystrophy 5
MedGen UID:
482228
Concept ID:
C3280598
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
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.
Baraitser-Winter Syndrome 2
MedGen UID:
482865
Concept ID:
C3281235
Disease or Syndrome
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability (ID) that ranges from mild (usually in those with normal brain structure) to profound (typically in those with a neuronal migration defect). Many (but not all) affected individuals have iris or retinal coloboma, sensorineural deafness, and muscle wasting resulting in a peculiar stance with kyphosis, anteverted shoulders, and slightly flexed elbows and knees. Seizures, congenital heart defects, and renal malformations also are common.
Hypertelorism and other facial dysmorphism, brachydactyly, genital abnormalities, mental retardation, 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.
Mitochondrial pyruvate carrier deficiency
MedGen UID:
766521
Concept ID:
C3553607
Disease or Syndrome
Mitochondrial pyruvate carrier deficiency is an autosomal recessive metabolic disorder characterized by delayed psychomotor development and lactic acidosis with a normal lactate/pyruvate ratio resulting from impaired mitochondrial pyruvate oxidation (summary by Bricker et al., 2012).
Schuurs-hoeijmakers syndrome
MedGen UID:
767257
Concept ID:
C3554343
Disease or Syndrome
An autosomal dominant condition caused by mutation(s) in the PACS1 gene, encoding phosphofurin acidic cluster sorting protein 1. It is characterized by intellectual developmental delay, craniofacial abnormalities, as well as other variable congenital abnormalities.
Congenital disorder of glycosylation type 1u
MedGen UID:
767299
Concept ID:
C3554385
Disease or Syndrome
Congenital muscular dystrophy with intellectual disability and severe epilepsy is a rare, fatal, inborn error of metabolism disorder characterized by respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic fascies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated.
Mental retardation, autosomal dominant 18
MedGen UID:
767362
Concept ID:
C3554448
Disease or Syndrome
GAND syndrome is a neurodevelopmental syndrome characterized by global developmental delay apparent from infancy, with motor delay and moderate to severely impaired intellectual development. Most patients have poor speech acquisition, especially expressive language development, and may manifest signs of speech apraxia. Affected individuals have hypotonia and feeding difficulties in infancy, as well as common dysmorphic features, such as macrocephaly, frontal bossing, hypertelorism, deep-set eyes, posteriorly rotated ears, and elongated wide nose with prominent nasal tip. More variable features may include seizures, cardiac abnormalities, and nonspecific findings on brain imaging (summary by Shieh et al., 2020).
Mental retardation, autosomal dominant 19
MedGen UID:
767363
Concept ID:
C3554449
Disease or Syndrome
Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Many patients have visual abnormalities, ranging from strabismus to optic nerve atrophy and retinal abnormalities. Affected individuals also develop spasticity, particularly of the lower limbs, and may have behavioral abnormalities (summary by Kuechler et al., 2015 and Kharbanda et al., 2017).
Mental retardation, autosomal recessive 35
MedGen UID:
767523
Concept ID:
C3554609
Disease or Syndrome
Short ulna-dysmorphism-hypotonia-intellectual disability syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by mild to severe global development delay, severe intellectual disability, mild hypotonia, a short ulna, hirsutism of the face and extremities, minimal scoliosis, and facial dysmorphism, notably a tall broad forehead, synophrys, hypertelorism, malar hypoplasia, broad nose with thick alae nasi, low-set, small ears, long philtrum, thin upper lip and everted lower lip vermilion.
Axenfeld-Rieger syndrome type 1
MedGen UID:
811487
Concept ID:
C3714873
Disease or Syndrome
A rare autosomal dominant syndrome linked to mutations in the PITX2 gene. It is characterized by abnormalities in the anterior chamber of the eye and underdevelopment of the teeth.
Mental retardation, autosomal dominant 22
MedGen UID:
814514
Concept ID:
C3808184
Disease or Syndrome
MRD22 is characterized by impaired intellectual development with frequent cooccurrence of corpus callosum anomalies, hypotonia, microcephaly, growth problems, and variable facial dysmorphism (summary by van der Schoot et al., 2018). Chromosome 1q43-q44 deletion syndrome is characterized by moderate to severe mental retardation, limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures. The phenotype is variable, and not all features are observed in all patients, which may be explained in some cases by incomplete penetrance or variable expressivity (summary by Ballif et al., 2012).
Hypotonia, infantile, with psychomotor retardation and characteristic facies 1
MedGen UID:
815784
Concept ID:
C3809454
Disease or Syndrome
Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. Affected individuals show very poor, if any, normal cognitive development. Some patients are never learn to sit or walk independently (summary by Al-Sayed et al., 2013). Genetic Heterogeneity of Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies See also IHPRF2 (616801), caused by mutation in the UNC80 gene (612636) on chromosome 2q34; and IHPRF3 (616900), caused by mutation in the TBCK gene (616899) on chromosome 4q24.
Verheij syndrome
MedGen UID:
816353
Concept ID:
C3810023
Disease or Syndrome
A multiple congenital anomalies/dysmorphic - intellectual disability syndrome characterized by feeding problems, growth retardation, microcephaly, developmental delay, digital and vertebral anomalies, joint laxity/dislocation, cardiac and renal defects, and dysmorphic facial features (including plagiocephaly, prominent forehead, bitemporal narrowing, bilateral coloboma, epicanthal folds, malformations of the outer and middle ear, wide nasal bridge, anteverted nares, prominent and bulbous nose tip, long philtrum, thin lips, high and narrow palate, micrognathia with prognathism/retrognathism, full cheeks, and short, broad neck). Additional variable manifestations include obstructive apneas, recurrent pneumonia, and seizures.
Hyperphosphatasia with mental retardation syndrome 4
MedGen UID:
816684
Concept ID:
C3810354
Disease or Syndrome
Hyperphosphatasia with mental retardation syndrome-4 is an autosomal recessive neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase (summary by Howard et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Mental retardation, autosomal dominant 23
MedGen UID:
816736
Concept ID:
C3810406
Disease or Syndrome
Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency is a rare, syndromic intellectual disability characterized by intellectual disability of various severity, hypotonia, feeding difficulties, dysmorphic features, autism and behavioral issues. Growth retardation, congenital heart anomalies, gastrointestinal and genitourinary defects have been rarely associated.
Pontocerebellar hypoplasia, type 10
MedGen UID:
862784
Concept ID:
C4014347
Disease or Syndrome
Pontocerebellar hypoplasia type 10 is a rare, genetic, pontocerebellar hypoplasia subtype characterized by severe psychomotor developmental delay, progressive microcephaly, progressive spasticity, seizures, and brain abnormalities consisting of mild atrophy of the cerebellum, pons and corpus callosum and cortical atrophy with delayed myelination. Patients may present dysmorphic facial features (high arched eyebrows, prominent eyes, long palpebral fissures and eyelashes, broad nasal root, and hypoplastic alae nasi) and an axonal sensorimotor neuropathy.
Helsmoortel-Van der Aa Syndrome
MedGen UID:
862975
Concept ID:
C4014538
Disease or Syndrome
A rare syndromic intellectual disability characterized by global developmental delay, gastrointestinal problems, hypotonia, delayed speech, behavioral and sleep problems, pain insensitivity, seizures, structural brain anomalies, dysmorphic features, visual problems, early tooth eruption and autistic features.
Immunodeficiency 26 with or without neurologic abnormalities
MedGen UID:
863270
Concept ID:
C4014833
Disease or Syndrome
Severe combined immunodeficiency (SCID) due to DNA-PKcs deficiency is an extremely rare type of SCID (see this term) characterized by the classical signs of SCID (severe and recurrent infections, diarrhea, failure to thrive), absence of T and B lymphocytes, and cell sensitivity to ionizing radiation.
Mental retardation, autosomal dominant 29
MedGen UID:
863578
Concept ID:
C4015141
Disease or Syndrome
SETBP1 disorder is a condition that involves speech and language problems, intellectual disability, and distinctive facial features.In people with SETBP1 disorder, problems with expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech). Speech development may be limited to a few words or no speech. Affected individuals often communicate using gestures or by mimicking the expressions of others.Individuals with SETBP1 disorder have intellectual disability that can range from mild to moderate. They may also have behavioral problems, such as attention-deficit/hyperactivity disorder (ADHD) or autistic behaviors that affect communication and social interaction. Affected individuals may have weak muscle tone (hypotonia); delayed development of motor skills, such as sitting, standing, and walking; or recurrent seizures (epilepsy).Distinctive facial features in people with SETBP1 disorder can include a long face, a high forehead, eyebrows that grow together in the middle (synophrys), short eye openings (short palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), droopy eyelids (ptosis), puffiness of the skin around the eyes (periorbital fullness), small nostrils, a high nasal bridge, a broad tip of the nose, a thin upper lip, a high arch in the roof of the mouth (high-arched palate), and a small chin.
Peroxisomal fatty acyl-coa reductase 1 disorder
MedGen UID:
863781
Concept ID:
C4015344
Disease or Syndrome
A rare disorder of plasmalogen biosynthesis characterized by syndromic severe intellectual disability with congenital cataracts, early-onset epilepsy, microcephaly, global developmental delay, growth retardation and short stature, and spastic quadriparesis. Dysmorphic facial features may be present, including high-arched eyebrows, flattened nasal root, hypertelorism, and long and smooth philtrum. Rhizomelia is not part of the syndrome. Cerebellar atrophy, white matter abnormalities, and Dandy-Walker malformation have been described on brain imaging.
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset
MedGen UID:
864165
Concept ID:
C4015728
Disease or Syndrome
A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by global developmental delay, postnatal microcephaly, intellectual disability, ataxia, sensorineural hearing loss, and exocrine pancreatic insufficiency. More variable manifestations include hypotonia, growth retardation, peripheral demyelinating neuropathy, dysmorphic facial features, and additional endocrine abnormalities. Brain imaging may show progressive cerebellar atrophy in some patients.
Al-Raqad syndrome
MedGen UID:
897610
Concept ID:
C4085595
Disease or Syndrome
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2
MedGen UID:
907651
Concept ID:
C4225203
Disease or Syndrome
UNC80 deficiency is characterized by hypotonia, strabismus, oral motor dysfunction, postnatal growth deficiency, and developmental delay. The majority of individuals do not learn to walk. All individuals lack expressive language; however, many have expressive body language, and a few have used signs to communicate. Seizures may develop during infancy or childhood. Additional features can include nystagmus, extremity hypertonia, a high-pitched cry, repetitive and self-stimulatory behaviors, constipation, clubfeet, joint contractures, and scoliosis. For most individuals the UNC80 deficiency syndrome is not progressive. Individuals have slow acquisition of skills and do not have a loss of skills suggestive of neurodegeneration.
Takenouchi-Kosaki syndrome
MedGen UID:
906646
Concept ID:
C4225222
Disease or Syndrome
A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by global developmental delay, intellectual disability, macrothrombocytopenia, lymphedema, and dysmorphic facial features (like synophrys, ptosis, eversion of the lateral portion of the lower eyelid, and thin upper lip, among others). Additional reported manifestations include cardiac and genitourinary anomalies, sensorineural hearing loss, ophthalmologic abnormalities, skeletal anomalies, and immunodeficiency. Brain imaging may show enlarged ventricles, cerebellar atrophy, or white matter changes.
Cleft palate, psychomotor retardation, and distinctive facial features
MedGen UID:
895943
Concept ID:
C4225229
Disease or Syndrome
Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, axial hypotonia, palate abnormalities (including cleft palate and/or high and narrow palate), dysmorphic facial features (including prominent forehead, hypertelorism, downslanting palpebral fissures, wide nasal bridge, thin lips and widely spaced teeth), and short stature. Additional manifestations may include digital anomalies (such as brachydactyly, clinodactyly, and hypoplastic toenails), a single palmar crease, lower limb hypertonia, joint hypermobility, as well as ocular and urogenital anomalies.
Desanto-shinawi syndrome
MedGen UID:
908218
Concept ID:
C4225239
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.
Yuan-Harel-Lupski syndrome
MedGen UID:
894862
Concept ID:
C4225255
Disease or Syndrome
Yuan-Harel-Lupski syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and early-onset peripheral neuropathy. The disorder comprises features of both demyelinating Charcot-Marie-Tooth disease type 1A (CMT1A; 118220), which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome (PTLS; 610883), which results from duplication of a slightly proximal region on 17p11.2 that includes the RAI1 gene. These 2 loci are about 2.5 Mb apart. The resultant YUHAL phenotype may be more severe in comparison to the individual contributions of each gene, with particularly early onset of peripheral neuropathy and features of both central and peripheral nervous system involvement (summary by Yuan et al., 2015).
Smith-Kingsmore syndrome
MedGen UID:
899689
Concept ID:
C4225259
Disease or Syndrome
A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability, characterized by macrocephaly, intellectual disability, seizures, dysmorphic facial features (including tall forehead, downslanting palpebral fissures, hypertelorism, depressed nasal bridge, and macrostomia), megalencephaly, and small thorax. Other reported features are umbilical hernia, muscular hypotonia, global developmental delay, autistic behavior, and café-au-lait spots, among others.
Kosaki overgrowth syndrome
MedGen UID:
896409
Concept ID:
C4225270
Disease or Syndrome
Kosaki overgrowth syndrome is characterized by a facial gestalt involving prominent forehead, proptosis, downslanting palpebral fissures, broad nasal bridge, thin upper lip, and pointed chin. Affected individuals are tall, with an elongated lower segment, hands, and feet. Skin is hyperelastic and fragile, and there is progressive neurologic deterioration with white matter lesions on brain imaging (Takenouchi et al., 2015).
Klippel-feil syndrome 4, autosomal recessive, with nemaline myopathy and facial dysmorphism
MedGen UID:
894399
Concept ID:
C4225285
Disease or Syndrome
Klippel-Feil syndrome-4 with nemaline myopathy and facial dysmorphism is an autosomal recessive disorder characterized mainly by severe hypotonia apparent from infancy. Klippel-Feil anomaly is primarily defined by fusion of the cervical spine, with associated low posterior hairline and limited neck mobility being observed in about half of patients (summary by Alazami et al., 2015). For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Lethal congenital contracture syndrome 9
MedGen UID:
903881
Concept ID:
C4225303
Disease or Syndrome
Robinow syndrome, autosomal dominant 2
MedGen UID:
897039
Concept ID:
C4225363
Disease or Syndrome
Autosomal dominant Robinow syndrome (ADRS) is characterized by skeletal findings (short stature, mesomelic limb shortening predominantly of the upper limbs, and brachydactyly), genital abnormalities (in males: micropenis / webbed penis, hypoplastic scrotum, cryptorchidism; in females: hypoplastic clitoris and labia majora), dysmorphic facial features (widely spaced and prominent eyes, frontal bossing, anteverted nares, midface retrusion), dental abnormalities (including malocclusion, crowding, hypodontia, late eruption of permanent teeth), bilobed tongue, and occasional prenatal macrocephaly that persists postnatally. Less common findings include renal anomalies, radial head dislocation, vertebral abnormalities such as hemivertebrae and scoliosis, nail dysplasia, cardiac defects, cleft lip/palate, and (rarely) cognitive delay. When present, cardiac defects are a major cause of morbidity and mortality. A variant of Robinow syndrome, associated with osteosclerosis and caused by a heterozygous pathogenic variant in DVL1, is characterized by normal stature, persistent macrocephaly, increased bone mineral density with skull osteosclerosis, and hearing loss, in addition to the typical features described above.
Mental retardation, autosomal dominant 32
MedGen UID:
903767
Concept ID:
C4225396
Disease or Syndrome
Arboleda-Tham syndrome (ARTHS) is an autosomal dominant disorder with the core features of impaired intellectual development, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications (summary by Kennedy et al., 2019).
Mental retardation, X-linked, syndromic 33
MedGen UID:
895979
Concept ID:
C4225418
Disease or Syndrome
X-linked syndromic mental retardation-33 is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015).
Chromosome 10q22.3-q23.2 deletion syndrome
MedGen UID:
906099
Concept ID:
C4225669
Disease or Syndrome
10q22.3q23.3 microdeletion syndrome is a rare partial autosomal monosomy characterized by a mild facial dysmorphism variably including macrocephaly, broad forehead, hypertelorism or hypotelorism, deep-set eyes, upslanting or downslanting palpebral fissures, low-set ears, flat nasal bridge, smooth philtrum, thin upper lip), cleft palate, cerebellar and cardiac malformations, psychomotor development delay, and behavioral abnormalities (attention deficit hyperactivity disorder, autism). Other rare features may include congenital breast aplasia, arachnodactyly, joint hyperlaxity, club feet, feeding difficulties, failure to thrive.
Ehlers-Danlos syndrome, musculocontractural type
MedGen UID:
929456
Concept ID:
C4303787
Disease or Syndrome
A form of Ehlers-Danlos syndrome (EDS) with characteristics of distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adducted thumb, talipes equinovarus, haemorrhagic diathesis and multisystem fragility-related manifestations.
Hypotonia, ataxia, and delayed development syndrome
MedGen UID:
934585
Concept ID:
C4310618
Disease or Syndrome
Hypotonia, ataxia, and delayed development syndrome (HADDS) is a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia. Some patients may have urogenital abnormalities (summary by Sleven et al., 2017).
Arthrogryposis, distal, with impaired proprioception and touch
MedGen UID:
934659
Concept ID:
C4310692
Disease or Syndrome
Distal arthrogryposis with impaired proprioception and touch is an autosomal recessive neurologic disorder characterized by loss of certain mechanosensation modalities resulting in ataxia, difficulty walking, dysmetria, muscle weakness and atrophy, and progressive skeletal contractures. Patients have onset of symptoms in early childhood (summary by Chesler et al., 2016 and Delle Vedove et al., 2016).
ZTTK syndrome
MedGen UID:
934663
Concept ID:
C4310696
Disease or Syndrome
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by developmental delay and intellectual disability associated with brain malformations (including abnormal gyration patterns, ventriculomegaly, white matter abnormalities and hypoplasia of the corpus callosum and cerebellar hemispheres), facial dysmorphisms (including facial asymmetry, midface retraction, deep-set eyes, downslanting palpebral fissures, low-set ears, broad and depressed nasal bridge, short philtrum) and musculoskeletal abnormalities (including hemivertebrae, scoliosis or kyphosis, contractures, and joint laxity). Additional clinical manifestations include seizures, strabismus, vision loss, urogenital malformations, heart defects and short stature.
Alazami-Yuan syndrome
MedGen UID:
934669
Concept ID:
C4310702
Disease or Syndrome
Okur-chung neurodevelopmental syndrome
MedGen UID:
934706
Concept ID:
C4310739
Disease or Syndrome
Okur-Chung neurodevelopmental syndrome is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability with poor speech, behavioral abnormalities, cortical malformations in some patients, and variable dysmorphic facial features. Additional features, including microcephaly, gastrointestinal problems, and low levels of immunoglobulins, may be observed in some patients (Okur et al., 2016).
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).
Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
MedGen UID:
934777
Concept ID:
C4310810
Disease or Syndrome
Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis is an X-linked recessive disorder with onset of features in early childhood. Anemia is sometimes present. Some patients may show mild early motor or speech delay, but cognition is normal (summary by Andreoletti et al., 2017).
Intellectual developmental disorder with persistence of fetal hemoglobin
MedGen UID:
934800
Concept ID:
C4310833
Disease or Syndrome
BCL11A-related intellectual disability (BCL11A-ID) is characterized by developmental delay / intellectual disability of variable degree, neonatal hypotonia, microcephaly, distinctive but variable facial characteristics, behavior problems, and asymptomatic persistence of fetal hemoglobin. Growth delay, seizures, and autism spectrum disorder have also been reported in some affected individuals.
MENTAL RETARDATION, X-LINKED, SYNDROMIC, 35
MedGen UID:
1392054
Concept ID:
C4478383
Disease or Syndrome
Brain malformations and urinary tract defects
MedGen UID:
1392440
Concept ID:
C4478940
Congenital Abnormality
1p31p32 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome 1, characterized by developmental delay, corpus callosum agenesis/hypoplasia and craniofacial dysmorphism, such as macrocephaly (caused by hydrocephalus or ventriculomegaly), low-set ears, anteverted nostrils and micrognathia. Urinary tract defects (e.g. vesicoureteral reflux, urinary incontinence) are also frequently associated. Other reported variable manifestations include hypotonia, tethered spinal cord, Chiari type I malformation and seizures.
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.
Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold
MedGen UID:
1385744
Concept ID:
C4479517
Disease or Syndrome
Jansen-de Vries syndrome (JDVS) is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with speech delay, and behavioral abnormalities. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold and/or hypersensitivity to sound, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet (summary by Jansen et al., 2017).
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies
MedGen UID:
1375601
Concept ID:
C4479520
Disease or Syndrome
IDDFSDA is an autosomal recessive severe multisystem disorder characterized by poor overall growth, developmental delay, early-onset seizures, intellectual disability, and dysmorphic features. There is phenotypic variability. The most severely affected patients have a neurodevelopmental disorder with microcephaly, absent speech, and inability to walk, and they require feeding tubes. Some patients have congenital heart defects or nonspecific abnormalities on brain imaging. Less severely affected individuals have mild to moderate intellectual disability with normal speech and motor development (summary by Santiago-Sim et al., 2017).
Neurodevelopmental disorder with midbrain and hindbrain malformations
MedGen UID:
1385580
Concept ID:
C4479613
Disease or Syndrome
Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
MedGen UID:
1612119
Concept ID:
C4539968
Disease or Syndrome
CAKUTHED is an autosomal dominant highly pleiotropic developmental disorder characterized mainly by variable congenital anomalies of the kidney and urinary tract, sometimes resulting in renal dysfunction or failure, dysmorphic facial features, and abnormalities of the outer ear, often with hearing loss. Most patients have global developmental delay (summary by Heidet et al., 2017 and Slavotinek et al., 2017).
Al Kaissi syndrome
MedGen UID:
1611968
Concept ID:
C4540156
Disease or Syndrome
Al Kaissi syndrome is an autosomal recessive developmental disorder characterized by growth retardation, spine malformation, particularly of the cervical spine, dysmorphic facial features, and delayed psychomotor development with moderate to severe intellectual disability (summary by Windpassinger et al., 2017).
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
MedGen UID:
1627464
Concept ID:
C4540327
Disease or Syndrome
NEDDFL is a neurodevelopmental disorder characterized by delayed psychomotor development and intellectual disability, poor growth with small head size, dysmorphic facial features, and mild abnormalities of the hands and feet (summary by Stankiewicz et al., 2017).
Retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome
MedGen UID:
1615526
Concept ID:
C4540367
Disease or Syndrome
SHRF is an autosomal recessive disorder characterized by short stature, brachydactyly, dysmorphic facial features, hearing loss, and visual impairment. Onset of the hearing and visual abnormalities, including retinitis pigmentosa, varies from birth to the second decade. Patients have mild intellectual disability and mild cerebellar atrophy with myelination defects on brain imaging (summary by Di Donato et al., 2016).
Robinow syndrome, autosomal dominant 1
MedGen UID:
1641736
Concept ID:
C4551475
Disease or Syndrome
Autosomal dominant Robinow syndrome (ADRS) is characterized by skeletal findings (short stature, mesomelic limb shortening predominantly of the upper limbs, and brachydactyly), genital abnormalities (in males: micropenis / webbed penis, hypoplastic scrotum, cryptorchidism; in females: hypoplastic clitoris and labia majora), dysmorphic facial features (widely spaced and prominent eyes, frontal bossing, anteverted nares, midface retrusion), dental abnormalities (including malocclusion, crowding, hypodontia, late eruption of permanent teeth), bilobed tongue, and occasional prenatal macrocephaly that persists postnatally. Less common findings include renal anomalies, radial head dislocation, vertebral abnormalities such as hemivertebrae and scoliosis, nail dysplasia, cardiac defects, cleft lip/palate, and (rarely) cognitive delay. When present, cardiac defects are a major cause of morbidity and mortality. A variant of Robinow syndrome, associated with osteosclerosis and caused by a heterozygous pathogenic variant in DVL1, is characterized by normal stature, persistent macrocephaly, increased bone mineral density with skull osteosclerosis, and hearing loss, in addition to the typical features described above.
Hyperphosphatasia with mental retardation syndrome 1
MedGen UID:
1647044
Concept ID:
C4551502
Disease or Syndrome
Hyperphosphatasia with mental retardation syndrome-1 is an autosomal recessive disorder characterized by mental retardation, various neurologic abnormalities such as seizures and hypotonia, and hyperphosphatasia. Other features include facial dysmorphism and variable degrees of brachytelephalangy (summary by Krawitz et al., 2010). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (610293). Genetic Heterogeneity of Hyperphosphatasia with Mental Retardation Syndrome See also HPMRS2 (614749), caused by mutation in the PIGO gene (614730) on chromosome 9p13; HPMRS3 (614207), caused by mutation in the PGAP2 gene (615187) on chromosome 11p15; HPMRS4 (615716), caused by mutation in the PGAP3 gene (611801) on chromosome 17q12; HPMRS5 (616025), caused by mutation in the PIGW gene (610275) on chromosome 17q12; and HPMRS6 (616809), caused by mutation in the PIGY gene (610662) on chromosome 4q22. Knaus et al. (2018) provided a review of the main clinical features of the different types of HPMRS, noting that some patients have a distinct pattern of facial anomalies that can be detected by computer-assisted comparison, particularly those with mutations in the PIGV and PGAP3 genes. Individuals with HPMRS have variable increased in alkaline phosphatase (AP) as well as variable decreases in GPI-linked proteins that can be detected by flow cytometry. However, there was no clear correlation between AP levels or GPI-linked protein abnormalities and degree of neurologic involvement, mutation class, or gene involved. Knaus et al. (2018) concluded that a distinction between HPMRS and MCAHS (see, e.g., 614080), which is also caused by mutation in genes involved in GPI biosynthesis, may be artificial and even inaccurate, and that all these disorders should be considered and classified under the more encompassing term of 'GPI biosynthesis defects' (GPIBD).
Cornelia de Lange syndrome 1
MedGen UID:
1645760
Concept ID:
C4551851
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, autosomal dominant 56
MedGen UID:
1638835
Concept ID:
C4693389
Mental or Behavioral Dysfunction
Short-rib thoracic dysplasia 18 with polydactyly
MedGen UID:
1632904
Concept ID:
C4693420
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia with or without polydactyly, see SRTD1 (208500).
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies
MedGen UID:
1635916
Concept ID:
C4693481
Disease or Syndrome
Patients with SSFSC1 have short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract (Tan et al., 2017). Genetic Heterogeneity of Short Stature, Facial Dysmorphism, and Skeletal Anomalies With or Without Cardiac Anomalies SSFSC2 (619184) is caused by mutation in the SCUBE3 gene (614708) on chromosome 6p21.
Chromosome 1p35 deletion syndrome
MedGen UID:
1632676
Concept ID:
C4693669
Disease or Syndrome
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.
Ververi-Brady syndrome
MedGen UID:
1647785
Concept ID:
C4693824
Disease or Syndrome
Ververi-Brady syndrome is characterized by mild developmental delay, mildly impaired intellectual development and speech delay, and mild dysmorphic facial features. Affected individuals can usually attend mainstream schools with support, and may also show autistic features (summary by Ververi 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.
Coffin-Siris syndrome 7
MedGen UID:
1648281
Concept ID:
C4747954
Disease or Syndrome
Coffin-Siris syndrome-7 is an autosomal dominant neurodevelopmental disorder characterized by global developmental delay with mild to moderate intellectual disability, speech impairment, behavioral abnormalities, poor overall growth, coarse facial features, and hypoplastic fifth toenails (summary by Vasileiou et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Developmental and epileptic encephalopathy, 66
MedGen UID:
1648486
Concept ID:
C4748070
Disease or Syndrome
Developmental and epileptic encephalopathy-66 (DEE66) is a neurologic disorder characterized by the onset of various types of seizures in the first days or weeks of life. Most seizures have focal origins; secondary generalization is common. Seizure control is difficult at first, but may become easier with time. Affected individuals show global developmental delay with hypotonia, behavioral abnormalities, and dysmorphic features or ophthalmologic defects. Brain imaging often shows cerebellar dysgenesis. A subset of patients have extraneurologic manifestations, including hematologic and distal limb abnormalities (summary by Olson et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities
MedGen UID:
1648327
Concept ID:
C4748152
Disease or Syndrome
Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome
MedGen UID:
1648431
Concept ID:
C4748715
Disease or Syndrome
A rare genetic neurological disorder characterized by infantile hypotonia, congenital ophthalmic anomalies (including strabismus, esotropia, nystagmus, and central visual impairment), global developmental delay and intellectual disability, behavioral abnormalities, and movement disorder (such as dystonia, chorea, hyperkinesia, stereotypies). Mild facial dysmorphism and skeletal deformities have also been reported. EEG testing shows marked abnormalities in the absence of overt epileptic seizures.
X-linked intellectual disability-hypotonic face syndrome
MedGen UID:
1676827
Concept ID:
C4759781
Disease or Syndrome
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is characterized by distinctive craniofacial features, genital anomalies, hypotonia, and mild-to-profound developmental delay / intellectual disability (DD/ID). Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short triangular nose, tented upper lip, and thick or everted lower lip with coarsening of the facial features over time. While all affected individuals have a normal 46,XY karyotype, genital anomalies comprise a range from hypospadias and undescended testicles, to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Alpha-thalassemia, observed in about 75% of affected individuals, is mild and typically does not require treatment. Osteosarcoma has been reported in a few males with germline pathogenic variants.
Mullegama-Klein-Martinez syndrome
MedGen UID:
1683985
Concept ID:
C5193008
Disease or Syndrome
Intellectual developmental disorder, X-linked 108
MedGen UID:
1680544
Concept ID:
C5193009
Disease or Syndrome
Intellectual developmental disorder with cardiac defects and dysmorphic facies
MedGen UID:
1675627
Concept ID:
C5193024
Disease or Syndrome
A rare, genetic, neurodevelopmental disorder characterized by global developmental delay, congenital heart defects, generalized hypertrichosis and dysmorphic facial features, most commonly triangular face, thick arched eyebrows, widely spaced eyes, posteriorly rotated low set ears, depressed nasal bridge, broad nasal root and tip, and pointed chin.
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).
Menke-Hennekam syndrome 2
MedGen UID:
1676668
Concept ID:
C5193035
Disease or Syndrome
Menke-Hennekam syndrome-2 (MKHK2) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, and hearing impairment are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-2 (RSTS2; 613684), patients with MKHK1 do not resemble the striking phenotype of RSTS2. For a discussion of genetic heterogeneity of Menke-Hennekam syndrome, see MKHK1 (618332).
Coffin-Siris syndrome 8
MedGen UID:
1679527
Concept ID:
C5193054
Disease or Syndrome
Coffin-Siris syndrome-8 is characterized by variable degrees of impaired intellectual development including speech impairment, hypotonia, feeding difficulties, and behavioral abnormalities. Dysmorphic features may or may not be present and include hypertrichosis or thin scalp hair, thick eyebrows, thin upper vermilion, and upturned nose (Machol et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Turnpenny-fry syndrome
MedGen UID:
1683283
Concept ID:
C5193060
Disease or Syndrome
Turnpenny-Fry syndrome (TPFS) is characterized by developmental delay, impaired intellectual development, impaired growth, and recognizable facial features that include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic 'satyr' ears. Other common findings include feeding problems, constipation, and a range of brain, cardiac, vascular, and skeletal malformations (Turnpenny et al., 2018).
Developmental delay with variable intellectual impairment and behavioral abnormalities
MedGen UID:
1676192
Concept ID:
C5193092
Disease or Syndrome
Developmental delay with variable intellectual impairment and behavioral abnormalities (DDVIBA) is an autosomal dominant neurodevelopmental disorder. Most patients have impaired intellectual development with speech difficulties, and many have behavioral abnormalities, most commonly autism spectrum disorder (ASD), defects in attention, and/or hyperactivity. Many patients have dysmorphic features, although there is not a consistent gestalt. Additional more variable features may include hypotonia, somatic overgrowth with macrocephaly, mild distal skeletal anomalies, sleep disturbances, movement disorders, and gastrointestinal issues, such as constipation. The phenotype is highly variable (summary by Vetrini et al., 2019 and Torti et al., 2019).
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).
Developmental delay with or without dysmorphic facies and autism
MedGen UID:
1679263
Concept ID:
C5193106
Disease or Syndrome
Developmental delay with or without dysmorphic facies and autism (DEDDFA) is a complex neurodevelopmental disorder apparent from infancy or early childhood and associated with variably impaired intellectual development. Some patients may be severely affected with no speech and inability to walk, whereas others may be able to attend special schools or have normal intellectual function associated with autism spectrum disorder and mild speech delay. Genetic analysis has suggested that the phenotype can be broadly categorized into 2 main groups. Patients with TRRAP mutations affecting residues 1031-1159 have a more severe disorder, often with multisystem involvement, including renal, cardiac, and genitourinary systems, as well as structural brain abnormalities. Patients with mutations outside of that region tend to have a less severe phenotype with a higher incidence of autism and usually no systemic involvement. Patients in both groups usually have somewhat similar dysmorphic facial features, such as upslanting palpebral fissures, hypertelorism, low-set ears, and broad or depressed nasal bridge, although these features are highly variable (summary by Cogne et al., 2019).
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
MedGen UID:
1674629
Concept ID:
C5193125
Disease or Syndrome
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA) is a syndromic neurodevelopmental disorder characterized by severe global developmental delay, impaired intellectual development with poor or absent language, significant motor disability with inability to walk, dysmorphic facial features, skeletal anomalies, and variable congenital anomalies. Most patients also have seizures and structural brain abnormalities (summary by Palmer et al., 2019).
Stargardt macular degeneration, absent or hypoplastic corpus callosum, mental retardation, and dysmorphic features
MedGen UID:
1680314
Concept ID:
C5193232
Disease or Syndrome
Intellectual developmental disorder 61
MedGen UID:
1684867
Concept ID:
C5231400
Disease or Syndrome
Autosomal dominant intellectual developmental disorder-61 (MRD61) is characterized by global developmental delay apparent in infancy with mildly impaired intellectual development, expressive speech delay, and behavioral abnormalities, including autism spectrum disorder and attention deficit-hyperactivity disorder (ADHD). Most affected individuals learn to walk on time or with some mild delay. Additional features are highly variable and may include nonspecific dysmorphic features, obstipation, ocular anomalies, and poor overall growth (Snijders Blok et al., 2018).
Neurodevelopmental disorder with visual defects and brain anomalies
MedGen UID:
1684774
Concept ID:
C5231404
Disease or Syndrome
Neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA) is characterized by global developmental delay with impaired intellectual development and speech delay, variable visual defects, including retinitis pigmentosa and optic atrophy, hypotonia or hypertonia, and variable structural brain abnormalities. Other nonspecific features may be found (summary by Okur et al., 2019).
Developmental and epileptic encephalopathy, 77
MedGen UID:
1684735
Concept ID:
C5231405
Disease or Syndrome
Multiple congenital anomalies-hypotonia-seizures syndrome-4 (MCAHS4) is an autosomal recessive neurologic disorder characterized by onset of refractory seizures in the first months of life. Patients have severe global developmental delay, and may have additional variable features, including dysmorphic or coarse facial features, visual defects, and mild skeletal or renal anomalies. At the cellular level, the disorder is caused by a defect in the synthesis of glycosylphosphatidylinositol (GPI), and thus affects the expression of GPI-anchored proteins at the cell surface (summary by Starr et al., 2019). For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080). For a discussion of genetic heterogeneity of DEE, see 308350. For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Glycosylphosphatidylinositol biosynthesis defect 21
MedGen UID:
1684749
Concept ID:
C5231419
Disease or Syndrome
Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis (NEDBSS) is an autosomal recessive disorder characterized by severely impaired psychomotor development, hypotonia, seizures, and structural brain anomalies, including thin corpus callosum and cerebellar atrophy. Other features include scoliosis, dysmorphic facies, and visual impairment. Affected individuals are usually unable to walk or speak and may require tube feeding in severe cases. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis (summary by Knaus et al., 2019). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Pontocerebellar hypoplasia, type 13
MedGen UID:
1684708
Concept ID:
C5231425
Disease or Syndrome
Pontocerebellar hypoplasia type 13 (PCH13) is an autosomal recessive disorder characterized by global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable (summary by Uwineza et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596).
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).
Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
MedGen UID:
1684840
Concept ID:
C5231431
Disease or Syndrome
Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA) is an autosomal recessive disorder characterized by severe global developmental delay, usually with hypotonia and absence of spontaneous movements other than head control, impaired intellectual development with absent speech, distal contractures, progressive microcephaly, dysmorphic features, and distal skeletal abnormalities, such as rocker-bottom feet and clenched hands with camptodactyly. Brain imaging tends to show a simplified gyral pattern of the cerebral cortex, delayed myelination, thin corpus callosum, and hypoplasia of the brainstem and cerebellum. The disorder may be complicated by feeding and/or breathing difficulties, often resulting in death in infancy (summary by Magini et al., 2019).
Intellectual developmental disorder, autosomal recessive 72
MedGen UID:
1684805
Concept ID:
C5231452
Disease or Syndrome
Liang-Wang syndrome
MedGen UID:
1684847
Concept ID:
C5231479
Disease or Syndrome
Liang-Wang syndrome (LIWAS) is a polymalformation syndrome apparent from birth that shows large phenotypic variability and severity. However, all patients have some degree of neurologic dysfunction. The most severely affected individuals have severe global developmental delay with impaired intellectual development and poor or absent speech, marked craniofacial dysmorphism, and visceral and connective tissue abnormalities affecting the bones and vessels. The least severely affected individuals lack seizures, significant dysmorphism, and visceral involvement; they come to attention for neurologic signs and symptoms, including developmental delay with speech delay, strabismus, and/or ataxia. About half of patients have brain imaging anomalies, notably cerebral and cerebellar atrophy and thin corpus callosum, whereas the other half have normal brain imaging (summary by Liang et al., 2019).
Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures
MedGen UID:
1684879
Concept ID:
C5231486
Disease or Syndrome
Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (PAMDDFS) 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).
Intellectual developmental disorder 60 with seizures
MedGen UID:
1684702
Concept ID:
C5231497
Disease or Syndrome
Autosomal dominant intellectual developmental disorder-60 with seizures is characterized by global developmental delay apparent in infancy, followed by onset of seizures in the first years of life. Patients have delayed walking, an ataxic gait, and moderately to severely impaired intellectual development with poor speech (summary by Helbig et al., 2019).
Developmental and epileptic encephalopathy, 85, with or without midline brain defects
MedGen UID:
1708832
Concept ID:
C5393312
Disease or Syndrome
Developmental and epileptic encephalopathy-85 with or without midline brain defects (DEE85) is an X-linked neurologic disorder characterized by onset of severe refractory seizures in the first year of life, global developmental delay with impaired intellectual development and poor or absent speech, and dysmorphic facial features. The seizures tend to show a cyclic pattern with clustering. Many patients have midline brain defects on brain imaging, including thin corpus callosum and/or variable forms of holoprosencephaly (HPE). The severity and clinical manifestations are variable. Almost all reported patients are females with de novo mutations predicted to result in a loss of function (LOF). However, some patients may show skewed X inactivation, and the pathogenic mechanism may be due to a dominant-negative effect. The SMC1A protein is part of the multiprotein cohesin complex involved in chromatid cohesion during DNA replication and transcriptional regulation; DEE85 can thus be classified as a 'cohesinopathy' (summary by Symonds et al., 2017 and Kruszka et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Diets-Jongmans syndrome
MedGen UID:
1714920
Concept ID:
C5394263
Disease or Syndrome
Diets-Jongmans syndrome (DIJOS) is an autosomal dominant disorder characterized by mild to moderately impaired intellectual development with a recognizable facial gestalt (summary by Diets et al., 2019).
Neurodevelopmental disorder with hypotonia, microcephaly, and seizures
MedGen UID:
1710110
Concept ID:
C5394312
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, microcephaly, and seizures (NEDHYMS) is an autosomal recessive disorder characterized by global developmental delay with axial hypotonia, inability to sit or walk, and severely impaired intellectual development with absent language. Most patients develop early-onset intractable seizures that prevent normal development. Additional features include feeding difficulties with poor overall growth and microcephaly. Some patients may have spastic quadriplegia, poor eye contact due to cortical blindness, variable dysmorphic features, and nonspecific abnormalities on brain imaging (summary by Tan et al., 2020).
Nizon-Isidor syndrome
MedGen UID:
1715748
Concept ID:
C5394350
Disease or Syndrome
Nizon-Isidor syndrome (NIZIDS) is a neurodevelopmental disorder characterized by global developmental delay, mildly delayed walking, poor speech and language, variably impaired intellectual development, and behavioral abnormalities, such as autistic features or attention deficit-hyperactivity disorder (ADHD). Some patients may have additional features, including nonspecific facial dysmorphism, gastrointestinal difficulties, distal hand anomalies, and thin corpus callosum on brain imaging (summary by Nizon et al., 2019).
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures
MedGen UID:
1710849
Concept ID:
C5394372
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (NEDHCAS) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, delayed motor skills, and poor or absent speech. Most patients develop early-onset seizures and demonstrate cerebellar ataxia or dysmetria associated with progressive cerebellar atrophy on brain imaging. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis (summary by Nguyen et al., 2020). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome
MedGen UID:
1718475
Concept ID:
C5394523
Disease or Syndrome
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ACOGS) is a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, craniofacial dysmorphisms, and ocular, cardiac, and genital anomalies (Accogli et al., 2019).

Recent clinical studies

Etiology

Machol K, Rousseau J, Ehresmann S, Garcia T, Nguyen TTM, Spillmann RC, Sullivan JA, Shashi V, Jiang YH, Stong N, Fiala E, Willing M, Pfundt R, Kleefstra T, Cho MT, McLaughlin H, Rosello Piera M, Orellana C, Martínez F, Caro-Llopis A, Monfort S, Roscioli T, Nixon CY, Buckley MF, Turner A, Jones WD, van Hasselt PM, Hofstede FC, van Gassen KLI, Brooks AS, van Slegtenhorst MA, Lachlan K, Sebastian J, Madan-Khetarpal S, Sonal D, Sakkubai N, Thevenon J, Faivre L, Maurel A, Petrovski S, Krantz ID, Tarpinian JM, Rosenfeld JA, Lee BH; Undiagnosed Diseases Network., Campeau PM
Am J Hum Genet 2019 Jan 3;104(1):164-178. Epub 2018 Dec 20 doi: 10.1016/j.ajhg.2018.11.007. PMID: 30580808Free PMC Article
Wilson C, Playle R, Toma A, Zhurov A, Ness A, Richmond S
Am J Med Genet A 2013 Jan;161A(1):4-12. Epub 2012 Dec 3 doi: 10.1002/ajmg.a.35515. PMID: 23208817

Diagnosis

Blomqvist M, Smeland MF, Lindgren J, Sikora P, Riise Stensland HMF, Asin-Cayuela J
Cold Spring Harb Mol Case Stud 2019 Jun;5(3) Epub 2019 Jun 3 doi: 10.1101/mcs.a003954. PMID: 30886116Free PMC Article
Yamamoto T, Shimojima K, Yamazaki S, Ikeno K, Tohyama J
Congenit Anom (Kyoto) 2016 Nov;56(6):253-255. doi: 10.1111/cga.12172. PMID: 27230627
Kosho T
Pediatr Int 2016 Feb;58(2):88-99. doi: 10.1111/ped.12878. PMID: 26646600
Dikow N, Maas B, Gaspar H, Kreiss-Nachtsheim M, Engels H, Kuechler A, Garbes L, Netzer C, Neuhann TM, Koehler U, Casteels K, Devriendt K, Janssen JW, Jauch A, Hinderhofer K, Moog U
Am J Med Genet A 2013 Sep;161A(9):2158-66. Epub 2013 Aug 2 doi: 10.1002/ajmg.a.36046. PMID: 23913520
Bialer MG, Wilson WG, Kelly TE
Am J Med Genet 1989 Jul;33(3):314-7. doi: 10.1002/ajmg.1320330306. PMID: 2679089

Prognosis

Craddock KE, Okur V, Wilson A, Gerkes EH, Ramsey K, Heeley JM, Juusola J, Vitobello A, Dupeyron MB, Faivre L, Chung WK
Cold Spring Harb Mol Case Stud 2019 Aug;5(4) Epub 2019 Aug 1 doi: 10.1101/mcs.a004200. PMID: 31167805Free PMC Article
Hamilton MJ, Caswell RC, Canham N, Cole T, Firth HV, Foulds N, Heimdal K, Hobson E, Houge G, Joss S, Kumar D, Lampe AK, Maystadt I, McKay V, Metcalfe K, Newbury-Ecob R, Park SM, Robert L, Rustad CF, Wakeling E, Wilkie AOM, Study TDDD, Twigg SRF, Suri M
J Med Genet 2018 Jan;55(1):28-38. Epub 2017 Oct 11 doi: 10.1136/jmedgenet-2017-104620. PMID: 29021403Free PMC Article

Clinical prediction guides

Craddock KE, Okur V, Wilson A, Gerkes EH, Ramsey K, Heeley JM, Juusola J, Vitobello A, Dupeyron MB, Faivre L, Chung WK
Cold Spring Harb Mol Case Stud 2019 Aug;5(4) Epub 2019 Aug 1 doi: 10.1101/mcs.a004200. PMID: 31167805Free PMC Article
Hamilton MJ, Caswell RC, Canham N, Cole T, Firth HV, Foulds N, Heimdal K, Hobson E, Houge G, Joss S, Kumar D, Lampe AK, Maystadt I, McKay V, Metcalfe K, Newbury-Ecob R, Park SM, Robert L, Rustad CF, Wakeling E, Wilkie AOM, Study TDDD, Twigg SRF, Suri M
J Med Genet 2018 Jan;55(1):28-38. Epub 2017 Oct 11 doi: 10.1136/jmedgenet-2017-104620. PMID: 29021403Free PMC Article
Yamamoto T, Shimojima K, Yamazaki S, Ikeno K, Tohyama J
Congenit Anom (Kyoto) 2016 Nov;56(6):253-255. doi: 10.1111/cga.12172. PMID: 27230627

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