Isolated Pierre-Robin syndrome- MedGen UID:
- 19310
- •Concept ID:
- C0031900
- •
- Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulties during the neonatal period (summary by Tan et al., 2013).
Velocardiofacial syndrome- MedGen UID:
- 65085
- •Concept ID:
- C0220704
- •
- Disease or Syndrome
Individuals with 22q11.2 deletion syndrome (22q11.2DS) can present with a wide range of features that are highly variable, even within families. The major clinical manifestations of 22q11.2DS include congenital heart disease, particularly conotruncal malformations (ventricular septal defect, tetralogy of Fallot, interrupted aortic arch, and truncus arteriosus), palatal abnormalities (velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate), immune deficiency, characteristic facial features, and learning difficulties. Hearing loss can be sensorineural and/or conductive. Laryngotracheoesophageal, gastrointestinal, ophthalmologic, central nervous system, skeletal, and genitourinary anomalies also occur. Psychiatric illness and autoimmune disorders are more common in individuals with 22q11.2DS.
Marshall syndrome- MedGen UID:
- 82694
- •Concept ID:
- C0265235
- •
- Disease or Syndrome
Marshall syndrome (MRSHS) is characterized by midfacial hypoplasia, cleft palate, ocular anomalies including high myopia and cataracts, sensorineural hearing loss, short stature with spondyloepiphyseal dysplasia, and arthropathy. In contrast to Stickler syndrome type II, it has less severe eye findings but striking ocular hypertelorism, more pronounced maxillary hypoplasia, and ectodermal abnormalities (summary by Shanske et al., 1997 and Ala-Kokko and Shanske, 2009).
Cerebro-costo-mandibular syndrome- MedGen UID:
- 120537
- •Concept ID:
- C0265342
- •
- Disease or Syndrome
Cerebrocostomandibular syndrome (CCMS) is a rare autosomal dominant disorder characterized by branchial arch-derivative and thoracic malformations. A key craniofacial characteristic is micrognathia, often associated with cleft palate and feeding and airway difficulties. Patients with CCMS have a narrow chest and striking posterior rib gaps which distinguish this condition (summary by Tooley et al., 2016).
See CDG2G (611209) for a cerebrocostomandibular-like syndrome.
Osteopathia striata with cranial sclerosis- MedGen UID:
- 96590
- •Concept ID:
- C0432268
- •
- Disease or Syndrome
Most females with osteopathia striata with cranial sclerosis (OS-CS) present with macrocephaly and characteristic facial features (frontal bossing, hypertelorism, epicanthal folds, depressed nasal bridge, and prominent jaw). Approximately half have associated features including orofacial clefting and hearing loss, and a minority have some degree of developmental delay (usually mild). Radiographic findings of cranial sclerosis, sclerosis of long bones, and metaphyseal striations (in combination with macrocephaly) can be considered pathognomonic. Males can present with a mild or severe phenotype. Mildly affected males have clinical features similar to affected females, including macrocephaly, characteristic facial features, orofacial clefting, hearing loss, and mild-to-moderate learning delays. Mildly affected males are more likely than females to have congenital or musculoskeletal anomalies. Radiographic findings include cranial sclerosis and sclerosis of the long bones; Metaphyseal striations are more common in males who are mosaic for an AMER1 pathogenic variant. The severe phenotype manifests in males as a multiple-malformation syndrome, lethal in mid-to-late gestation, or in the neonatal period. Congenital malformations include skeletal defects (e.g., polysyndactyly, absent or hypoplastic fibulae), congenital heart disease, and brain, genitourinary, and gastrointestinal anomalies. Macrocephaly is not always present and longitudinal metaphyseal striations have not been observed in severely affected males, except for those who are mosaic for the AMER1 pathogenic variant.
Toriello-Carey syndrome- MedGen UID:
- 163225
- •Concept ID:
- C0796184
- •
- Disease or Syndrome
Toriello-Carey syndrome is a multiple congenital anomaly disorder with variable systemic manifestations, most commonly including mental retardation, agenesis of the corpus callosum, postnatal growth delay, cardiac defects, usually septal defects, distal limb defects, and urogenital anomalies in affected males. Patients have facial dysmorphic features, micrognathia, including full cheeks, hypertelorism, flattened nasal bridge, anteverted nares, and short neck. Not all features are found in all patients and some patients may have additional features such as anal anomalies or hernias (summary by Toriello et al., 2003).
In a review of the Toriello-Carey syndrome, Toriello et al. (2016) stated that while corpus callosum abnormalities and micrognathia with highly arched or cleft palate are seen in most patients, other manifestations are widely variable. They noted that etiologic heterogeneity has been observed in reported patients, with at least 20% of patients having chromosome anomalies, and that no good candidate genes have been identified by exome sequencing. The authors commented that this condition might not be a unitary diagnostic entity. They recommended chromosome microarray for any child suspected of having the condition, followed by standard of care by genetic testing.
Intellectual disability-brachydactyly-Pierre Robin syndrome- MedGen UID:
- 325196
- •Concept ID:
- C1837564
- •
- Disease or Syndrome
Intellectual disability-brachydactyly-Pierre Robin syndrome is a rare developmental defect during embryogenesis syndrome characterized by mild to moderate intellectual disability and phsychomotor delay, Robin sequence (incl. severe micrognathia and soft palate cleft) and distinct dysmorphic facial features (e.g. synophris, short palpebral fissures, hypertelorism, small, low-set, and posteriorly angulated ears, bulbous nose, long/flat philtrum, and bow-shaped upper lip). Skeletal anomalies, such as brachydactyly, clinodactyly, small hands and feet, and oral manifestations (e.g. bifid, short tongue, oligodontia) are also associated. Additional features reported include microcephaly, capillary hemangiomas on face and scalp, ventricular septal defect, corneal clouding, nystagmus and profound sensorineural deafness.
Catel-Manzke syndrome- MedGen UID:
- 375536
- •Concept ID:
- C1844887
- •
- Disease or Syndrome
Catel-Manzke syndrome is characterized by the Pierre Robin anomaly, which comprises cleft palate, glossoptosis, and micrognathia, and a unique form of bilateral hyperphalangy in which there is an accessory bone inserted between the second metacarpal and its corresponding proximal phalanx, resulting in radial deviation of the index finger (summary by Manzke et al., 2008).
Otospondylomegaepiphyseal dysplasia, autosomal dominant- MedGen UID:
- 341234
- •Concept ID:
- C1848488
- •
- Disease or Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Richieri Costa-Pereira syndrome- MedGen UID:
- 336581
- •Concept ID:
- C1849348
- •
- Disease or Syndrome
Patients with Richieri-Costa-Pereira syndrome display a pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of the mandible, cleft palate/Robin sequence, absence of lower central incisors, minor ear anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability is also a common finding (summary by Favaro et al., 2011).
Stickler syndrome type 2- MedGen UID:
- 347615
- •Concept ID:
- C1858084
- •
- Disease or Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Arthrogryposis multiplex congenita-whistling face syndrome- MedGen UID:
- 349231
- •Concept ID:
- C1859711
- •
- Disease or Syndrome
An extremely rare type of arthrogryposis multiplex congenita with the combination of multiple joint contractures with movement limitation and microstomia with a whistling appearance of the mouth that may cause feeding, swallowing and speech difficulties, a distinctive expressionless facies, severe developmental delay, central and autonomous nervous system dysfunction, occasionally Pierre-Robin sequence and lethality generally occurring during the first months of life.
Ventricular extrasystoles with syncopal episodes-perodactyly-robin sequence syndrome- MedGen UID:
- 395493
- •Concept ID:
- C1860471
- •
- Disease or Syndrome
This syndrome is characterized by cardiac arrhythmias (ventricular extrasystoles manifesting as bigeminy or multifocal tachycardia with syncopal episodes), perodactyly (hypoplasia and/or agenesis of the distal phalanges of the toes) and Pierre-Robin sequence (see this term).
Pierre Robin sequence with pectus excavatum and rib and scapular anomalies- MedGen UID:
- 355549
- •Concept ID:
- C1865783
- •
- Disease or Syndrome
Robin sequence-oligodactyly syndrome- MedGen UID:
- 358176
- •Concept ID:
- C1868309
- •
- Disease or Syndrome
Robin sequence-oligodactyly syndrome is a rare, genetic, developmental defect during embryogenesis syndrome characterized by Robin sequence (i.e. severe micrognathia, retroglossia and U-shaped cleft of the posterior palate) associated with pre- and postaxial oligodactyly. Facial features can include a narrow face and narrow lower dental arch. Clinodactyly, absent phalanx, metacarpal fusions, and hypoplastic carpals have also been reported. There have been no further descriptions in the literature since 1986.
Stickler syndrome type 1- MedGen UID:
- 810955
- •Concept ID:
- C2020284
- •
- Disease or Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Chromosome 2q32-q33 deletion syndrome- MedGen UID:
- 436765
- •Concept ID:
- C2676739
- •
- Disease or Syndrome
SATB2-associated syndrome (SAS) is a multisystem disorder characterized by significant neurodevelopmental compromise with limited to absent speech, behavioral issues, and craniofacial anomalies. All individuals described to date have manifest developmental delay / intellectual disability, with severe speech delay. Affected individuals often have hypotonia and feeding difficulties in infancy. Behavioral issues may include autistic features, hyperactivity, and aggressiveness. Craniofacial anomalies may include palatal abnormalities (cleft palate, high-arched palate, and bifid uvula), micrognathia, and abnormal shape or size of the upper central incisors. Less common features include skeletal anomalies (osteopenia, pectus deformities, kyphosis/lordosis, and scoliosis), growth restriction, strabismus/refractive errors, congenital heart defects, genitourinary anomalies, and epilepsy. While dysmorphic features have been described in individuals with this condition, these features are not typically distinctive enough to allow for a clinical diagnosis of SAS.
Stevenson-Carey syndrome- MedGen UID:
- 383183
- •Concept ID:
- C2677763
- •
- Disease or Syndrome
Spondyloepiphyseal dysplasia congenita- MedGen UID:
- 412530
- •Concept ID:
- C2745959
- •
- Congenital Abnormality
Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Skeletal features are manifested at birth and evolve with time. Other features include myopia and/or retinal degeneration with retinal detachment and cleft palate (summary by Anderson et al., 1990).
PGM1-congenital disorder of glycosylation- MedGen UID:
- 414536
- •Concept ID:
- C2752015
- •
- Disease or Syndrome
Congenital disorder of glycosylation type It (CDG1T) is an autosomal recessive disorder characterized by a wide range of clinical manifestations and severity. The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism (summary by Tegtmeyer et al., 2014).
For a discussion of the classification of CDGs, see CDG1A (212065).
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.
Pierre Robin syndrome-faciodigital anomaly syndrome- MedGen UID:
- 443969
- •Concept ID:
- C2931064
- •
- Disease or Syndrome
The association of Pierre Robin sequence (retrognathia, cleft palate and glossoptosis), facial dysmorphism (high forehead with frontal bossing) and digital anomalies (tapering fingers, hyper convex nails, clinodactyly of the fifth fingers and short distal phalanges, finger-like thumbs and easily subluxated first metacarpophalangeal joints). Growth and mental development are normal. It has been described in two half brothers born to the same mother. Transmission appears to be X-linked recessive.
Chromosome 16p12.2-p11.2 deletion syndrome- MedGen UID:
- 462208
- •Concept ID:
- C3150858
- •
- Disease or Syndrome
The chromosome 16p12.2-p11.2 deletion syndrome is characterized phenotypically by dysmorphic facial features, feeding difficulties, recurrent ear infections, developmental delay, and cognitive impairment. Additional features, such as heart defects and short stature, are variable (Ballif et al., 2007; Battaglia et al., 2009).
The pericentric region of chromosome 16, specifically involving 16p12-p11, is a structurally complex region enriched in repetitive sequence elements, rendering this region susceptible to deletion or rearrangement (Ballif et al., 2007). There are several phenotypes associated with variation in this region: see 611913 for a deletion or duplication at 16p11.2 associated with autism; see 136570 for discussion of a recurrent 520-kb deletion at 16p12.1 associated with developmental delay and craniofacial dysmorphism; and see 613444 for a 220-kb deletion at 16p11.2 associated with isolated severe early-onset obesity and obesity with developmental delay.
Battaglia et al. (2009) emphasized that the region at chromosome 16p11.2 that confers susceptibility to autism (AUTS14; see 611913) is located more centromeric to and is distinct from the 16p12.2-p11.2 region involved in the multiple congenital anomalies and intellectual disability phenotype.
Multiple congenital anomalies-hypotonia-seizures syndrome 2- MedGen UID:
- 477139
- •Concept ID:
- C3275508
- •
- Disease or Syndrome
Multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2) is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, early-onset myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability; these features are consistent with a form of developmental and epileptic encephalopathy (DEE) (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.
For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080).
For a discussion of nomenclature and genetic heterogeneity of DEE, see 308350.
For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Stickler syndrome, type 5- MedGen UID:
- 481972
- •Concept ID:
- C3280342
- •
- Disease or Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Periventricular nodular heterotopia 7- MedGen UID:
- 934636
- •Concept ID:
- C4310669
- •
- Disease or Syndrome
Periventricular nodular heterotopia-7 (PVNH7) is a neurologic disorder characterized by abnormal neuronal migration during brain development resulting in delayed psychomotor development and intellectual disability; some patients develop seizures. Other features include cleft palate and 2-3 toe syndactyly (summary by Broix et al., 2016).
For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see 300049.
Frontometaphyseal dysplasia 2- MedGen UID:
- 934664
- •Concept ID:
- C4310697
- •
- Disease or Syndrome
Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia characterized by supraorbital hyperostosis, undermodeling of the small bones, and small and large joint contractures, as well as extraskeletal developmental abnormalities, primarily of the cardiorespiratory system and genitourinary tract. Patients with FMD2 appear to have a propensity for keloid formation (summary by Wade et al., 2016).
For a discussion of genetic heterogeneity of frontometaphyseal dysplasia, see FMD1 (305620).
Gabriele de Vries syndrome- MedGen UID:
- 1375401
- •Concept ID:
- C4479652
- •
- Disease or Syndrome
Gabriele-de Vries syndrome is characterized by mild-to-profound developmental delay / intellectual disability (DD/ID) in all affected individuals and a wide spectrum of functional and morphologic abnormalities. Intrauterine growth restriction or low birth weight and feeding difficulties are common. Congenital brain, eye, heart, kidney, genital, and/or skeletal system anomalies have also been reported. About half of affected individuals have neurologic manifestations, including hypotonia and gait abnormalities. Behavioral issues can include attention-deficit/hyperactivity disorder, anxiety, autism or autistic behavior, and schizoaffective disorder.
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis- MedGen UID:
- 1676818
- •Concept ID:
- C5193055
- •
- Disease or Syndrome
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis (SSASKS)is characterized by disproportionate short stature, defective tooth enamel formation, and skeletal dysplasia with severe scoliosis in some patients. Variable features include facial dysmorphism, moderate hearing impairment, and mildly impaired intellectual development (Ashikov et al., 2018).
Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome- MedGen UID:
- 1679105
- •Concept ID:
- C5193066
- •
- Disease or Syndrome
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by variable intellectual disability and/or developmental delay, epilepsy, generalized hypertrichosis, severe gingival overgrowth and visual impairment in some patients. Common craniofacial features include bitemporal narrowing, bushy and straight eyebrows, long eyelashes, low-set ears, deep/short philtrum, everted upper lip, prominent upper and lower vermilion, wide mouth, micrognathia, and retrognathia.
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1- MedGen UID:
- 1778119
- •Concept ID:
- C5542952
- •
- Disease or Syndrome
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2- MedGen UID:
- 1782253
- •Concept ID:
- C5543057
- •
- Disease or Syndrome
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies-2 (SSFSC2) is characterized by thin and short long bones, distinctive facial dysmorphism, and dental and skeletal abnormalities, in the absence of developmental delay or intellectual disability. Cardiac anomalies have been reported in some patients (Lin et al., 2021).
For a discussion of genetic heterogeneity of SSFSC, see SSFSC1 (617877).
Otospondylomegaepiphyseal dysplasia, autosomal recessive- MedGen UID:
- 1790497
- •Concept ID:
- C5551484
- •
- Disease or Syndrome
Otospondylomegaepiphyseal dysplasia (OSMED) is characterized by sensorineural hearing loss, enlarged epiphyses, disproportionate shortness of the limbs, abnormalities in vertebral bodies, and typical facial features (summary by Harel et al., 2005).
Chopra-Amiel-Gordon syndrome- MedGen UID:
- 1794185
- •Concept ID:
- C5561975
- •
- Disease or Syndrome
Chopra-Amiel-Gordon syndrome (CAGS) is an autosomal dominant disorder characterized by developmental delay and/or impaired intellectual development, speech delay, facial dysmorphism, and variable other features, including recurrent bacterial infections, ophthalmologic abnormalities, and nonspecific brain abnormalities (Chopra et al., 2021).
Carey-Fineman-Ziter syndrome 1- MedGen UID:
- 1804638
- •Concept ID:
- C5676876
- •
- Disease or Syndrome
Carey-Fineman-Ziter syndrome-1 (CFZS1) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. More variable features include dysmorphic facial features, brain abnormalities, and intellectual disability. It has been postulated that many clinical features in CFZS1 may be secondary effects of muscle weakness during development or brainstem anomalies (summary by Pasetti et al., 2016).
Di Gioia et al. (2017) determined that CFZS1 represents a slowly progressive congenital myopathy resulting from a defect in myoblast fusion.
Genetic Heterogeneity of Carey-Fineman-Ziter Syndrome
Carey-Fineman-Ziter syndrome-2 (CFZS2) is caused by mutation in the MYMX gene (619912) on chromosome 6p21.
Braddock-carey syndrome 1- MedGen UID:
- 1823961
- •Concept ID:
- C5774188
- •
- Disease or Syndrome
Braddock-Carey syndrome (BRDCS) is characterized by Pierre-Robin sequence, persistent congenital thrombocytopenia, agenesis of the corpus callosum, severe developmental delay, microcephaly, high forehead, sparse curly hair, downslanting palpebral fissures, telecanthus, inverted U-shaped upper vermilion, enamel hypoplasia, large posteriorly rotated ears, clinodactyly, and camptodactyly (Braddock et al., 2016).
Genetic Heterogeneity of Braddock-Carey Syndrome
BRDCS2 (619981) is caused by mutation in the KIF15 gene (617569) on chromosome 3p21.
Braddock-carey syndrome 2- MedGen UID:
- 1823962
- •Concept ID:
- C5774189
- •
- Disease or Syndrome
Braddock-Carey syndrome-2 (BRDCS2) is characterized by congenital thrombocytopenia, microcephaly, and facial dysmorphisms including Pierre-Robin sequence (Sleiman et al., 2017).
For a general phenotypic description and discussion of genetic heterogeneity of Braddock-Carey syndrom, see BRCDS1 (619980).
Microcephaly 30, primary, autosomal recessive- MedGen UID:
- 1824053
- •Concept ID:
- C5774280
- •
- Disease or Syndrome
Autosomal recessive primary microcephaly-30 (MCPH30) is characterized by small head circumference, poor overall growth, and global developmental delay with variably impaired intellectual development. Affected individuals have been reported to have variable additional congenital anomalies, including atrial septal defect, dysmorphic facial features, tracheal stenosis, and anomalies of the skin and teeth (Carvalhal et al., 2022).
For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Leukodystrophy, hypomyelinating, 26, with chondrodysplasia- MedGen UID:
- 1840948
- •Concept ID:
- C5830312
- •
- Disease or Syndrome
Hypomyelinating leukodystrophy-26 with chondrodysplasia (HLD26) is characterized by severe psychomotor delay, predominantly involving motor and expressive language development, with cerebral and cerebellar atrophy and corpus callosum hypoplasia. In addition, patients show pre- and postnatal growth retardation, early-onset scoliosis, and dislocations of large joints (Guasto et al., 2022).
For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see HLD1 (312080).