Cognitive impairment, and Hirsutism

Gingival fibromatosis - hypertrichosis syndrome is a rare autosomal dominant disorder characterized by a generalized enlargement of the gingiva occurring at birth or during childhood that is associated with generalized hypertrichosis developing at birth, during the first years of life, or at puberty and predominantly affecting the face, upper limbs, and midback.

GINGIVAL FIBROMATOSIS-HYPERTRICHOSIS SYNDROME Is also known as chromosome 17q24.2-q24.3 deletion syndrome|chromosome 17q24.2-q24.3 duplication syndrome|microdeletion 17q24.2-q24.3 syndrome|congenital generalized hypertrichosis terminalis|hirsutism-congenital gingival hyperplasia syndrome|microduplication 17q24.2-q24.

• Intellectual disability
• Seizures
• Hearing impairment
• Ataxia
• Abnormal facial shape

SOURCES: ORPHANET MESH OMIM MENDELIAN

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011).For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (OMIM ).

CEREBELLAR ATAXIA, MENTAL RETARDATION, AND DYSEQUILIBRIUM SYNDROME 2; CAMRQ2 Is also known as cerebellar ataxia and mental retardation with or without quadrupedal locomotion 2

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Ataxia

SOURCES: MESH OMIM MENDELIAN

Severe neurodegenerative syndrome with lipodystrophy is a rare, genetic, neurodegenerative disorder characterized by progressive psychomotor and cognitive regression (manifesting with gait ataxia, spasticity, loss of language, mild to severe intellectual disability, pyramidal and extrapyramidal signs and, frequently, development of tretraplegia or tetraparesis) associated with variable degrees of lipodystrophy, hepatomegaly, hypertriglyceridemia and muscular hypertorphy. Hyperactivity, tremor and development of seizures may also be associated.

SEVERE NEURODEGENERATIVE SYNDROME WITH LIPODYSTROPHY Is also known as severe neurodegenerative syndrome due to bscl2 deficiency

• Seizures
• Global developmental delay
• Ataxia
• Spasticity
• Cognitive impairment

SOURCES: OMIM ORPHANET MENDELIAN

Neurocutaneous melanocytosis (NCM) is a rare congenital neurological disorder characterized by abnormal aggregations of nevomelanocytes within the central nervous system (leptomeningeal melanocytosis) associated with large or giant congenital melanocytic nevi (CMN; see this term). NCM can be asymptomatic or present as variably severe and progressive neurological impairment, sometimes resulting in death.

NEUROCUTANEOUS MELANOCYTOSIS Is also known as neurocutaneous melanosis|neuromelanosis|ncm

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: MESH OMIM ORPHANET MENDELIAN

Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes (Garg, 2004).For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (OMIM ).

LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 2; CGL2 Is also known as berardinelli-seip congenital lipodystrophy, type 2|brunzell syndrome, bscl2-related|lipoatrophic diabetes, congenital|seip syndrome|lipodystrophy, total, and acromegaloid gigantism|lipodystrophy, berardinelli-seip congenital, type 2|berardinelli syndrome

• Intellectual disability
• Cognitive impairment
• Hypertension
• Hepatomegaly
• Cardiomyopathy

SOURCES: OMIM MENDELIAN

Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomaly syndrome characterized by mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The classic facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose with the nasal septum, highly arched palate, mild micrognathia, and characteristic grimacing or abnormal smile (Rubinstein and Taybi, 1963; review by Hennekam, 2006).About 50 to 70% of patients have RSTS1 due to mutation in the CREBBP gene (OMIM ). RSTS2 is much less common, and about 3% of patients have mutations in the EP300 gene. RSTS2 appears to be associated with a milder phenotype than RSTS1. Patients with RSTS2 have less severe facial dysmorphism and better cognitive function, but may have more severe microcephaly and malformation of facial bone structures compared to those with RSTS1 (Bartsch et al., 2010).For a discussion of genetic heterogeneity of Rubinstein-Taybi syndrome, see RSTS1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Short stature
• Microcephaly
• Scoliosis

SOURCES: ORPHANET OMIM MENDELIAN

Spondyloepimetaphyseal dysplasia, Geneviève type is a rare primary bone dysplasia characterized by severe developmental delay and skeletal dysplasia (including short stature, premature carpal ossification, platyspondyly, longitudinal metaphyseal striations, and small epiphyses), as well as moderate to severe intellectual disability and facial dysmorphism, including prominent forehead, mild synophrys, depressed nasal bridge, prominent bulbous nasal tip and full lips.

SPONDYLOEPIMETAPHYSEAL DYSPLASIA, GENEVIÈVE TYPE Is also known as nans deficiency|semd, genevieve type|semdg|semd, geneviÈve type

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM ORPHANET MESH MENDELIAN

The Sanfilippo syndrome, or mucopolysaccharidosis III, is an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate (Esposito et al., 2000). The disorder is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. Type A has been reported (van de Kamp et al., 1981) to be the most severe, with earlier onset and rapid progression of symptoms and shorter survival. Genetic Heterogeneity of Mucopolysaccharidosis Type IIIMPS III includes 4 types, each due to the deficiency of a different enzyme: heparan N-sulfatase (type A); alpha-N-acetylglucosaminidase (type B; {252920}); acetyl CoA:alpha-glucosaminide acetyltransferase (type C; {252930}); and N-acetylglucosamine 6-sulfatase (type D; {252940}).

MUCOPOLYSACCHARIDOSIS, TYPE IIIA; MPS3A Is also known as mps iiia|sulfamidase deficiency|sanfilippo syndrome a|heparan sulfate sulfatase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia

SOURCES: OMIM MENDELIAN

Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.

SIALURIA Is also known as sialuria, french type

• Seizures
• Global developmental delay
• Generalized hypotonia
• Scoliosis
• Hypertelorism

SOURCES: ORPHANET OMIM MENDELIAN

Cornelia de Lange syndrome is a multisystem developmental disorder characterized by distinctive facial dysmorphism, pre- and postnatal growth failure, delayed psychomotor development and intellectual disability, hypertrichosis, and sometimes distal limb malformations (summary by Gil-Rodriguez et al., 2015).For a phenotypic description and a discussion of genetic heterogeneity of Cornelia de Lange syndrome, see {122470}.

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN