Intellectual disability, severe, and Synophrys

Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome is a rare, syndromic intellectual disability primarily characterized by moderate to severe intellectual disability, true-to-relative microcephaly and brain abnormalities including a thin corpus callosum, cerebellar hypoplasia, cerebral white matter hypoplasia and multi-focal hyperintensity of cerebral white matter on MRI. Obesity and distinctive craniofacial dysmorphism (including brachycephaly, round face, straight eyebrows, synophrys, hypertelorism, epicanthus, wide and depressed nasal bridge, protruding ears with uplifted lobe, downslanting corners of the mouth) are additional features.

INTELLECTUAL DISABILITY-OBESITY-BRAIN MALFORMATIONS-FACIAL DYSMORPHISM SYNDROME Is also known as autosomal recessive intellectual disability due to trappc9 deficiency

• Seizures
• Global developmental delay
• Microcephaly
• Hypertelorism
• Abnormal facial shape

SOURCES: ORPHANET MENDELIAN

1q44 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, developmental delay, in particular of expressive speech, seizures and hypotonia.

1Q44 MICRODELETION SYNDROME Is also known as del(1)(q44)|monosomy 1q44

• Global developmental delay
• Short stature
• Microcephaly
• Scoliosis
• Growth delay

SOURCES: ORPHANET 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

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

SOURCES: MESH OMIM MENDELIAN

Holoprosencephaly associated with mutations in the ZIC2 gene.

• Intellectual disability
• Global developmental delay
• Microcephaly
• Hypertelorism
• Abnormal facial shape

SOURCES: OMIM MESH MENDELIAN

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

SOURCES: OMIM MESH MENDELIAN

Corpus callosum agenesis-abnormal genitalia syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by agenesis of the corpus callosum, mild to severe neurological manifestations (intellectual disability, developmental delay, epilepsy, dystonia), and urogenital anomalies (hypospadias, cryptorchidism, renal dysplasia, ambiguous genitalia). Additionally, skeletal anomalies (limb contractures, scoliosis), dysmorphic facial features (prominent supraorbital ridges, synophris, large eyes) and optic atrophy have been observed.

CORPUS CALLOSUM AGENESIS-ABNORMAL GENITALIA SYNDROME Is also known as proud syndrome|microcephaly-corpus callosum agenesis-abnormal genitalia syndrome|acc with abnormal genitalia|acc-abnormal genitalia syndrome|proud-levine-carpenter syndrome

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

SOURCES: MESH 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

Waardenburg syndrome type 3 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; presence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi; and upper limb abnormalities (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 3 is also referred to as 'Klein-Waardenburg syndrome' (Gorlin et al., 1976). Clinical Variability of Waardenburg Syndrome Types 1-4Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1 ) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type IV (WS4 ), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010).

WAARDENBURG SYNDROME, TYPE 3; WS3 Is also known as klein-waardenburg syndrome|waardenburg syndrome, type iii|waardenburg syndrome with upper limb anomalies

• Intellectual disability
• Generalized hypotonia
• Hearing impairment
• Microcephaly
• Hypertelorism

SOURCES: OMIM MENDELIAN

15q13.3 microdeletion (microdel15q13.3) syndrome is characterized by a wide spectrum of neurodevelopmental disorders with no or subtle dysmorphic features.

15Q13.3 MICRODELETION SYNDROME Is also known as del(15)(q13.3)|chromosome 15q13.3 microdeletion syndrome|monosomy 15q13.3

• Seizures
• Schizophrenia
• Bipolar affective disorder

SOURCES: MESH MENDELIAN