obesity

Cohen Syndrome

Clinical Characteristics
Ocular Features: 

Patients have early onset night blindness with defective dark adaptation and corresponding ERG abnormalities.  Visual fields are constricted peripherally and central visual acuity is variably reduced.  A pigmentary retinopathy is often associated with a bull’s eye maculopathy. The retinopathy is progressive as is high myopia.  The eyebrows and eyelashes are long and thick and the eyelids are highly arched and often ‘wave-shaped’.  Congenital ptosis, optic atrophy, and ectopia lentis have also been reported.

Systemic Features: 

Affected individuals have a characteristic facial dysmorphism in which ocular features play a role.  They have a low hairline, a prominent nasal root, and a short philtrum.  The tip of the nose appears bulbous. The head circumference is usually normal at birth but lags behind in growth so that older individuals appear microcephalic.  Delays in developmental milestones are noticeable in the first year of life.  Mild to moderate mental retardation is characteristic but does not progress.  Hypotonia is common early, and many individuals are short in stature.  Low white counts and frank neutropenia are often seen and some patients have frequent infections, especially of the oral mucosa and the respiratory tract.  A cheerful disposition is said to be characteristic.

Genetics

This is an autosomal recessive disorder caused by a mutation in the COH1 (VPS13B) gene on chromosome 8 (8q22-q23).  However, a variety of mutations have been reported including deletions and missense substitutions and, since these are scattered throughout the gene, complete sequencing is necessary before a negative result can be confirmed.

There is evidence of significant clinical heterogeneity between cohorts descended from different founder mutations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Corrective lenses for myopia can be helpful.  For patients with sufficient vision, low vision aids can be helpful.  Selected individuals may benefit from vocational and speech therapy.  Infections should be treated promptly.

References
Article Title: 

Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport

Kolehmainen J, Black GC, Saarinen A, Chandler K, Clayton-Smith J, Traskelin AL, Perveen R, Kivitie-Kallio S, Norio R, Warburg M, Fryns JP, de la Chapelle A, Lehesjoki AE. Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport. Am J Hum Genet. 2003 Jun;72(6):1359-69.

PubMed ID: 
12730828

Biemond Syndrome II

Clinical Characteristics
Ocular Features: 

This disorder may belong to the spectrum of Bardet-Biedl syndromes (209900) but is listed separately because of the prominent association of iris colobomata.  Retinal dystrophy resembling retinitis pigmentosa is also part of this disorder but the rarity of cases precludes a full description of the phenotype.

Systemic Features: 

Underdevelopment of the external genitalia is more prominent in males.  Obesity, hydrocephalus and mental retardation are also features.  Postaxial polydactyly is common.  Renal disease does not seem to be part of this disorder.

Genetics

Little is known about the inheritance or genetic defect responsible.  Colobomas and polydactyly have been found in relatives of patients with Biemond syndrome suggesting that this may be an autosomal dominant disorder with variable penetrance.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

None known.

References
Article Title: 

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