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 [1]) 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.

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: report of nine cases and review of the literature, with emphasis on ophthalmic features. [2]

Taban M, Memoracion-Peralta DS, Wang H, Al-Gazali LI, Traboulsi EI. Cohen syndrome: report of nine cases and review of the literature, with emphasis on ophthalmic features. J AAPOS. 2007 Oct;11(5):431-7.

PubMed ID:

17383910

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 [3]

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

Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C) [4]

van de Kamp JJ, Niermeijer MF, von Figura K, Giesberts MA. Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C). Clin Genet. 1981 Aug;20(2):152-60.

PubMed ID:

6796310