OMIM ID:
Cohen Syndrome
Alternate Names
Defective Genes
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
Inheritance
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
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.