myopia

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

Gyrate Atrophy

Clinical Characteristics
Ocular Features: 

Gyrate atrophy is characterized by night blindness, myopia, and multiple round islands of peripheral chorioretinal degeneration which often appear in the first decade of life, sometimes as early as five years of age. Night blindness often begins in late childhood. The atrophic areas slowly progress to the posterior pole and may eventually affect central vision. Both eyes are usually symmetrically affected. All patients have myopia, some with refractive errors ranging up to -20 D. Fluorescein angiography shows hyperfluorescent at the edges of the peripheral atrophy. A zone of pigmentary changes can be seen between normal and atrophic areas.  The electroretinogram may show reduced rod and cone responses with rods affected more than cones in early phases. Dark-adapted ERG documents elevated rod thresholds.  Swollen mitochondria have been described in photoreceptors, corneal epithelium, and in the nonpigmented ciliary epithelium.  Elevated levels of ornithine are found in plasma, urine, spinal fluid and aqueous humor.  Macular edema is commonly present and posterior subcapsular cataracts requiring surgery are common.

Systemic Features: 

Mild muscle weakness may occur due to tubular aggregates in type 2 muscle fibers, which can be visualized with electron microscopy and may lead to loss of these fibers and muscle wasting. Fine, straight hairs have been observed with patches of alopecia. Slow wave background changes on EEG have been described in about one-third of patients and peripheral neuropathy is sometimes a feature.  Hearing loss has been described as well. Some newborns have a temporary elevation of plasma ammonia but once treated usually does not recur.

Genetics

Gyrate atrophy is an autosomal recessive disorder, caused by mutations in the OAT (ornithine aminotransferase) gene on chromosome 10 (10q26).  The enzyme is part of a nuclear-encoded mitochondrial matrix complex.  Many allelic variants have been found.  A large number of affected patients of Finnish origin, most of who share the common L402P mutation, have been described.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

A low protein and especially an arginine-restricted diet have been shown to slow loss of function as measured by ERG and visual field changes.
 

References
Article Title: 

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