Clinical characteristics: Cohen syndrome is characterized by failure to thrive in infancy and childhood; truncal obesity in the teen years; early-onset hypotonia and developmental delays; microcephaly developing during the first year of life; moderate to profound psychomotor retardation; progressive retinochoroidal dystrophy and high myopia; neutropenia in many with recurrent infections and aphthous ulcers in some; a cheerful disposition; joint hypermobility; and characteristic facial features.
Diagnosis/testing: The diagnosis of Cohen syndrome is based on clinical findings, but no consensus diagnostic criteria exist. Identification of biallelic pathogenic variants in VPS13B (also known as COH1) on molecular genetic testing establishes the diagnosis if clinical features are inconclusive.
Management: Treatment of manifestations: Spectacle correction of refractive errors, low-vision training for the visually impaired, and psychosocial support. Early intervention and physical, occupational, and speech therapy help address developmental delay, hypotonia, joint hyperextensibility, and motor clumsiness. Recurrent infections are treated per standard therapy; consideration should be given to use of granulocyte-colony stimulating factor (G-CSF) for the treatment of neutropenia.
Surveillance: Annual ophthalmologic and hematologic evaluations; monitor growth and weight gain.
Agents/circumstances to avoid: Caution should be used regarding medications with the potential to decrease the neutrophil count.
Genetic counseling: Cohen syndrome is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Offspring of an individual with Cohen syndrome are obligate heterozygotes (carriers). Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants have been identified in an affected family member.
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