Cohen Syndrome

Excerpt

Clinical characteristics: Cohen syndrome is characterized by early-onset hypotonia, developmental delay, and moderate-to-profound intellectual disability; at least 20% of individuals are unable to communicate verbally. In infancy and childhood weight gain is poor due to feeding difficulties. However, in the early teen years rapid weight gain (without a change in appetite, food intake, or activity) leads to significant truncal obesity; short stature is common. Ophthalmologic findings include early childhood onset of progressive high myopia and retinal dystrophy. Mild-to-moderate neutropenia, present in almost all individuals, may be associated with recurrent infections and/or aphthous ulcers. Joint laxity can lead to kyphosis and scoliosis. Individuals with Cohen syndrome are described as having a cheerful and friendly disposition.

Diagnosis/testing: The diagnosis of Cohen syndrome is established in a proband with suggestive findings and biallelic pathogenic variants in VPS13B identified by molecular genetic testing.

Management: Treatment of manifestations: Early educational intervention and physical, occupational, and speech therapy to help address developmental delay and hypotonia; spectacle correction for refractive errors and low vision services for the visually impaired; treatment of recurrent infections per standard care (with caution regarding medications that could decrease neutrophil count); treatment of scoliosis and kyphosis by an experienced orthopedist.

Surveillance: Routing monitoring of growth and weight gain, developmental progress and educational needs, neurologic findings for emergence of new issues, ophthalmologic findings, possible emergence of scoliosis or kyphosis, and neutropenia and infection risk.

Genetic counseling: Cohen syndrome is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a VPS13B pathogenic variant, each sib of an affected individual has at conception 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. Once the VPS13B pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.