Cohen syndrome: further delineation and inheritance

Area of Science:

• Medical Genetics
• Pediatrics

Background:

• Cohen syndrome is a rare genetic disorder characterized by distinctive facial features, developmental delays, and skeletal abnormalities.
• Understanding the inheritance patterns and clinical variability is crucial for diagnosis and management.

Observation:

• A sibship of four individuals (2 male, 2 female) presented with Cohen syndrome.
• Common manifestations included moderate intellectual disability, microcephaly, hypotonia, and specific limb characteristics (narrow hands/feet, elongated digits).
• Facial features like exotropia, prominent ears, short philtrum, and high nasal bridge were observed with varying severity.

Findings:

• Three sibs exhibited short stature (2.0-3.5 SD below mean), truncal obesity, and mild pubertal delay.
• One individual also presented with rheumatoid arthritis.
• Normal chromosomes and the absence of endocrine issues were noted, supporting autosomal recessive inheritance.
• Reproductive capacity was demonstrated, with one affected individual having an unaffected child with normal development.

Implications:

• The findings reinforce the hypothesis of autosomal recessive inheritance for Cohen syndrome.
• Microcephaly and short stature are significant indicators of the syndrome.
• Variable expressivity, even within families, may lead to underdiagnosis of milder cases, highlighting the need for comprehensive evaluation.