Three Siblings with Cohen Syndrome and a Novel Vacuolar Protein Sorting 13 Homolog B Mutation

Abstract

Background: Cohen syndrome (CS) is caused by an autosomal recessive (AR) mutation of the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. It is characterized by hypotonia, obesity, prominent incisors, and mental retardation. It is diagnosed by the satisfaction of various systems of clinical diagnostic criteria. Molecular confirmation is by clinical exome sequencing. Clinical Description: We reported three siblings from a Kashmiri family with a positive history of consanguinity. The index case, a 26-month-old boy, was diagnosed with neutropenia during the workup for recurrent respiratory infections. He was also noted to have developmental delay, short stature, obesity, microcephaly, and facial dysmorphism. Retinitis pigmentosa was found. The diagnosis of CS was established on the detection of a pathogenic novel homozygous frameshift variant in the VPS13B gene. Evaluation of the family identified two other siblings, an 11-year-old boy and a 9-year-old girl, who satisfied the clinical criteria. Management and Outcome: The parents underwent genetic counseling. The affected children are under follow-up by a multidisciplinary team with regular monitoring of various parameters as per standard recommendations. Conclusion: Pediatricians should consider the application of diagnostic criteria of CS in a child with neutropenia, short stature, developmental delay, and microcephaly, if there is a setting of consanguinity. The diagnosis should be confirmed by genetic testing.

Keywords

• developmental delay
• dysmorphism
• hypotonia
• microcephaly
• retinopathy