VPS13B-related Cohen Syndrome with GDD, microcephaly, absent speech and ASD

Moosa, S. (2025). VPS13B-related Cohen Syndrome with GDD, microcephaly, absent speech and ASD (Version 1) [DataSet]. GestaltMatcher Database.

We describe a 4-year-old girl, born to healthy, non-consanguineous South African parents. She presents with autism spectrum disorder (ASD) level 3, severe global developmental delay, and intellectual disability. Dysmorphic features include bifrontal narrowing, low anterior hairline, and mild hypotelorism. Additional findings are symmetrical microcephaly, failure to thrive, and proportionate short stature. Notably, she has long eyelashes, does not display truncal obesity, and requires spectacles. She attends a special-needs crèche. Family history is unremarkable, with her older brother being healthy. The clinical presentation is consistent with Cohen syndrome (OMIM #216550). Whole-exome sequencing identified two compound heterozygous VPS13B (NM_017890.5) variants: c.2381del; p.(Pro794GlnfsTer33), classified as Pathogenic (PVS1, PM2, PP5), and c.6795C>A; p.(Tyr2265Ter), classified as Likely Pathogenic (PVS1, PM2) according to ACMG guidelines.