Further evidence for a wide phenotypic and mutational spectrum of Cohen syndrome: case report and literature review

Cohen syndrome (CS) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the VPS13B gene. It is characterized by early-onset multisystemic symptoms, including chorioretinal dystrophy, progressive high myopia, developmental delay, hypotonia, abnormal fat distribution, short stature, microcephaly, facial dysmorphism, and leukopenia. However, the condition exhibits extensive phenotypic and allelic heterogeneity. Here, we report a 24-year-old male presenting with atypical retinitis pigmentosa, myopia, leukopenia, abnormal fat distribution, and minor facial dysmorphic features. The patient showed neither neurologic symptoms nor other commonly observed CS traits. Multigene next-generation sequencing (NGS) panel testing revealed two novel VPS13B variants - an intragenic deletion encompassing exon 5 and a donor splice site variant c.11392 + 2dup in a compound heterozygous state. Furthermore, we conducted a literature review and summarized the phenotypic and genetic heterogeneity of CS, with an additional emphasis on individuals exhibiting mild manifestations. The present study introduces two novel VPS13B variants associated with mild CS and highlights the possibility that biallelic VPS13B mutations may lead to a less severe clinical presentation without developmental delay, which is widely considered an inherent part of the syndrome clinical picture.