Clinical, immunological, and genetic spectrum of pediatric Cohen syndrome: a retrospective single-center study

Introduction: Cohen syndrome (CS) is a rare autosomal recessive multisystem disorder caused by biallelic pathogenic variants in the VPS13B gene. Although the neurodevelopmental and dysmorphic manifestations of the disease are well characterized, its immunological features remain insufficiently defined. This study aimed to evaluate the clinical, genetic, and immunological characteristics of pediatric patients with Cohen syndrome.Methods: This retrospective single-center study included six pediatric patients with molecularly confirmed Cohen syndrome who were followed between January 2024 and April 2026. Demographic characteristics, clinical manifestations, immunological findings, and genetic data were retrospectively reviewed.Results: Five patients (83.3%) were male, and the median age at diagnosis was 55 months (range, 18–114 months). A history of consanguinity and homozygous VPS13B variants were present in all patients. The most common clinical findings were microcephaly (83.3%), growth failure and/or short stature (66.7%), and neurodevelopmental impairment. Neutropenia and low serum IgM levels were identified in the same three patients (50%). In contrast, serum IgG and IgA concentrations, lymphocyte subset distributions, and specific antibody responses were preserved in all patients. Trimethoprim-sulfamethoxazole prophylaxis was initiated in three patients with neutropenia, low serum IgM levels, and recurrent infections. None of the patients required immunoglobulin replacement therapy or hematopoietic stem cell transplantation. No mortality was observed during the follow-up period.Conclusion: Neutropenia and low serum IgM levels may represent underrecognized immunological manifestations of Cohen syndrome in the absence of severe cellular or humoral immunodeficiency. The coexistence of neutropenia and low serum IgM levels in patients with recurrent infections suggests that mild humoral immune dysregulation may accompany neutropenia and potentially contribute to increased infection susceptibility. Regular immunological assessment and antimicrobial prophylaxis in selected patients may contribute to improved clinical outcomes.