Cohen syndrome and neutropenia: Unveiling a novel VPS13B variant and literature review

Objective: To report a novel VPS13B variant and to describe the prevalence of neutropenia and immunological clinical features in patients with Cohen syndrome (CS). Study design: We conducted a comprehensive search focusing on CS and neutropenia using PubMed, Embase, Google Scholar and the Human Gene Mutation Database. The key words were "Cohen syndrome" AND "neutropenia," "VPS13B″ AND "neutropenia," "COH1" AND "neutropenia." Inclusion criteria required articles to be in English, to report a confirmed VPS13B variant (or the previously named COH1) and to provide information on clinical phenotypes. Results: The literature review identified 54 reports that met the inclusion criteria. The majority of CS patients (226/293; 77.1 %) presented with neutropenia, with notable differences according to ethnicity. Caucasians had reduced neutrophil levels in 90.6 % of cases, whereas Arabs and Asians had reduced neutrophil levels in only 58.7 % and 47.1 % of cases, respectively. There was no clear genotype-phenotype correlation with regard to neutropenia. Although few serious infections were reported, oral mucosal involvement and its sequelae were common. Dysimmune phenomena were observed in seven cases. We also report the case of a seven-year-old Italian child with a novel compound heterozygosity in the VPS13B gene who was previously diagnosed with isolated autoimmune neutropenia. Conclusions: Clinical, ethnic and immunological data suggest that neutropenia in CS may be part of a complex immune dysregulation. Further immunological studies may help in the early diagnosis and treatment of autoimmune and mucosal involvement to prevent potential complications.