An Update on 3M Syndrome: Review of Clinical and Molecular Aspects and Report of Additional Families

Abstract

3M syndrome is a rare autosomal recessive disorder characterized by short stature and recognizable facial and musculoskeletal features. Pathogenic variants in the CUL7, OBSL1, and CCDC8 genes are implicated in the pathogenesis of 3M syndrome. In this review, we discuss the history, epidemiology, molecular basis, clinical features, and management strategies for 3M syndrome. Moreover, we report on 11 new patients (from 9 unrelated families) with short stature and dysmorphic features consistent with 3M syndrome, in whom we identified five novel pathogenic variants expanding the genetic landscape of the syndrome. Finally, we have reviewed the molecularly confirmed cases of 3M published to date.