Clinical spectrum and follow-up in six individuals with Lamb-Shaffer syndrome (SOX5)

Lamb–Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder caused by heterozygous loss of function genetic alterations in SOX5, which result in haploinsufficiency. It is now recognized that the SOX family plays pivotal roles in many developmental and pathological processes by governing cell type‐specific genetic programs, which drive many crucial biological processes, including sex determination, neurogenesis, and skeletogenesis. Clinically, LAMSHF syndrome is mainly characterized by developmental delay, speech delay, intellectual disability, and behavioral disturbances, with other corroborating features such as ophthalmologic and skeletal abnormalities. We report clinical and molecular data of six individuals from four families, carrying SOX5 alterations. The description of new patients is fundamental to increase our knowledge of these disorders, to precisely define molecular characteristics and clinical phenotype, the evolution over time, comorbidities, and possible genotype–phenotype correlations.