Clinical and Genetic Landscape of IGHMBP2-Related Disorders: From Novel Variants to Phenotypic Insights

Pathogenic variants in IGHMBP2 have been associated with spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Autosomal Recessive Charcot–Marie–Tooth disease type 2S (AR-CMT2S), as well as a relatively wide spectrum of rare, atypical phenotypes. We describe clinical and molecular features of five patients who have diverse clinical findings associated with known and novel IGHMBP2 pathogenic variants. Genotype–phenotype correlations are evident, highlighting the association of specific variants with SMARD1 or AR-CMT2S. This study expands the spectrum of the IGHMBP2-related disease and highlights the necessity to study diverse populations to enhance diagnostic accuracy and refine genotype–phenotype correlations.