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.