The Genotypic and Phenotypic Spectrum of BICD2 Variants in Spinal Muscular Atrophy

The bicaudal D cargo adaptor 2 ( BICD2 ) gene encodes a conserved cargo adaptor protein required for dynein‐mediated transport. Inherited and de novo variants in BICD2 cause SMALED2 (spinal muscular atrophy lower extremity dominant 2), and a subset have recently been reported to cause severe, often lethal disease. However, a true genotype–phenotype correlation for BICD2 has not been performed, and cases described to date are scattered among at least 14 publications. In this review, we identify the characteristics of disease‐causing variants in BICD2 that distinguish them from benign variation and perform genotype–phenotype correlations for 99 BICD2 variant carriers from 35 families. ANN NEUROL 2020;87:487–496