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

Ann Neurol. 2020 Apr;87(4):487-496. doi: 10.1002/ana.25704.


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.

Publication types

  • Review

MeSH terms

  • Genetic Association Studies
  • Genotype
  • Humans
  • Microtubule-Associated Proteins / genetics*
  • Mobility Limitation
  • Muscle Weakness
  • Muscular Atrophy
  • Mutation
  • Phenotype
  • Respiratory Insufficiency
  • Severity of Illness Index
  • Spinal Muscular Atrophies of Childhood / genetics*
  • Spinal Muscular Atrophies of Childhood / physiopathology*


  • BICD2 protein, human
  • Microtubule-Associated Proteins