Non-5q Spinal Muscular Atrophy in a Patient with a Novel BICD2 Missense Variant

Variants in BICD cargo adapter 2 (BICD2) cause autosomal dominant spinal muscular atrophy with lower extremity dominance (SMALED2) which is characterized with lower extremity muscle weakness and atrophy. We describe a novel, heterozygous BICD2 variant (c.1661T>C, [p.Leu554Pro]) in a 21-month-old female patient with a more severe phenotypic presentation than the typical SMALED2 expression including arthrogryposis multiplex congenita, absent deep tendon reflexes, respiratory insufficiency, and cerebral depression. The variant p.Leu554Pro is located just outside of a domain that interacts with the motor protein KIF5A. The detailed neuro-phenotyping and clinical course presented here expand the understanding of BICD2 related disease.