Adult-onset SMALED2 due to a novel BICD2 mutation presenting with asymmetrical lower limb involvement

: Heterozygous variants in the bicaudal D homolog 2 gene (BICD2) are associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). This disease is usually characterized by congenital or early-onset muscle weakness and atrophy of the lower extremities with benign or slow progression. We herein described an autosomal dominant inherited pedigree with SMALED2 in which the affected individuals presented with late adult-onset muscle weakness and wasting in the lower extremities. Obviously asymmetrical involvement of the lower limbs was observed in 3 individuals. Muscle magnetic resonance imaging revealed considerable fatty infiltrations in the middle compartment of the lower legs, including the soleus and tibialis posterior muscles. Muscle biopsy samples displayed a neurogenic pattern, but some chronic myopathy-like features were also observed. A novel heterozygous missense mutation (c.361C>G) was identified in a highly-conserved motif of BICD2. Patients with SMALED2 can present with late adult-onset and asymmetrical involvement of the lower limbs. The present study expands the clinical and mutational spectrum of SMALED2.