ClinVar

In affected members of a 3-generation family with autosomal dominant lower extremity-predominant spinal muscular atrophy (SMALED1; 158600), Harms et al. (2012) identified a heterozygous 2011A-G transition in exon 8 of the DYNC1H1 gene, resulting in a lys671-to-glu (K671E) substitution at a highly conserved residue in the tail domain of the dynein heavy chain. The mutation was not found in 500 controls or the 1000 Genomes Project. The 3 affected individuals showed waddling gait from early childhood, with awkward running due to lower limb weakness; upper limbs were not affected. Muscle atrophy and weakness confined to the lower limbs showed little progression throughout life. There was a notable strength discrepancy between knee extension and flexion, with the quadriceps showing significant weakness. Deep tendon reflexes were reduced at the knees, but normal elsewhere. Nerve conduction studies showed small motor responses and normal sensory responses; EMG showed chronic denervation. One patient had heel cord contractures and inturning feet, whereas another had fasciculations of the calves.