SMALED2 with BICD2 gene mutations: report of two cases and portrayal of a classical phenotype

Abstract The spinal muscular atrophies (SMA) affect lower motor neurons leading to important muscle atrophy and paralysis. Some cases of SMA affect mostly the lower limbs and are called autosomal dominant spinal muscular atrophy, lower extremity predominant (SMALED). So far, two genes have been identified to cause this phenotype, DYNC1H1 (SMALED1) and BICD2 (SMALED2). This pathology is rare, but patients exhibit classical features which should be recognised by physicians. We present two unrelated cases of SMALED2 with previously described c.320C>T BICD2 mutations. Our cases exhibit non-progressive weakness and atrophy of the lower limbs associated with contractures and unique muscle MRI findings suggestive of classical SMALED2. We also performed an extensive review of the literature to present the classical and atypical phenotypes of BICD2. Indeed, some features appear to be highly suggestive of the disease, including upper limb sparing, sparing of the adductors muscles on physical examination and MRI, congenital contractures and normal nerve conductions studies.