101 Neuromuscular MRI in Assessment of Variants of Unknown Significance in Inherited Neuropathy and Associated Disorders

BackgroundA problem frequently faced by neurologists is the interpretation of genetic variants of unknown significance(VUS). Unlike in many muscle diseases, specific patterns of muscle involvement are not typically demonstrated on muscle MRI of inherited neuropathy patients. Imaging muscle involvement can be of assistance when assessing VUS.Case ExamplesTwo unrelated individuals with axonal CMT were identified to have a novel p.Lys554Glu DNM2 mutation. Neuromuscular MRI was consistent with the clinical findings and similar to literature descriptions, supporting the pathogenicity of this variant.Spinal Muscular Atrophy Lower Extremity Dominant (SMA-LED) due to DYNC1H1 mutations can be associ- ated with sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, with diffuse involvement at the calf level, sparing the anterior-medial muscles1 on MRI. These features were demonstrated in the imaging of a proband with SMA-LED has two mutations in DYNC1H1, one of which is novel. The novel p.His75Pro mutation was also found in his mother who has normal clinical examination and neuromuscular MRI, suggesting that the previously described p.Arg251His mutation2 was the cause of the neuromuscular phenotype in the proband.DiscussionMRI has a role supporting the diagnosis of inherited neuropathies, and in evaluating VUS.Scoto et al. Novel mutations expand the clinical spectrum of DYNC1H1-associated SMA. Neurology.2015Feb17;84:668–679Antoniadi et al. Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides high diagnostic yield.BMCMedGenet.2015Sep21;16:84.c.doherty@ucl.ac.uk