Four Looks to a Gene (P1-8.013)

Abstract

<h3>Objective:</h3> We present a family with varied clinical presentations of a genetically confirmed muscular dystrophy. <h3>Background:</h3> A 41-year-old male presented with several years of muscle fatigue, pain and twitching across his chest and proximal muscles. He was diagnosed with neuronal hyperexcitability. Exam showed normal muscle strength, but there were visible rippling in proximal muscles. Cardiac workup was unrevealing. EMG showed nonspecific myopathic features and CPK was in the 400’s. His 9-year-old son has been diagnosed with muscular dystrophy and two daughters has elevated CPKs. Our patient was genetically confirmed to have a heterozygous C.80G&gt;A(p.Arg27Gln) mutation in the Caveolin-3 gene via Invitae muscular dystrophy testing. This missense mutation causes an amino acid change from Arg to Gln in the Caveolin 3 protein, which leads to a decrease of Cav-3 protein expression in skeletal muscle tissue. It has an autosomal dominant inheritance pattern. <h3>Design/Methods:</h3> Not applicable <h3>Results:</h3> Mutations in the Caveolin-3 gene have been described in a broad spectrum of clinical presentations including limb girdle muscular dystrophy, rippling muscle disease, idiopathic persistent hyperCKemia, and distal myopathy. Muscular dystrophy can present with a wide variety of phenotypes and there is even variation within the same gene mutations, as is the case in caveolin 3 mutations. This may lead to delay in diagnosis and supportive treatments that a family may require. The Invitae muscular dystrophy panel can be helpful in expediting diagnosis for multiple family members. It is also important to remember that muscular dystrophy can mimic muscle hyperexcitability syndrome, as was the case in our patient with rippling muscle disease. <h3>Conclusions:</h3> Muscular dystrophy can present with distinct phenotypic variations. A good family history and awareness of clinical symptoms can be helpful for diagnosis. CAV3 mutations cause LGMD1C which can present with at least four different phenotypes. <b>Disclosure:</b> Dr. Rahimi has nothing to disclose. Dr. Memar Ardestani has nothing to disclose. Dr. Prabhu has nothing to disclose. Dr. Undavia has nothing to disclose.