P.147 - CAV3 p.Ala93Thr pathogenic mutation causing hypertrophic cardiomyopathy

Abstract

CAV3 related disorders encompasses a great range of phenotypes, to include fixed muscle weakness due to limb girdle muscular dystrophy, rippling muscle disease, hyperCKaemia, distal myopathy, myalgia, exertion intolerance and recurrent rhabdomyolysis. Overlapping phenotypical spectrum and intrafamilial variability may pose a further challenge on caveolinopathy diagnosis. A 52 years old gentleman was referred to the Muscle Clinic at the National Hospital for Neurology and Neurosurgery at Queen Square following a recent genetic diagnosis of caveolinopathy. He was a fit and healthy long distance runner in his youth who was incidentally diagnosed with an asymptomatic murmur at his mid-40s. Five years later he developed shortness of breath, which led to the diagnosis of hypertorphic cardiomyopathy, culminating in left ventricular myectomy. Complete heart block following myectomy for which he underwent a dual chamber pacemaker insertion. The patient also had a long history (>10 years) of muscle pain in both calves. Myalgia occurred mainly at early evening and at night. The pain was severe enough to wake him up during sleep. Symptoms worsen following physical activities. He also reported to be easily fatigued. Serum creatine kinase (CK) levels were 199 IU/L (range: 38–204). Family history included a maternal cousin diagnosed with dilated cardiomyopathy at his 20s. Genetic investigation showed a heterozygous CAV3 p.Ala93Thr mutation. Here we present a patient with hypertrophic cardiomyopathy and late onset muscle pain due to a heterozygous CAV3 mutation. The reported variant has been previously associated with Leiden Muscular Dystrophy and rippling muscle disease. In this poster session, we will further explore the CAV3 phenotypical spectrum.