Dilated cardiomyopathy - three brothers and a BAG3 mutation

Abstract

We report a case of left ventricular non-compaction (LVNC) associated with hereditary autosomal dominant polycystic kidney disease (ADPKD). A 24 year-old male was referred with a six month history of New York Heart Association (NHYA) Class III exercise intolerance. Past medical history included stage III chronic kidney disease secondary to autosomal dominant polycystic kidney disease (ADPKD). Apart from ADPKD there was no other family history. Echocardiogram showed severe left ventricular dilatation (left ventricular end diastolic volume 240 mL) with ejection fraction of 60%. There was posterior leaf mitral valve prolapse (MVP) and grade 4/4 mitral regurgitation. Cardiac magnetic resonance imaging (cMRI) confirmed non-compacted to compacted myocardium ratio 3.4 (N < 2.3). LVNC is an inherited cardiac cause of ventricular failure. Prominent ventricular muscle trabeculations with corresponding deep recesses communicating with the left ventricular cavity are the hallmark of the condition. Multiple genetic loci have been implicated, including loci that overlap with other types of cardiomyopathies. ADPKD is an hereditary cause of chronic kidney disease secondary to mutations in the PKD1 and PKD2 genes. ADPKD is characterised by the presence of multiple renal cysts. Cardiovascular complications have the greatest impact on morbidity and mortality in patients with ADPKD. Valvular abnormalities especially MVP are common. Boulter et al (2001) showed that homozygote deletion of PKD1 in mice resulted in severe cardiovascular anomalies that included hypertrabeculation, myocardial thinning, and septation defects. Our case suggests the existence of a syndromic association between ADPKD, LVNC, and possibly MVP that needs further elucidation at both clinical and molecular levels.