Development of the New Zealand cardiac inherited disease registry

Abstract

Multi-gene testing panels provided by clinical laboratories have become increasingly available and affordable and have been used since 2008 in South Australia. We audited consecutive patients diagnosed with cardiomyopathy or channelopathy and referred to the SA Clinical Genetics Service for genetic testing between 1 January 2008 and 31 December 2013. 66 probands with cardiac channelopathy were identified, 58 with Long QT syndrome (LQTS), 5 with Brugada syndrome, and 3with other disorders. 62 of these probandswere tested. The 60 completed tests identified 28% with pathogenic variants (All LQTS 29%, familial LQTS 43%, sporadic LQTS 20%) and 13% with variants of uncertain significance (VUS). Proband testing in channelopathy enabled cascade testing in 41 patients, 10 for confirmatory and 31 for predictive testing. 94 probandswith cardiomyopathywere identified, 73 with hypertrophic cardiomyopathy (HCM), 10 with dilated cardiomyopathy, 4 with arrhythmogenic ventricular dysplasia, and 7 with other cardiomyopathies. 77 of these probands were tested. The 70 completed tests identified 47% with pathogenic variants (All HCM 46%, familial HCM 74%, sporadic HCM 22%) and 14% with a VUS. Proband testing in cardiomyopathy enabled cascade testing in 24 patients, 3 for confirmatory and 21 for predictive testing. We found that the yield of genetic testing for cardiomyopathies was similar to published rates, but our yield of genetic testing for cardiac channelopathies was lower than published rates. VUS were found in a considerable proportion of patients. In vivo functional data exist for few variants.