Clinical and Genetic Spectrums of Pediatric Cardiomyopathies: Experience from a Tertiary Pediatric Cardiology Centre in Hong Kong

Abstract

Abstract Background Pediatric cardiomyopathies are rare conditions associated with substantial morbidity and mortality. This study aims at reporting the clinical and genetic spectrums of pediatric cardiomyopathy in the single tertiary centre in the Hong Kong. Study Design : All primary cardiomyopathy patients who were ≤ 18 years old and followed up in our pediatric cardiology clinic were analyzed. Whole exome sequencing was offered to patients who did not have molecular diagnosis identified with prior single gene or panel testing. Results 45 unrelated patients were identified, including 19 (42.2%) with hypertrophic cardiomyopathy, 20 (44.4%) with dilated cardiomyopathy, three (6.7%) with restrictive cardiomyopathy, and three (6.7%) with left ventricular non-compaction. Pathogenic and likely pathogenic variants were identified in 19 of 41 patients, resulted in an overall diagnostic yield of 46.3%. Among these patients, nine (47.4%) patients had an inherited disorder of the RAS/MASPK signal transduction pathway (BRAF, LZTR1, PTPN11 and RAF1), six (31.6%) harbored mutations in gene associated with primary cardiomyopathy (BAG3, MYBPC3, MYH7, MYL2, RBM20 and TNNT2), and four (21.1%) were diagnosed with syndromic or systemic conditions other than RASopathy (LAMP2, NONO and TAZ). In addition, eight patients carried a variant of uncertain significance (VUS). The presence of syndromic features or extracardiac manifestations was associated with a positive genotype. Conclusions The overall diagnostic yield of genetic evaluation was 46%. The study reinforced the utility of genetic assessment in phenotypically confirmed pediatric cardiomyopathy patients, especially for those with syndromic features. Novel mutation of our cohort was reported and described.