Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort

Sci Rep. 2020 Nov 26;10(1):20610. doi: 10.1038/s41598-020-77124-9.

Abstract

The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre-excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype, genotype and clinical outcomes of a South-Asian PRKAG2 cardiomyopathy cohort over a 7-year period. Clinical, electrocardiographic, echocardiographic, and cardiac MRI data from 22 individuals with PRKAG2 variants (68% men; mean age 39.5 ± 18.1 years), identified at our HCM centre were studied prospectively. At initial evaluation, all of the patients were in NYHA functional class I or II. The maximum left ventricular wall thickness was 22.9 ± 8.7 mm and left ventricular ejection fraction was 53.4 ± 6.6%. Left ventricular hypertrophy was present in 19 individuals (86%) at baseline. 17 patients had an WPW pattern (77%). After a mean follow-up period of 7 years, 2 patients had undergone accessory pathway ablation, 8 patients (36%) underwent permanent pacemaker implantation (atrio-ventricular blocks-5; sinus node disease-2), 3 patients developed atrial fibrillation, 11 patients (50%) developed progressive worsening in NYHA functional class, and 6 patients (27%) experienced sudden cardiac death or equivalent. PRKAG2 cardiomyopathy must be considered in patients with HCM and progressive conduction system disease.

MeSH terms

  • AMP-Activated Protein Kinases / genetics*
  • Adolescent
  • Adult
  • Asian People / genetics*
  • Atrial Fibrillation / genetics
  • Cardiomyopathies / genetics*
  • Child
  • Cohort Studies
  • Death, Sudden, Cardiac
  • Echocardiography / methods
  • Electrocardiography / methods
  • Female
  • Genetic Variation / genetics
  • Humans
  • Hypertrophy, Left Ventricular / genetics
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Ventricular Function, Left / genetics
  • Young Adult

Substances

  • PRKAG2 protein, human
  • AMP-Activated Protein Kinases