Gene-echocardiography: refining genotype-phenotype correlations in cardiomyopathy patients with restrictive phenotype

Abstract Background The restrictive phenotype, the least frequent and genetically complex form of cardiomyopathy, is the focus of this investigation. The aim is to clarify the association between restrictive phenotype and genetic variants in cardiomyopathy patient. Methods We utilized whole-exome sequencing in a cohort of 568 cardiomyopathy patients and performed echocardiographic evaluations to identify restrictive phenotypes. Comprehensive analysis of cardiac characteristics and functionality was also undertaken. Results Among the cohort, 33 patients exhibited a restrictive phenotype. These patients were distributed as follows: 7 within the restrictive cardiomyopathy group (RCM), 20 in the hypertrophic cardiomyopathy group (HRCM), and 6 in the dilated cardiomyopathy group (HDRCM). A notable prevalence of gene mutations, mainly in the MYBPC3 gene, was found in these individuals. We observed that mutation carriers, characterized by smaller aortic sinus dimension, demonstrated an association with the mutation and diminished myocardial work. Furthermore, MYBPC3 mutation carriers showed a thicker ventricular wall and a higher predisposition for septal hypertrophy. Both HRCM and HDRCM groups displayed consistent hypertrophic manifestations, with the latter demonstrating a higher frequency of interventricular septal hypertrophy. The 5-year survival rate was calculated at 54.5%, with gene mutations not significantly affecting longevity. Conclusion Genetic factors profoundly influence the restrictive phenotype of cardiomyopathy. There is a strong link between restrictive phenotype and genetic variants in cardiomyopathy, providing a foundation for more accurate genetic testing and personalized management of patients. The emerging "gene-echocardiography" concept may refine the accuracy and productivity of genetic counseling and testing in cardiomyopathy.