Genetic Testing in Patients with Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.

Screening for Hypertrophic Obstructive Cardiomyopathy in Patients With Panic Disorder: A Case Report

“…Screening for HOCM entails looking for the most involved genes, which include MYH7 , cardiac myosin binding protein-C ( MYBPC3 ), cardiac troponin T ( TNNT2 ), and cardiac troponin I ( TNNI3 ), with the first two accounting for almost 80% of all HOCM patients [ 17 ]. MYH7 and MYBPC3 contain sequences that encode for sarcomeres or sarcomere-associated proteins, in which next-generation sequencing (NGS) can rapidly analyze for mutations in these genes [ 18 , 19 ]. Patients with suspected genetic etiologies of left ventricular hypertrophy may also have mutations that are separate from HOCM and can include Fabry disease, Noonan syndrome, and other lysosomal storage disorders [ 20 ].…”

Post-systolic shortening index by echocardiography evaluation of dyssynchrony in the non-dilated and hypertrophied left ventricle

“…Amongst HCM patients, diagnosis was confirmed by cardiac magnetic resonance in 29 [7], and by subsequent operative histology findings in 3 patients, while the remaining were diagnosed by echocardiography alone (3 because of having an implantable cardiac defibrillator). Eleven patient underwent genetic testing, with PLOS ONE pathogenic mutation present in 7 subjects [8]. In addition, we recruited, as a control group, healthy subjects without valvular, structural, or coronary artery disease and normal systolic and diastolic function.…”

Overview of Obstructive Hypertrophic Cardiomyopathy

“…1 A genetic test can diagnose HCM in some patients, but the results are inconclusive in others. 2 It is important to note that the results of a genetic test need to be carefully interpreted by geneticists and clinicians, in the context of the patient's clinical condition, before being used for further management of the patient and their family. 2 HCM is diagnosed in between one in 200 and one in 500 people.…”

“…2 It is important to note that the results of a genetic test need to be carefully interpreted by geneticists and clinicians, in the context of the patient's clinical condition, before being used for further management of the patient and their family. 2 HCM is diagnosed in between one in 200 and one in 500 people. 3 The condition can worsen over time, with the heart becoming enlarged, resulting in several complications due to cardiac hypertrophy, which may present years after the initial diagnosis.…”