Cardiovascular genetics: the role of genetic testing in diagnosis and management of patients with hypertrophic cardiomyopathy

Abstract

Genetic testing in hypertrophic cardiomyopathy (HCM) is a valuable tool to manage patients and their families. Genetic testing can help inform diagnosis and differentiate HCM from other disorders that also result in increased left ventricular wall thickness, thereby directly impacting treatment. Moreover, genetic testing can definitively identify at-risk relatives and focus family management. Pathogenic variants in sarcomere and sarcomere-related genes have been implicated in causing HCM, and targeted gene panel testing is recommended for patients once a clinical diagnosis has been established. If a pathogenic or likely pathogenic variant is identified in a patient with HCM, predictive genetic testing is recommended for their at-risk relatives to determine who is at risk and to guide longitudinal screening and risk stratification. However, there are important challenges and considerations to implementing genetic testing in clinical practice. Genetic testing results can have psychological and other implications for patients and their families, emphasising the importance of genetic counselling before and after genetic testing. Determining the clinical relevance of genetic testing results is also complex and requires expertise in understanding of human genetic variation and clinical manifestations of the disease. In this review, we discuss the genetics of HCM and how to integrate genetic testing in clinical practice.

Echocardiographic evaluation of the Athlete’s heart

“…99 the growing number of known sarcomeric gene variants has yielded up to 60% identification of HCM when utilizing genetic testing alone. 103 The primary variants known today are "HCM-MYBPC3, MYH7, TNNT2, TNNI3, TPM1, ACTC1, MYL2, and MYL3-and currently four genes with moderate evidence supporting their causal role in HCM-CSRP3, TNNC1, ACTN2, and JPH2." 103 Screening for these genes, in conjunction with thorough review of family history and multimodality imaging, is highly effective in reducing misclassification of significant pathologies as AH.…”

Incorporating Cascade Effects of Genetic Testing in Economic Evaluation: A Scoping Review of Methodological Challenges

“…Genetic testing is a powerful diagnostic tool that can be applied to diseases affecting any organ system in the body [ 1 , 2 , 3 , 4 ]. These diseases may be hereditary, or mutations can arise de novo.…”

“…Identification of a genetic diagnosis in a patient facilitates more appropriate management and enables physicians to better approximate patients’ prognoses. Importantly, identifying a genetic diagnosis in a patient enables genetic testing or clinical screening of their family members to determine whether they may also be at risk of developing the disease [ 3 , 5 ]. The first person in a family to undergo genetic testing is known as the proband, index case, or index patient, and the process of subsequently testing or screening relatives is called cascade testing or cascade screening.…”

Atrial Fibrillation in Hypertrophic Cardiomyopathy

“…ГКМП -аутосомно-доминантное заболевание, среди причин которого рассматривают мутации генов, кодирующих регуляторные, сократительные и структурные белки кардиальных саркомеров [7][8][9]. К настоящему в ремени у больных с ГКМП выявлено как минимум 13 генов с более чем 1500 мутациями, экспрессированными преимущественно или исключительно в тканях сердца [5,[9][10][11].…”