Clinical and Genetic Screening for Hypertrophic Cardiomyopathy in Paediatric Relatives: Changing Paradigms in Clinical Practice

Abstract

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality in children. While the aetiology is heterogeneous, most cases are caused by variants in the genes encoding components of the cardiac sarcomere, which are inherited as an autosomal dominant trait. In recent years, there has been a paradigm shift in the role of clinical screening and predictive genetic testing in children with a first-degree relative with HCM, with the recognition that phenotypic expression can, and often does, manifest in young children and that familial disease in the paediatric age group may not be benign. The care of the child and family affected by HCM relies on a multidisciplinary team, with a key role for genomics. This review article summarises current evidence in clinical and genetic screening for hypertrophic cardiomyopathy in paediatric relatives and highlights aspects that remain to be resolved.

Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future

“…Previously, there was controversy regarding cascade genetic testing and clinical screening in first-degree relatives of the proband aged less than 10 years, in the absence of family history of premature death from HCM, participation in competitive sports, or any clinical aspect that suggests early HCM [ 53 ]. It is now recommended to test them regardless of their age or risk factors according to recent data revealing that a significant percentage of HCM patients can manifest before 10 years of age with high morbidity and mortality regardless of their risk factors [ 5 , 6 ].…”

“…It is now recommended to test them regardless of their age or risk factors according to recent data revealing that a significant percentage of HCM patients can manifest before 10 years of age with high morbidity and mortality regardless of their risk factors [ 5 , 6 ]. Additionally, the data showed the clinical significance and the minimum negative impacts of testing on the child in the context of multidisciplinary care that includes psychosocial support [ 53 ].…”

Hypertrophic Cardiomyopathy—Current Challenges and Future Perspectives

“…Melas et al describe the main genes implicated in the aetiology of HCM, define the role of diagnostic genetic panels (e.g., next-generation sequencing, whole-exome sequencing, and whole-genome sequencing), and introduce the potential of gene therapy in patients with HCM [ 10 ]. In contrast, Lawley et al emphasize the importance of conducting clinical and genetic screening among paediatric family members of individuals with HCM [ 11 ]. Genetic testing should always be prescribed after comprehensive genetic counselling, which aims to educate patients and their families about the benefits and constraints of genetic testing, the genetic aspects related to the disease, and the potential for passing on the condition to their relatives [ 1 ].…”