Evaluation of genetic causes of cardiomyopathy in childhood

Abstract

Cardiomyopathy frequently has a genetic basis. In adults, mutations in genes encoding components of the sarcomere, cytoskeleton, or desmosome are frequent genetic causes of cardiomyopathy. Although children share these causes, ~30% of children have an underlying metabolic, syndromic, or neuromuscular condition causing their cardiomyopathy, making the aetiologies more diverse in children as compared with adults. Although some children present with obvious signs or symptoms of metabolic, syndromic, or neuromuscular disease, other cases may be quite subtle, requiring a high level of suspicion in order to diagnose them. In general, the younger the child, the more extensive the differential. Advantages of identifying the underlying genetic cause of cardiomyopathy in the paediatric population include confirming the diagnosis in ambiguous cases, facilitating appropriate surveillance and management of cardiac and extra-cardiac diseases, providing prognostic information, and establishing the genetic basis in the family, thereby allowing the identification of at-risk relatives and institution of appropriate family screening as indicated. For these reasons, genetic testing is increasingly recognised as standard of care, and guidelines for genetic counselling, testing, and incorporation of family-based risk assessment have been established. Therapies aimed at treating specific genetic aetiologies of cardiomyopathy are emerging and are exciting new developments that require increasingly sophisticated approaches to diagnosis. As genetic testing capabilities continue to expand technically, careful interpretation, knowledgeable clinical utilisation, and appropriate dissemination of genetic information are important and challenging components of clinical care.

Keywords: Mutation; genetic syndrome; genetic variant; sarcomere.