Infantile Hypertrophic cardiomyopathy: steps towards an evidence-based approach to genetic testing

For decades, hypertrophic cardiomyopathy (HCM) in children was seen as a condition distinct from adult-onset HCM, characterised by severe disease with poor outcomes, and caused largely by inborn errors of metabolism and malformation syndromes.In the last 10 years, however, this notion has been largely debunked, with the demonstration that most cases of childhood-onset HCM beyond infancy (the first year of life) are caused by variants in the same sarcomeric genes that cause adult HCM and with short and medium-term outcomes much more in keeping with those in adult cohorts. [1][2]2][3] This has led to a paradigm change in clinical practice, with the most recent European and North American clinical practice guidelines now recommending genetic testing for all patients with a diagnosis of HCM, regardless of age. 4,5Indeed, the overall yield of genetic testing in childhood HCM is higher than in adult populations. 1,6Nearly one quarter of HCM diagnosed during childhood presents in infancy 7,8 and while the underlying aetiology, natural history, and outcomes in this group of patients is extremely variable, 1,7,9 a substantial minority of infant-onset HCM is also caused by sarcomeric mutations, and it is now recognised that although syndromic disease is more commonly seen in these very young patients, the aetiology of disease is more similar than different to that seen in adulthood. 1,6Despite this, the best approach to genetic testing remains unclear in this patient population.