Cor Vasa 2020, 62(3):272-278 | DOI: 10.33678/cor.2020.023

(Complex approach towards patients with hypertrophic cardiomyopathy and indications to genetic testing)

Jiří Bonaventura^a, Alice Krebsová^b, Veronika Zoubková^c, Pavel Votýpka^c, Petra Peldová^c, Jana Petřková^d, Josef Kautzner^b, Milan Macek Jr.^c, Josef Veselka^a

^a Kardiologická klinika, 2. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice v Motole, Praha

^b Centrum dědičných kardiovaskulárních onemocnění, Klinika kardiologie, Institut klinické a experimentální medicíny, Praha

^c Ústav biologie a lékařské genetiky, 2. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice v Motole, Praha

^d I. interní klinika - kardiologická, Ústav lékařské genetiky, Ústav patologické fyziologie, Lékařská fakulta Univerzity Palackého a Fakultní nemocnice Olomouc

Hypertrophic cardiomyopathy (HCM) is one of the most frequent inherited cardiac disorders with an estimated prevalence of 1 in 500 up to 1 in 200 individuals. The phenotypic heterogeneity of HCM corresponds with the marked heterogeneity in the underlying genotype. Multidisciplinary approach to HCM patients is needed and includes the collaboration of cardiologists with molecular genetics, clinical genetics, paediatric cardiologists and other specialists. Advances in contemporary DNA-sequencing methodology make gene-based diagnosis increasingly feasible in routine clinical practice. It allows rapid analysis of large multigene testing panels (e.g. cardiovascular gene panels, whole-exome sequencing [WES], and whole-genome sequencing [WGS]). Screening of large number of genes does not necessarily result in an identification of pathogenic/likely pathogenic DNA variants (P/LP) and many genetic variants of uncertain significance (VUS) are identified. Genetic testing may lead to individualized therapy in some cases, but is mainly a useful tool for family cascade screen- ing and assessing their risk for HCM. Nevertheless, documentation of P/LP variant in a relative does not necessarily lead to development of overt clinical disease due to variable penetrance and expressivity of DNA variants. The complex interpretation of multidisciplinary findings, genetic results, and family cascade screening belongs to tertiary referral centres with corresponding experience and availability of all subspecialties.

Keywords: Cascade screening, Genetic consultation, Genetic syndrome, Hypertrophic cardiomyopathy, Molecular genetic testing, Pathogenic DNA variant

Received: February 20, 2020; Revised: February 20, 2020; Accepted: March 28, 2020; Published: July 29, 2020  Show citation