Abstract

Genetic testing in Hypertrophic Cardiomyopathy (HCM) is a published guideline-based recommendation. In the last decade, next generation sequencing has broadened testing options; expanded panels now contain not only the core HCM genes, but also a wide range of syndromic and metabolic etiologies.

Patients with a clinical suspicion of HCM referred for genetic testing likely represent a more general, unselected HCM population compared to previously published HCM cohorts.

We describe the diagnostic findings and variables significantly affecting the genetic testing yield in a heterogeneous HCM patient cohort.

A total of 1376 cases with a clinical suspicion of HCM were sent for genetic testing. For half the patients (51%), a broad cardiomyopathy panel was ordered; 46% had an HCM specific panel and 3% had a comprehensive cardiology panel (cardiomyopathy and arrhythmia genes).

> Cardiomyopathy Panel

The overall diagnostic yield was 26.2%. One in 20 patients had a diagnostic finding in a gene not included on the HCM panel, further highlighting the heterogeneity of this cohort and the importance of utilizing broad panels in certain clinical circumstances.

Keywords: Hypertrophic cardiomyopathy (HCM), genetic testing, diagnostic yield, genetic heterogeneity

Authors: Juha Koskenvuo, Julie Hathaway, Inka Saarinen, Jonna Tallila, Eija H Seppälä, Sari Tuupanen, Hannu Turpeinen, Tiia Kangas-Kontio, Jennifer Schleit, Johanna Tommiska, Eveliina Salminen, Pertteli Salmenperä, Johanna Sistonen, Mikko Muona, Massimiliano Gentile, Ville Kytölä, Samuel Myllykangas, Jussi Paananen, Tero-Pekka Alastalo