Penetrance of Hypertrophic Cardiomyopathy in Children and Adolescents: A 12 Year Follow-Up Study of Clinical Screening and Predictive Genetic Testing

Morten K. Jensen; Ole Havndrup; Michael Christiansen; Paal S. Andersen; Birgitte Diness; Anna Axelsson; Flemming Skovby; Lars Køber;
Henning Bundgaard

CIRCULATIONAHA.111.090514

Published online before print November 28, 2012

Abstract

Background—The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has only been sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives to patients with HCM.

Methods and Results—Ninety probands and 361 relatives were included in a family-screening program for HCM (1994-2001). Eleven sarcomere genes, CRYAB, α-GAL and Titin were screened. Sixty-six relatives and four probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age 12±5 years), and 26 had unknown genetic status, i.e. relatives from families without identified mutations (n=21) or not tested (n=5) (age 11±5 years). Twenty-eight (42%) non-carriers (age 10±4 years) served as controls. Two out of 38 (5%) child relatives at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12±1 years follow-up two out of the 36 (6%, CI 2-18%) at risk child relatives, who were phenotype-negative at inclusion, had developed the HCM phenotype at the age of 26 and 28 years. During follow-up none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact.

Conclusions—The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years follow-up. The finding of phenotype conversion in the mid-twenties warrants continued screening to extend into adulthood. Forty-two percent of the child relatives were non-carriers, and repeated clinical follow-up could safely be limited to the remaining children.