Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is a heritable myocardial disease with age-related penetrance. Current guidelines recommend clinical screening of relatives beginning at 10 years of age, but the clinical value of this approach has not been systematically evaluated.

Methods: Anonymized clinical data were collected from children referred for family screening between 1994 and 2017 after diagnosis of HCM in a first-degree relative.

Results: Of 1198 consecutive children (≤18 years of age) from 594 families who underwent serial evaluation (median, 3.5 years; interquartile range, 1.2-7), 32 individuals met diagnostic criteria at baseline (median maximal left ventricular wall thickness, 13 mm; interquartile range, 8-21 mm), and 25 additional patients developed HCM during follow-up. Median age at diagnosis was 10 years (interquartile range, 4-13 years); 44 (72%) were ≤12 years of age. Median age of affected patients at the last follow-up was 14 years (interquartile range, 9.5-18.2 years). A family history of childhood HCM was more common in those patients diagnosed with HCM (n=32 [56%] versus n=257 [23%]; P<0.001). Eighteen patients (32%) were started on medication for symptoms; 2 (4%) underwent a septal myectomy; 14 (25%) received an implantable cardioverter-defibrillator; 1 underwent cardiac transplantation; 2 had a resuscitated cardiac arrest; and 1 died after a cerebrovascular accident.

Conclusions: Almost 5% of first-degree child relatives undergoing screening meet diagnostic criteria for HCM at first or subsequent evaluations, with the majority presenting as preadolescents; a diagnosis in a child first-degree relative is made in 8% of families screened. The phenotype of familial HCM in childhood is varied and includes severe disease, suggesting that clinical screening should begin at a younger age.

Keywords: cardiomyopathies; child; death, sudden; genetics; mass screening.

Figure 1.

Genetic testing in pediatric patients with hypertrophic cardiomyopathy (HCM). A, Genetic testing in patients referred for clinical screening. B, Genetic testing in patients diagnosed with HCM through family screening. G+ indicates genetically tested and pathogenic sarcomeric mutation identified; G null, genetically tested and no pathogenic sarcomeric mutation identified; and Pos, positive.

Figure 2.

Progression of left ventricular hypertrophy during childhood. A, Change in absolute maximal left ventricular wall thickness (MLVWT) during childhood in those patients diagnosed through clinical screening (n=48). B, Change in MLVWT z score during childhood in those patients diagnosed through clinical screening (n=48). C, Change in absolute MLVWT during childhood in those patients diagnosed in preadolescence (≤12 years of age; n=32). D, Change in absolute MLVWT during childhood in those patients diagnosed in adolescence (≥13 years of age; n=16). E, Change in absolute MLVWT during childhood in those patients diagnosed at baseline evaluation (n=32). F, Change in absolute MLVWT during childhood in those patients diagnosed during follow-up (n=25). Connected dash line represents serial measurements from a single patient. Red line represents locally weighted scatterplot smoothing.