Key result
Genotype-positive family status is linked to a ~178% higher 5-year risk of pediatric HCM diagnosis.
Why the study?
Adult relatives with genotype-negative HCM have a lower screening yield suggesting one-off assessment may suffice, but whether this applies to pediatric relatives was unknown.
Does clinical screening yield diagnoses of hypertrophic cardiomyopathy in pediatric relatives of genotype-negative families compared to genotype-positive families?
Cohort (n=696)
Does clinical screening yield diagnoses of hypertrophic cardiomyopathy in pediatric relatives of genotype-negative families compared to genotype-positive families?
Absolute Event Rate: 11.1% vs 4%
p-value: p=0.010
Clinical screening in pediatric relatives of genotype-negative hypertrophic cardiomyopathy families yields a diagnosis in 8% of families, supporting the need for universal screening irrespective of genotype status.
Supports continued clinical screening of pediatric relatives even when families are genotype-negative; leaves open whether screening intervals can be safely modified.
BACKGROUND: Serial clinical screening of first-degree relatives of individuals with hypertrophic cardiomyopathy (HCM) is recommended. A lower yield of screening in adult relatives with genotype-negative disease might mean a one-off assessment is appropriate, but it is unknown if these findings can be extrapolated to pediatric relatives. OBJECTIVES: This study aims to determine the yield of clinical screening in pediatric relatives of genotype-negative families. METHODS: Clinical and outcome data were collected from 404 children (≤18 years) from 227 genotype-positive (G+) families and 292 children from 170 genotype-negative (G-) families referred for family screening. RESULTS: Individuals from G- families were less likely to have a family history of childhood disease or sudden cardiac death. Over a follow-up of 68.9 ± 49.7 months, a diagnosis was made in 66 (9.5%) individuals with a higher 5-year cumulative incidence in individuals from G+ families than in those from G- families (11.1 [95% CI: 8.3-15.0] vs 4.0 [95% CI: 1.7-9.1]; P = 0.010). A diagnosis was made in 41 (18.1%) G+ families screened compared with 14 (8.2%) G- families (P < 0.001). The age and clinical features at diagnosis did not differ. Over a follow-up of 8.6 ± 4.1 years, there was no difference in the incidence of death or arrhythmic events, but symptoms (19 [36.5%] vs 2 [14.3%]; P = 0.034) and implantable cardioverter-defibrillator implantation (22 [42.3%] vs 1 [7.1%]; P = 0.014) were more common in the G+ group. CONCLUSIONS: The 5-year cumulative diagnostic yield of screening childhood relatives is twofold higher in G+ families, but a childhood diagnosis was still made in 8% of G- families. These results support the need for universal screening of first-degree childhood relatives with HCM irrespective of genotype status. Further work to determine whether the frequency or timing of screening can be modified is required.
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Norrish et al. (2026) conducted a cohort in Hypertrophic cardiomyopathy (n=696). Genotype-positive family status vs. Genotype-negative family status was evaluated on 5-year cumulative incidence of diagnosis (p=0.010). Children from genotype-positive families had a higher 5-year cumulative incidence of hypertrophic cardiomyopathy diagnosis than those from genotype-negative families (11.1% vs 4.0%; P=0.010).
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