Screening childhood relatives of genotype positive HCM families diagnosed 12.5%, four-fold higher than 2.9% in gene-elusive families (p<0.001).
Does clinical screening yield diagnoses in first-degree childhood relatives of patients with gene-elusive hypertrophic cardiomyopathy compared to genotype-positive families?
Clinical screening of childhood relatives of gene-elusive HCM patients still yields a diagnosis in approximately 3% of cases, supporting current guidelines for universal screening regardless of the index patient's genotype.
Absolute Event Rate: 0% vs 0%
Abstract Background Clinical screening of first-degree relatives of individuals with hypertrophic cardiomyopathy (HCM) is recommended in international practice guidelines. Recent studies have suggested a lower yield of systematic family screening in gene elusive HCM and that a modified strategy might be appropriate, but it is unknown if these findings can be extrapolated to paediatric relatives. The aim of this study was to determine the yield of clinical screening in first-degree childhood relatives of gene-elusive patients with HCM. Methods Anonymised clinical data were collected from children (≤18 years) referred for first degree family screening between 1994 and 2024 (n=1770). Results 681 consecutive children (from 383 families) were referred for family screening in whom genetic testing had been performed in the index relative (Table). Genetic testing was positive (G+) for disease-causing sarcomeric variants in 401 screening individuals (219 families) and negative (G-) in 280 (164 families). Individuals from G- families were less likely to have a family history of childhood onset disease or sudden death. Over a mean follow up of 5.6 years (+/- 4.1), a diagnosis was made in 50 (12.5%) individuals 38 families (17.3%) from G+ families, compared to 8 (2.9%) individuals 8 families (4.8%) from G- families (p value 0.001). The age and maximal left ventricular wall thickness at the time of diagnosis did not differ between groups. Over a median follow up of 4.9 years (IQR 2.6, 7.1), there was a trend towards a higher rate of ICD implantation (n=18, 36% vs n=1, 12.5%, p value 0.189) and atrial or ventricular arrhythmias (n=6, 12% vs n=0, p=0.301) in the G+ group. Conclusions The diagnostic yield of screening childhood relatives is four-fold higher in genotype positive families, but a childhood diagnosis was still made in 5% of gene-elusive families. The age and phenotype at the time of diagnosis was similar but there was a trend towards a higher rate of disease related complications in genotype positive families. These results support the need for universal screening of first-degree childhood HCM relatives irrespective of genotype status, but further work to determine whether the frequency or timing of screening can be modified is required.Characteristics of screening individuals
Norrish et al. (Sat,) reported a other. Screening childhood relatives of genotype positive HCM families diagnosed 12.5%, four-fold higher than 2.9% in gene-elusive families (p<0.001).