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The Yield of Clinical Screening in Pediatric Relatives of Hypertrophic Cardiomyopathy With Negative Genetic Testing
Gabrielle Norrish1, Emma Pascall2, Ella Field1
1Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases, London, United Kingdom; UCL Centre for Paediatric Inherited and Rare Cardiovascular Disease, London, United Kingdom.
Insights
Serial screening of pediatric relatives for hypertrophic cardiomyopathy (HCM) is crucial. Even in genotype-negative families, clinical screening yields diagnoses, supporting universal assessment for children with HCM family history.
Area of Science:
- Cardiology
- Genetics
- Pediatrics
Background:
- Serial clinical screening of first-degree relatives of individuals with hypertrophic cardiomyopathy (HCM) is recommended.
- The yield of screening in adult relatives with genotype-negative disease is lower, suggesting a one-off assessment may suffice.
- It remains unknown if these findings apply to pediatric relatives.
Purpose of the Study:
- To determine the diagnostic yield of clinical screening in pediatric relatives from genotype-negative hypertrophic cardiomyopathy (HCM) families.
- To compare screening yields between genotype-positive (G+) and genotype-negative (G-) pediatric relatives.
- To assess the long-term outcomes of pediatric relatives undergoing HCM screening.
Main Methods:
- Clinical and outcome data were collected from 404 children (≤18 years) from 227 G+ families and 292 children from 170 G- families.
- Follow-up duration was approximately 68.9 months for diagnosis and 8.6 years for clinical events.
- Statistical analysis compared diagnostic yields and clinical outcomes between G+ and G- groups.
Main Results:
- A diagnosis of HCM was made in 9.5% of all pediatric relatives screened, with a higher 5-year cumulative incidence in G+ families (11.1%) versus G- families (4.0%).
- Diagnoses were made in 18.1% of G+ families and 8.2% of G- families.
- While no differences in death or arrhythmic events were observed, symptoms and implantable cardioverter-defibrillator implantation were more frequent in the G+ group.
Conclusions:
- The 5-year diagnostic yield of screening childhood relatives is twofold higher in G+ families.
- A significant proportion (8%) of G- families still received a childhood diagnosis, underscoring the value of screening.
- Universal screening of first-degree childhood relatives with HCM is supported, irrespective of genotype status, though further research on screening frequency and timing is needed.
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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