Table 3 Clinical and genetic features of high scoring solved and unsolved families
Family code | Score | Proband | Family history | Genetic testing |
|---|---|---|---|---|
Unsolved (ongoing research) | ||||
 VE | 5 | Clinically diagnosed with HCM < 10 years with moderate LVH. SCD < 30 years, with HCM identified as the cause of death at post-mortem | Second-degree relative with confirmed ARVC | Negative WES |
 AMZ | 4 | SCD < 30 years with moderate hypertrophy and dilatation and minor RV fibrosis and fatty infiltration at post-mortem. No clinical diagnosis | Multiple syncopal episodes and RV dilatation in one sibling. Diagnostic type 1 Brugada pattern on ajmaline challenge in multiple relatives. | Negative WGS in the proband and negative WES in the first-, second-, and third-degree relatives |
 CFR | 4 | Multiple syncopal episodes, dyspnoea, and 6-s sinus pause on loop recorder onset < 30 years. Mild LV dilatation on CMR. No clinical diagnosis | SUD during sleep in parent age < 40 years and one sibling with unclassified sinus node disease and PPM | Negative gene panel and WES |
 ABM | 4 | SCA < 30 years, structurally normal heart with atypical ECG changes. ICD implanted for secondary prevention | Children with ECG changes including bradycardia, implanted with PPM | Negative gene panel and WES |
Solved on review | ||||
 EI | 4 | SCA during pregnancy, apical LVH leading to a clinical diagnosis of HCM (ICD implanted). Later decompensated, progressing to severe heart failure. The final diagnosis of ACTN2 cardiomyopathy | Multiple affected relatives with a heterogeneous phenotype ranging from asymptomatic to syncope, heart failure, and SCD | LP variant in ACTN2 identified via research-based linkage analysis |
 RY | 4 | Mild apical LVH and atypical ECG changes, clinically diagnosed with HCM (borderline). The final diagnosis of FHL1 cardiomyopathy, with a neurological review identifying elbow contractures and mild muscular dystrophy | SCD in siblings < 20 years | Negative gene panel, LP variant in FHL1 identified on WES |
 TD | 4 | SCD < 30 years, diagnosed with possible HCM at postmortem investigation. The final diagnosis of SCN5A disease | Family members experienced syncope and multiple relatives subsequently diagnosed with Brugada syndrome | Negative gene panel, LP translocation in SCN5A on WGS |
 CPV | 3 | Elite athlete, presented with SCA < 30 years, but no clinical diagnosis despite extensive investigation. The final diagnosis of DSP cardiomyopathy | No family history of the disease | P truncating variant in DSP identified on a comprehensive cardiac panel |