Authors: Stephanie L Baross, Simon G Williams, Kathryn E Hentges, Bernard D Keavney
Published: 2023-12-19
DOI: 10.1161/circ.148.suppl_1.18657
Source: Full article
Congenital heart disease (CHD) is the most common birth defect affecting around 1% global live births. The aetiology of CHD is poorly understood: while a number genetic loci have already been identified, the majority of cases remain unexplained. Many CHD cases occur with additional abnormalities, or as part of a defined syndrome (eg. Noonan or CHARGE syndromes). The 100,000 Genomes Project conducted whole genome sequencing for patients with a range of rare diseases and cancers in partnership with the UK National Health Service. We analysed clinical and genetic data from the project in 2638 participants with CHD, including both primary CHD cases and secondary cases who have CHD as part of a syndromic presentation but were recruited under other disease categories. Both cohorts are primarily composed of patients with CHD accompanied by additional extra-cardiac abnormalities without a prior diagnosis of a defined syndrome. We found that families recruited as primary CHD cases were significantly less likely to have been classed as “solved cases” (indicating a pathogenic variant has been identified) than phenotypically similar secondary CHD cases (5.4% primary, 16.2% secondary; p = 6.78х