Phenotypes and genotypes in a cohort of children with single-ventricle CHD

CHD is known to be associated with increased risk for neurodevelopmental disorders. The combination of CHD with neurodevelopmental disorders and/or extra-cardiac anomalies increases the chance for an underlying genetic diagnosis. Over the last 15 years, there has been a dramatic increase in the use of broad-scale genetic testing. We sought to determine if neurodevelopmental disorders in children with single-ventricle CHD born prior to the genetic testing revolution are associated with genetic diagnosis.

We identified 74 5-12-year-old patients with single-ventricle CHD post-Fontan procedure. We retrospectively evaluated genetic testing performed and neurodevelopmental status of these patients.

In this cohort, there was an overall higher rate of neurodevelopmental disorders (80%) compared to the literature (50%). More of the younger (5-7-year-old) patients were seen by genetic counsellors compared to the older (8-12-year-old) cohort (46% versus 19% p value = 0.01). In the younger cohort, the average age of initial consultation was 7.7 days compared to 251 days in the older cohort. The overall rate of achieving a molecular diagnosis was 12% and 8% in the younger and older cohorts, respectively; however, the vast majority of did not have broad genetic testing.

The minority of patients in our cohort achieved a genetic diagnosis. Given a large increase in the number of genes associated with monogenic CHD and neurodevelopmental disorders in the last decade, comprehensive testing and consultation with clinical genetics should be considered in this age range, since current testing standards did not exist during their infancy.