Congenital heart disease in Cornelia de Lange syndrome: phenotype and genotype analysis
Kathryn C Chatfield1, Samantha A Schrier, Jennifer Li
1Department of Pediatrics, Section of Pediatric Cardiology, The Children's Hospital of Colorado, Denver, USA.
Insights
Congenital heart disease (CHD) affects many with Cornelia de Lange syndrome (CdLS). Structural heart defects are more common in severe CdLS cases, showing a genotype-phenotype correlation.
Area of Science:
- Genetics
- Cardiology
- Developmental Biology
Background:
- Congenital heart disease (CHD) is a frequent complication in Cornelia de Lange syndrome (CdLS), contributing to significant morbidity and mortality.
- Previous studies report CHD prevalence in CdLS ranging from 14% to 70%.
Purpose of the Study:
- To quantify the occurrence of CHD in a large CdLS cohort.
- To investigate the correlation between CHD, specific gene mutations (NIPBL, SMC1A, SMC3), and CdLS phenotypic severity (mild, moderate, severe).
Main Methods:
- Retrospective chart review of 479 CdLS patients.
- Analysis of cardiac evaluations, genetic testing results, and phenotypic severity data.
- Quantification of CHD presence and types based on mutation status and disease severity.
Main Results:
- 259 out of 479 individuals had documented cardiac findings (structural defects or minor anomalies).
- NIPBL, SMC1A, and SMC3 mutation-positive patients showed similar likelihoods of CHD.
- Structural CHDs were significantly more prevalent in patients with moderate and severe CdLS phenotypes compared to mild phenotypes.
Conclusions:
- CHD is a significant feature in Cornelia de Lange syndrome, with varying prevalence based on disease severity.
- A genotype-phenotype correlation exists, indicating that structural heart defects are more common in individuals with more severe CdLS presentations.
Abstract:
Congenital heart disease (CHD) has been reported to occur in 14-70% of individuals with Cornelia de Lange syndrome (CdLS, OMIM 122470) and accounts for significant morbidity and mortality when present. Charts from a cohort of 479 patients with CdLS were reviewed for cardiac evaluations, gene testing and information to determine phenotypic severity. Two hundred fifty-nine individuals had either documented structural defects or minor cardiac findings. The presence of CHD was then quantified as a function of mutation status and severity of CdLS: mild, moderate, or severe. Different types of CHD were also evaluated by mutation status to assess for any genotype-phenotype correlation. NIPBL, SMC1A, and SMC3 mutation-positive patients were equally likely to have CHD, although the number of SMC1A and SMC3 mutation-positive patients were small in comparison. Structural CHDs were more likely to be present in individuals with moderate and severe CdLS than in the mild phenotype. This study evaluates the trends of CHD seen in the CdLS population and correlates these findings with genotype.
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