Syndromic conditions in adults with congenital heart disease: prevalence, recognition and clinical impact
M Umei, G P Diller, M Brida, T C Aw, A Hoschtitzky, A Kempny, M A GatzoulisAbstract
Objective
While syndromic conditions are frequently recognised and documented during paediatric care, their identification and documentation in adulthood remain inconsistent and potentially incomplete. This study aimed to assess the recognition of syndromic conditions in adults with congenital heart disease (ACHD). By comparing the clinical identification of syndromic features in adulthood with expectations based on paediatric patterns and known genotype-phenotype associations, we sought to identify potential gaps in diagnostic recognition and highlight opportunities to improve multidisciplinary care and genetic evaluation in ACHD.
Methods
We retrospectively analysed 9,826 adults with congenital heart disease from a tertiary ACHD centre. Syndromic conditions were identified from clinical records and categorised as chromosomal, single-gene, or other syndromes. Clinical characteristics, comorbidities, and CHD complexity were compared between syndromic and non-syndromic patients. Multivariable Cox regression analysis was used to evaluate associations with all-cause mortality.
Results
Among 9,826 patients, 1,070 (10.9%) had a syndromic diagnosis. Marfan syndrome (4.08%) and Down syndrome (3.57%) were the most common, followed by Noonan syndrome (0.74%) and 22q11.2 deletion syndrome (0.69%). Syndromic patients were younger (median age 34 vs 39 years), had higher rates of pulmonary arterial hypertension (15.0% vs 5.9%) and sleep apnoea (7.4% vs 2.8%), but fewer traditional cardiovascular risk factors. Down syndrome clustered with atrioventricular septal defect, whereas 22q11.2 deletion was strongly associated with conotruncal defects. In Tetralogy of Fallot, 4.3% had 22q11.2 deletion, mostly diagnosed in childhood; among patients without a prior diagnosis, most were neither clinically suspected nor genetically tested in adulthood, suggesting under-recognition compared with paediatric cohorts. During follow-up, 199 deaths occurred among the 1,070 syndromic patients. After adjustment for age, sex, NYHA class, and CHD complexity, the presence of a syndromic diagnosis remained independently associated with increased mortality compared with non-syndromic patients (HR 2.05, p<0.001).
Conclusion
More than one in ten adults with congenital heart disease had a syndromic diagnosis, yet key conditions remain under-recognised, particularly 22q11.2 deletion in Tetralogy of Fallot. Closing this diagnostic gap through systematic syndromic assessment in adult CHD care may improve risk stratification, guide tailored surveillance and counselling, and ultimately enhance long-term outcomes.central illustrationFor image description, please refer to the figure legend and surrounding text.