Pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is associated with considerable morbidity and even mortality.
Next to environmental risk factors, the investigators believe that there is an important role of genetic predisposition to develop PAH in CHD. There often is a discrepancy between the severity of PAH and the CHD, where it is useful to screen for PAH gene mutations. The investigators hypothesize that the genotype is partly responsible for the phenotypic variability in patients with congenital shunt lesions, where some develop PAH and others do not. If a genetic predisposition for PAH in CHD could be identified, then genetic screening could be a useful additional tool for early detection of patients at risk of pulmonary vascular disease and PAH development, with new opportunities for prevention or early treatment.
Previous diagnosis of secundum atrial septal defect (ASD) or ventricular septal defect (VSD), with or without repair
Development of PAH, defined as mean PAP ≥ 25 mmHg by right heart catheterization, in combination with a pulmonary wedge pressure of ≤ 15 mmHg and a PVR (pulmonary vascular resistance) of > 3 Wood units
Preferably, families with congenital shunt lesions (at least three family members affected with ASD or VSD) will be considered for inclusion
Other congenital heart disease
Mental retardation
Dysmorphic characteristics
Chronic lung disease or total lung capacity < 80% of predicted value
Single group
Genetic testing
Other interventionGenetic testing by DNA sequencing on blood samples after DNA extraction
Presence of pathogenic mutations in PAH or ASD genes
* In a first step, known PAH genes (BMPR2, ALK1 and endoglin) will be screened for mutations. * In a second step, known ASD genes will be screened. * If step 1 and 2 remain negative, exome sequencing will be performed.
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