Genetic counselling in pulmonary arterial hypertension: Experience from the French referal centre

Background: Mutations in BMPR2 gene and more rarely in ACVRL1 and ENG genes are detected in patients displaying idiopathic pulmonary arterial hypertension (PAH), pulmonary veno-occlusive disease (PVOD) and in patients with a family history of PAH or PVOD. Aims and objectives: To screen mutations in PAH-predisposing genes in patients from the French Referal Centre and to identify high-risk relatives carrying genetic mutations. Results: Genetic counselling and testing were offered to 434 PAH patients (347 idiopathic and 87 familial) and to 66 PVOD patients (12 with a family history of PVOD). Mutations in PAH predisposing genes were identified in 58 patients with idiopathic PAH (17%) (52 BMPR2 and 6 ACVRL1 mutations) and in 73 PAH patients with a family history of PAH (84%) (69 BMPR2 and 4 ACVRL1 mutations). A BMPR2 mutation was identified in 2 PVOD patients with a family history of the disease (17%) and in only 1 PVOD patient without family history (2%). Genetic screening was offered to 167 asymptomatic relatives of BMPR2/ACVRL1 mutation carriers and a mutation was identified in 60 of them. These subjects, having a 10-20% risk of developing PAH, received clinical screening by echocardiography every 1 to 3 years and when symptoms such as exercise dyspnoea occur. We hypothesize that screening will allow early diagnosis and treatment of the disease and in turn improve patients9 survival. Conclusion: Systematic search of a mutation in PAH predisposing genes allowed us to identified 134 patients carrying a mutation. Half of them had no family history of PAH, suggesting the importance to propose genetic analysis to PAH and PVOD patients with and without family history of the disease.