[Genetic counselling and testing in pulmonary arterial hypertension - A consensus statement on behalf of the International Consortium for Genetic Studies in PAH - French version]. / Conseil génétique et dépistage de l'hypertension artérielle pulmonaire ­ consensus du Consortium international pour les études génétiques dans l'HTAP ­ version française.

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.

[Familial pulmonary veno-occlusive disease with a composite biallelic heterozygous EIF2AK4 mutation]. / Une maladie veino-occlusive pulmonaire familiale avec mutation biallélique hétérozygote composite d'EIF2AK4.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Heritable and sporadic forms have been distinguished. Hypoxemia, profound reduction in the diffusion of carbon monoxide and haemodynamic confirmation of pre-capillary pulmonary hypertension are the major diagnostic criteria. Thoracic CT scanning and a response to pharmaceutical therapy provide additional information to confirm the diagnosis. A 52-year-old patient, three of whose siblings had pulmonary hypertension, was admitted with dyspnoea, malaise and palpitations. Right heart catheterisation confirmed pre-capillary pulmonary hypertension. A search for an EIF2AK4 mutation was carried out, and this showed a composite biallelic heterozygous mutation compatible with the diagnosis of familial PVOD, identical to that showed in one of his brothers. Given the signs of severity of the disease and the diagnosis of PVOD, whose response to pharmaceutical therapy is often poor, the patient was placed on a waiting list for lung transplantation. Despite a similar diagnosis in 3 brothers and follow-up proposed 11 years before the diagnosis, pulmonary hypertension appeared within a few weeks and led immediately to a severe clinical situation. Annual clinical and echocardiographic monitoring had been strongly advised to the patient, but had not allowed diagnosis at a mild or moderate stage of the disease. This clinical case shows that the identification of factors predicting the development of heritable PVOD at a pre-symptomatic stage is an important issue for clinical research.

[Pulmonary veno-occlusive disease]. / La maladie veino-occlusive pulmonaire.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterized by preferential remodelling of pulmonary venules and angioproliferation. PVOD term includes idiopathic, heritable (biallelic mutations of EIF2AK4 gene), drugs and toxins induced (alkylating agents, organic solvents) and connectivite-associated forms (especially systemic-sclerosis associated form). PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation. Lung biopsy is contraindicated in PVOD due to high risk of life-threatening bleeding. A noninvasive diagnostic approach, including oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest, is used to support a diagnosis of PVOD. PVOD prognosis is worse than other forms of PAH. There is no evidence-based medical therapy for PVOD and life-threatening pulmonary edema may occur following PAH targeted therapy in PVOD. Lung transplantation remains the preferred definitive therapy for eligible patients.