Genetics of pulmonary hypertension in the clinic. Issue 5 (September 2017)

• Record Type: Journal Article
• Authors: Girerd, Barbara; Lau, Edmund; Montani, David; Humbert, Marc
• Is Part Of: Current opinion in pulmonary medicine. Volume 23:Issue 5(2017:Sep.)
• Publication Date: 2017-09
• Subjects: genetic counseling -- preimplantation genetic diagnosis -- pulmonary arterial hypertension -- pulmonary capillary hemangiomatosis -- pulmonary veno-occlusive disease; Respiratory organs -- Diseases -- Periodicals; 616.24
• DOI: 10.1097/MCP.0000000000000414
• Languages: English
• ISSNs: 1070-5287

Abstract

Abstract : Purpose of review: Heritable pulmonary arterial hypertension (PAH) is an autosomal dominant disease with incomplete penetrance because of mutations in bone morphogenetic protein receptor-II ( BMPR2 ), activin A receptor type II-like kinase 1, endoglin, caveolin-1, potassium channel subfamily K, member 3, and T-box gene 4 genes. Heritable pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH) is an autosomal recessive disease because of biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene. The 2015 european society of cardiology (ESC) and european respiratory society (ERS) pulmonary hypertension guidelines recommend genetic counselling and testing to adults and children with PAH or PVOD/PCH as well as in adult relatives at risk of carrying a predisposing mutation. Recent findings: In France, genetic counseling and testing are offered to all patients displaying sporadic or familial form of PAH or PVOD/PCH and to their relatives at high risk of carrying a predisposing mutation. Patients with a heritable form of PAH are younger at diagnosis with a worse hemodynamic and a dismal prognosis. Patients with a heritable form of PVOD/PCH are younger at diagnosis with a worse response to specific PAH therapies. A program to detect PAH in an early phase was offered to all asymptomatic BMPR2 mutation carriers, according to the 2015 ESC/ERS guidelines. Finally, preimplantation genetic diagnosis has been performed in families with a history of BMPR2 mutations. Summary: Genetic counseling and testing has to be implemented in pulmonary hypertension centers.