Genetic analyses in a cohort of children with pulmonary hypertension. Issue 4 (1st September 2016)

• Record Type: Journal Article
• Authors: Levy, Marilyne; Eyries, Mélanie; Szezepanski, Isabelle; Ladouceur, Magalie; Nadaud, Sophie; Bonnet, Damien; Soubrier, Florent
• Is Part Of: European respiratory journal. Volume 48:Issue 4(2016)
• Page Start: 1118
• Page End: 1126
• Publication Date: 2016-09-01
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.00211-2016
• Languages: English
• ISSNs: 0903-1936

Abstract

The prevalence of germline mutations in paediatric pulmonary hypertension (PH) is poorly documented. The objective of this study was to determine the mutation frequency in PH genes in a paediatric cohort and describe the clinical characteristics of mutation carriers. The study involved 66 index cases with PH: 35 children with idiopathic pulmonary arterial hypertension (IPAH); five children with familial PAH (FPAH); three children with pulmonary veno-occlusive disease (PVOD); and 23 children with PAH associated with congenital heart disease (APAH-CHD). No mutations were found in the 23 children with APAH-CHD. In the 40 children with IPAH or FPAH, 12 mutations were found: five on BMPR2 ; four on ACVRL1 ; and three on TBX4. In the three PVOD cases, two carried the EIF2AK4 mutation. Mutation carriers had a more severe disease at diagnosis and more aggressive first-line therapy was required. The three patients with PVOD had a very severe disease at diagnosis and required a lung transplantation. The genetic architecture of paediatric PAH is enriched in ACVRL1 and TBX4 mutations compared to adult PAH, but further studies are required to confirm these results. Childhood-onset PAH in children carrying a mutation in one of the genes tested has a more severe presentation at diagnosis but a similar outcome to that observed in non-carriers. Paediatric pulmonary hypertension has a specific genetic architecture http://ow.ly/54yP301hCQi