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Eur Respir J. 2016 Oct;48(4):1118-1126. doi: 10.1183/13993003.00211-2016. Epub 2016 Sep 1.

Genetic analyses in a cohort of children with pulmonary hypertension.

Author information

1
Université Paris Descartes, Sorbonne Paris Cité, Paris, France M3C-Unité Médico-Chirugicale de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France marilyne.levy@ue3c.fr.
2
Genetics Dept, GH Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 1166-ICAN, Paris, France ICAN Institute for Cardiometabolism and Nutrition, Paris, France.
3
Université Paris Descartes, Sorbonne Paris Cité, Paris, France M3C-Unité Médico-Chirugicale de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
4
Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 1166-ICAN, Paris, France ICAN Institute for Cardiometabolism and Nutrition, Paris, France.

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.

PMID:
27587546
DOI:
10.1183/13993003.00211-2016
[Indexed for MEDLINE]
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