Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers.
Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and the activin receptor-like kinase 1 (ALK1) gene have been reported in heritable pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH). However, the relation between clinical characteristics and each gene mutation in IPAH and HPAH is still unclear, especially in childhood. The aim of this study was to determine, in a retrospective study, the influence and clinical outcomes of gene mutations in childhood IPAH and HPAH. Fifty-four patients with IPAH or HPAH whose onset of disease was at <16 years of age were included. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64%, hazard ratio 5.14, p = 0.1205). In conclusion, patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation noncarriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers.
Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.
Ayako
A
Chida
Masaki
M
Shintani
Hisato
H
Yagi
Maya
M
Fujiwara
Yasuko
Y
Kojima
Hiroki
H
Sato
Shinichiro
S
Imamura
Masato
M
Yokozawa
Norio
N
Onodera
Hitoshi
H
Horigome
Tomio
T
Kobayashi
Yoshiho
Y
Hatai
Tomotaka
T
Nakayama
Hiroyuki
H
Fukushima
Mitsunori
M
Nishiyama
Shouzaburo
S
Doi
Yasuo
Y
Ono
Satoshi
S
Yasukouchi
Fukiko
F
Ichida
Kazuto
K
Fujimoto
Shinichi
S
Ohtsuki
Hidetaka
H
Teshima
Tatsuya
T
Kawano
Yuichi
Y
Nomura
Hong
H
Gu
Takahiro
T
Ishiwata
Yoshiyuki
Y
Furutani
Kei
K
Inai
Tsutomu
T
Saji
Rumiko
R
Matsuoka
Shigeaki
S
Nonoyama
Toshio
T
Nakanishi
D030301:Activin Receptors, Type II / Q000235:genetics*; D000293:Adolescent; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; D052006:Bone Morphogenetic Protein Receptors, Type II