Pediatric forms of PAH can be also linked to ACVRL1 mutations responsible for hereditary hemorrhagic telangiectasia, and the disease may be unapparent at the time of PAH occurrence in childhood; some authors have identified families with an unrecognized hereditary hemorrhagic telangiectasia causing PAH in childhood.This difference might also be due to the criteria used for defining familial forms.Moreover, the uncertainty about the pathological significance of the variants in TBX4 and KCNK3 hampers any robust interpretation. Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, et al. Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons. Some lessons can be drawn from this article, and from other recently published studies. Fujiwara M, Yagi H, Matsuoka R, Akimoto K, Furutani M, Imamura S, et al. A novel channelopathy in pulmonary arterial hypertension. The proportion of acute responders in i PAH patients in this study, 39% in the i PAH population, is in striking contrast with the proportion of around 12% reported in the literature. Sitbon O, Humbert M, Jais X, Ioos V, Hamid AM, Provencher S, et al. Absence of influence of gender and BMPR2 mutation type on clinical phenotypes of pulmonary arterial hypertension. This difference might be due to criteria used for defining acute response, which should be clarified to determine whether there is another reason for this difference. Evans JD, Girerd B, Montani D, Wang XJ, Galiè N, Austin ED, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. To identify the causative gene, it is important to perform, when possible, a complete genetic investigation in PAH patients, including BMPR2, KCNK3, TBX4, and ACVRL1 genes, the 2 last genes being more important in pediatric PAH, as already mentioned. Girerd B, Montani D, Jaïs X, Eyries M, Yaici A, Sztrymf B, et al. Implications of mutations of activin receptor-like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension. Moreover, wide mutation screening can be achieved by the design of large panels for sequencing covering all the genes involved in PAH, including those rarely involved, such as caveolin-1, and Smad9. Girerd B, Coulet F, Jaïs X, Eyries M, Van der Bruggen C, De Man F, et al. Genetic counselling in a national referral centre for pulmonary hypertension.
The baseline clinical and hemodynamic status and the survival rate of the PAH patients included in this study were carefully collected and analyzed in relation to the genotypes of the patients and the type of PAH, idiopathic PAH (i PAH) vs hereditary PAH.
Hemodynamic parameters in BMPR2 mutation carriers have a tendency to be more severe than in noncarriers, as observed by Evans et al. Soubrier F, Chung WK, Machado R, Grunig E, Aldred M, Geraci M, et al. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.