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. 2022 Sep 9;23(18):10433. doi: 10.3390/ijms231810433

Table 2.

Comparison between published studies analyzing genetics in pediatric pulmonary hypertension. CHD (congenital heart disease); FPAH (familial pulmonary arterial hypertension); HPAH (heritable pulmonary arterial hypertension); IPAH (idiopathic pulmonary arterial hypertension); N/A (not available); PH (pulmonary hypertension); PVOD (pulmonary veno-occlusive disease). * Pathogenic or likely pathogenic variants. ** Only includes heritable cases after genetic analysis (includes familial cases without any significant genetic variant and heritable cases with pathogenic or likely pathogenic variants).

Evaluated Genes Number of Patients PH Groups (IPAH, HPAH, PVOD, CHD, Others) Diagnostic Yield of Genetic Analysis * Results in IPAH/HPAH Results in PVOD Results in CHD-PAH Age at Diagnosis of Mutation Carriers (Mean)
Chida et al., 2012 [18] BMPR2, ACVRL1, SMAD8, BMPR1B 57 46/10/0/0/0 25/54 (46.3%) BMPR2 n = 13/57 (33%)
ALK1 n = 6/57 (13%)
SMAD8 n = 1/57 (1.7%)
BMPR1B n = 2 (3.5%)
NA NA 9.2
Levy et al., 2016 [19] BMPR2, ACVRL1, TBX4, KCNK3, EIF2AK4 42 35/5/3/23 14/42 (33.3%) BMPR2 n = 5/40 (12.5%)
ACVRL1 n = 4/40 (10%)
TBX4 n = 3/40 (7.5%)
EIF2AK4 2/3 (67.7%) 0/23 (0%) 8.3
Zhu et al., 2018 [9] BMPR2, TBX4, ACVRL1, BMPR1B, CAV1, EIF2AK4, ENG, KCNK3, SMAD4, SMAD9 155 130/25 48/155 (31.0%) BMPR2 n = 27/155 (17.7%)
TBX4 n = 12/155 (7.4%)
ACVRL1 n = 3/155 (1.9%), KCNK3 n = 2/155 (1.3%), SMAD9 n = 1/155 (0.6%)
N/A N/A
Haarman et al., 2020 [20] BMPR2, ACVRL1, CAV1, ENG, KCNK3, SMAD9, TBX4, EIF2AK4, VHL, MMACHC, CBLC, ACTA2 70 19/16/5/20/10 19/70 (27.1%) BMPR2 n = 7/35 (20%)
TBX4 n = 7/35 (20%)
ACVRL1 n = 1/35 (2.8%),
PTPN11 n = 2/35 (5.7%)
KCNK3 n = 1/35 (2.8%)
EIF2AK4 2/5 (40.0%) ACTA2 1/20 (5%) 2.8 years TBX4 and14.0 years in BMPR2 carriers
PPHNet Registry. 2021 [6] BMPR2, ACVRL1, SMAD9, CAV1, KCNK3, TBX4, GDF2 40
FPAH
0/40/0/0/0 36/40 heritable cases (90.0%) ** BMPR2 n = 17/40 (43%)
TBX4 n = 6/40 (15%)
ALK/ENG n = 5/40 (5%)
GDF2 n = 2 /40 (5%)
CAV1 n = 1/40 (3%)
KCNK3 n = 1 (3%)
N/A N/A N/A
REHIPED registry (this study) ABCC8, ACVRL1, BMPR1B, BMPR2, CAV1, CBLN2, CPS1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, MMACHC, NOTCH3, SARS2, SMAD1, SMAD4, SMAD5, SMAD9, TBX4, and TOPBP1 98 28/18/8/28/16 44/98 (44.9%) BMPR2 n = 12/50 (24.0%)
TBX4 n = 4/50 (8.0%)
KCNK3 n = 2/50 (4.0%)
ACVRL1 n = 1 (2.0%)
BMPR1B n = 1 (2.0%)
GDF2 n = 1 (2.0%)
EIF2AK4N = 8/8 (100.0%) N = 7/28 (25.0%)
- BMPR2 n = 3
- ENG n = 1
- CPS1 n = 1
- ABCC8/SMAD1 n = 1
- SOX17 n = 1
8.0