Table 1 Cases of TBX4 mutation with neonatal onset pulmonary hypertension or pulmonary hypertension emerging during firsts months of life. CT: computed tomography, ECMO: extracorporeal membrane oxygenation, iNO: inhaled nitric oxide, NA: not applicable, O2: oxygen, PH: pulmonary hypertension
First author, year | Sex | Onset | Gene mutation | Position in protein and amino acids | Inheritance | Others clinical features (0 no;1 toes-pelvis abnormalities, 2 dysmorphic features; 3 neurodevelopmental delay) | Diagnostic approach | Response to medical therapy (+,+/-,-) | Type of drugs used for pulmonary hypertension and cardiovascular dysfunction | Surgical treatment | Age and outcome at follow up | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Nimmakayalu,2010 [7] | F | Birth | microdeletion of17q22q23.2 encompass- ing and TBX4 | NA | De novo | 2 | Echocardiography | NA | tracheostomy, percutaneous gastrostomy | 3 years: improvement of the pulmonary hypertension | |
2 | Szafranski, 2016 [8] | F | Birth | p.E86Q (c.256G > C) | NA | De novo | NA | Echocardiography | NA | none | Neonatal death (first day of life) | |
3 | Suhrie, 2019 [9] | F | Birth | c.524_527del | p.Asn175Thrfs*52 | De novo | 0 | Echocardiography, autopsy | - | iNO, milrinone,inhaled epoprostenol | ECMO | 19 days: death |
4 | Suhrie, 2019 [9] | M | Birth | Del cr 17 (17q23.1-17q23.2) | NA | De novo | 0 | Echocardiography, CT, lung biopsy, cardiac catheterization | - | O2 | tracheostomy, percutaneous gastrostomy | 15 months: chronic respiratory failure |
5 | German, 2019 [10] | M | Birth | Del cr 17 (17q23.2 to 17q23.2) | NA | De novo | 1, 2 | Echocardiography, lung biopsy | - | O2, iNO | ECMO | 10 days: death |
6 | Liu, 2019 [19] | F | Birth | c.1633G > T | p.G545X | AD | NA | Echocardiography | NA | NA | NA | |
7 | Chi, 2019 [20] | NA | Birth | Del TBX gene | NA | NA | NA | Echocardiography, lung biopsy | +/- | iNO, sildenafil, milrinone, epoprostenol | ECMO | 1 month: improvement of PH |
8 | Galambos, 2019 [11] | M | 3 m | Del 17q23.1q23.2 | NA | De novo | 0 | Echocardiography, biopsy | +/- | O2, phosphodiesterase 5 inhibitor | none | 5 months death |
9 | Galambos, 2019 [11] | F | 2 m | Del 17q23.1q23.2 | NA | NA | 1,3 | Echocardiography | + | phosphodiesterase 5 inhibitor, endothelin receptor antagonist | none | 10 years: stable mild PH |
10 | Galambos, 2019 [11] | F | 2 m | Del 17q23.1q23.2 | NA | NA | 1,3 | Echocardiography | + | O2, phosphodiesterase 5 inhibitor, | none | 15 years: stable PH |
11 | Galambos, 2019 [11] | F | 1 m | c.251_delG p. | (Gly84Alafs*4) | De Novo | 3 | Echocardiography | +/- | O2, iNO, phosphodiesterase 5 inhibitor, | none | 8 months: death, PH crisis during surgery (Meckel’s diverticulectomy) |
12 | Galambos, 2019 [11] | F | 1 m | c.1018 C > T p.(Arg340* ) | (Arg340*) | NA | 0 | Echocardiography, biopsy | +/- | O2, phosphodiesterase 5 inhibitor, | none | 4 years: severe lung disease, mild PH |
13 | Galambos, 2019 [11] | M | 1 m | c.1018 C > T p.(Arg340*) | (Arg340*) | NA | 0 | Echocardiography | + | O2, phosphodiesterase 5 inhibitor, endothelin receptor antagonist | none | 3 months no PH, short follow-up |
14 | Karolak, 2019 [12] | M | Birth | c.1198G > A (p.Glu400Lys) | (p.Glu400Lys) | AD | 2 | Echocardiography, chest CT, lung biopsy | - | iNO, O2 | none | 4 months: death |
15 | Flanagan, 2020 [13] | M | Birth | c.401 + 3 A > T | NA | AD | 1 | Cardiac catheterization | +/- | iNO, sildenafil, tadalafil, bosentan | none | 5 years: moderate-severe PH |
16 | Hernandez-Gonzalez,2020 [1] | F | 4 m | TBX4 deletion | NA | De novo | 3 | Echocardiography, CT, cardiac catheterization | + | endothelin receptor antagonist, sildenafil | none | 5 years: resolution of PH |
17 | Hernandez-Gonzalez,2020 [1] | F | 8d | TBX4 deletion | NA | De Novo | 0 | Echocardiography | +/- | sildenafil, systemic prostacyclin | none | 4 months: clinical improvement |
18 | Karolak, 2020 [14] | F | Birth | Del 17q23.1q23.2 | NA | De Novo | NA | Echocardiography, lung biopsy | NA | none | 1 day: death | |
19 | Bölükbasi, 2021 [15] | F | Birth | c.1112dup, SNP rs62069651-C | (p.Pro372Serfs*14) | AD | NA | Autopsy | NA | none | 2 weeks: death | |
20 | Bölükbasi ̧2021 [15] | M | Birth | c.1112dup, SNP rs62069651-C | (p.Pro372Serfs*14) | AD | NA | Autopsy | NA | none | 2 weeks: death | |
21 | Tsoi, 2022 [16] | F | Birth | c.576 C > A | p.(Tyr192* ) | De Novo | NA | Echocardiography, cardiac catheterization, chest CT and lung biopsy | +/- | iNO, sildenafil,bosentan | none | 7 years:restricted lung disease |
22 | Domingo, 2022 [17] | M | Birth | 17q23 microdeletion | NA | NA | NA | Cardiac catheterization, chest CT | +/- | sildenafil, bosentan, intravenous treprostinil, milrinone, iNO, riociguat | none | 21 months: moderate PH |
23 | Flanagan, 2023 [18] | M | Birth | c.401 + 3 A > T | chr17:59543302 | AD | 1 | cardiac catheterization, chest CT | +/- | iNO, sildenafil, tadalafil, bosentan | none | 3 years: chronic respiratory failure |
24 | Flanagan, 2023 [18] | F | Birth | c.401 + 3 A > T | chr17:59543302 | AD | NA | Post mortem lung biopsy | NA | none | 2 days: death |