Benson DW et al. (1999) (2121 Benson DW, Silberbach GM, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest. 1999;104(11):1567-73.) |
TOF and VSD/no thyroid data |
1/7 |
negative |
not reported |
0/50 |
Goldmuntz E et al. (2001) (1515 Goldmuntz E, Geiger E, Benson DW. NKX2.5 mutations in patients with tetralogy of Fallot. Circulation 2001;104(21):2565-8.) |
TOF/no thyroid data |
3/114 (1,3%) |
1 father: ASD |
1 father |
2/43 Africans Americans (2,3%) |
McElhinney DB et al. (2003) (1919 McElhinney DB, Geiger E, Blinder J, Benson DW, Goldmuntz EJ. NKX2.5 mutations in patients with congenital heart disease. Am Coll Cardiol. 2003;42(9):1650-5.) |
7/608 (0,58%)no thyroid data |
TOF Truncus arteriosus Interrupted aortic arch HLHS |
1 1 1 1 |
father: VSD negative negative negative |
not reported negative negative negative |
0/50 randomcontrol Caucasian |
Akcaboy MI et al. (2008) (1616 Akçaboy MI, Cengiz FB, Inceoğlu B, Uçar T, Atalay S, Tutar E, et al. The effect of p.Arg25Cys alteration in NKX2-5 on conotruncal heart anomalies: mutation or polymorphism? Pediatr Cardiol. 2008;29(1):126-9.) |
TOF/no thyroid data |
1/72 (0,69%) |
negative |
father |
2/185 Turkish (0,54%) |
Stallmeyer B et al. (2010) (2020 Stallmeyer B, Fenge H, Nowak-Göttl U, Schulze-Bahr E. Mutational spectrum in the cardiac transcription factor gene NKX2.5 (CSX) associated with congenital heart disease. Clin Genet. 2010;78(6):533-40.) |
HLHS/no thyroid data |
1/121 (0,41%) |
negative |
negative |
0/380 Caucasian |
Perera JL et al. (2010) (44 Perera JL, Johnson NM, Judge DP, Crosson JE. Novel and highly lethal NKX2.5 missense mutation in a family with sudden death and ventricular arrhythmia. Pediatr Cardiol. 2014;35(7):1206-12.) |
TOF/no thyroid data |
1/159 (0,31%) |
sister: VSD |
brother |
0/162 Brazilian |
Rauch R et al. (2010) (2222 Rauch R, Hofbeck M, Zweier C, Koch A, Zink S, Trautmann U, et al. Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot. J Med Genet. 2010;47(5):321-31.) |
TOF/no thyroid data |
2/230 (0,43%) |
negative |
negative |
not tested |
Beffagna G et al. (2013) (2323 Beffagna G, Cecchetto A, Dal Bianco L, Lorenzon A, Angelini A, Padalino M, et al. R25C mutation in the NKX2.5 gene in Italian patients affected with non-syndromic and syndromic congenital heart disease. J Cardiovasc Med (Hagerstown). 2013;14(8):582-6.) |
2/100 (1%) |
CoA, AVSD |
1/100 |
negative |
mother |
0/250 Italian |
|
|
No thyroid defect |
|
|
|
|
|
|
ASD, VSD |
1/100 |
negative |
not tested |
|
|
|
Trisomy 21 |
|
|
|
|
|
|
No thyroid defect |
|
|
|
|
Dentice M et al. (2006) (77 Dentice M, Cordeddu V, Rosica A, Ferrara AM, Santarpia L, Salvatore D, et al. Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol Metab. 2006;91(4):1428-33.) |
2/241 (0,41%) |
Thyroid ectopy TSH 300 mU/L, FT4 5.4 pg/mL No cardiac malformation |
1/241 |
negative |
mother |
1/561 (0,09%) |
|
|
Athyreosis |
1/241 |
negative |
father and brother |
|
|
TSH 419 mU/L, FT4 1.6 pg/mL |
|
|
|
|
|
|
No cardiac malformation |
|
|
|
|
|
|
Bilateral cortex atrophy |
|
|
|
|
|
|
Attention deficit hyperactivity disorder |
|
|
|
|
Khatami M et al. (2017) (88 Khatami M, Heidari MM, Tabesh F, Ordooei M, Salehifar Z. Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with congenital hypothyroidism. J Pediatr Endocrinol Metab. 2017;30(8):857-62.) |
2/65 (1,5%) |
Thyroid hypoplasia TSH 17 mU/L, FT4 1.3 pg/mL No cardiac malformation |
1/65 |
negative |
negative |
0/62 Iranian |
|
Thyroid hypoplasia TSH 21 mU/L, FT4 1.1 pg/mL No cardiac malformation |
1/65 |
negative |
negative |
|
Pulignani S et al. (2018) (2424 Pulignani S, Vecoli C, Borghini A, Foffa I, Ait-Alì L, Andreassi MG. Targeted Next-Generation Sequencing in Patients with Non-syndromic Congenital Heart Disease. Pediatr Cardiol. 2018;39(4):682-9.) |
TOF no thyroid data |
1/17 |
negative |
negative |
not tested |
Alcantara-Ortigoza MA et al. (2021) (2525 Alcántara-Ortigoza MA, Sánchez-Verdiguel I, Fernández-Hernández L, Enríquez-Flores S, González-Núñez A, Hernández-Martínez NL, et al. Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in FOXE1, NKX2-5 and TSHR. Children (Basel). 2021;8(6):457.) |
1 |
Trisomy 21 and normal heart |
3/148 |
negative |
mother |
1/113 Mexican |
|
1 |
Trisomy 21 and perimembranous VSD and PDA |
|
|
father |
|
|
1 |
Trisomy 21 and complete AVSD |
|
|
mother negative, father not tested |
|
In this study |
1 |
Ventricular arrhythmias, no cardiac malformation Thyroid hemiagenesis. TSH 740 mU/L, FT4 0.9 pmol/L Intellectual disability |
1 |
brother: intellectual disability |
mother |
not tested |