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Congenital heart defects, multiple types, 4(CHTD4)

MedGen UID:
862747
Concept ID:
C4014310
Disease or Syndrome
Synonym: CHTD4
 
Gene (location): NR2F2 (15q26.2)
 
Monarch Initiative: MONDO:0014344
OMIM®: 615779

Definition

The multiple types of congenital heart defects observed in CHTD4 include atrial, ventricular, and atrioventricular septal defects, double-outlet right ventricle, tetralogy of Fallot, hypoplastic left heart syndrome, aortic stenosis, and coarctation of the aorta. Intrafamilial variability and incomplete penetrance has been reported (Al Turki et al., 2014; Qiao et al., 2018). Some patients exhibit syndromic features such as developmental delay, congenital diaphragmatic hernia, and severe gastroesophageal reflux (High et al., 2016; Upadia et al., 2018). For a discussion of genetic heterogeneity of multiple types of congenital heart defects, see CHTD1 (306955). [from OMIM]

Clinical features

From HPO
Coarctation of aorta
MedGen UID:
1617
Concept ID:
C0003492
Congenital Abnormality
Coarctation of the aorta is a narrowing or constriction of a segment of the aorta.
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Left ventricular outflow tract obstruction
MedGen UID:
6031
Concept ID:
C0023213
Disease or Syndrome
Left ventricular outflow tract (LVOT) obstruction can occur at the valvular, subvalvular, or supravalvular level. In general, there is an obstruction to forward flow which increases afterload, and if untreated, can result in hypertrophy, dilatation, and eventual failure of the left ventricle.
Tetralogy of Fallot
MedGen UID:
21498
Concept ID:
C0039685
Congenital Abnormality
People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nCritical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.
Hypoplastic left heart syndrome
MedGen UID:
57746
Concept ID:
C0152101
Disease or Syndrome
Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nPeople with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.
Atrioventricular canal defect
MedGen UID:
235591
Concept ID:
C1389016
Anatomical Abnormality
A defect of the atrioventricular septum of the heart.

Professional guidelines

PubMed

Hancock HS, Romano JC, Armstrong A, Yu S, Lowery R, Gelehrter S
World J Pediatr Congenit Heart Surg 2018 Jul;9(4):434-439. doi: 10.1177/2150135118771344. PMID: 29945508
Farias M, Friedman KG, Powell AJ, de Ferranti SD, Marshall AC, Brown DW, Kulik TJ
Pediatrics 2012 Jul;130(1):93-8. Epub 2012 Jun 4 doi: 10.1542/peds.2011-3811. PMID: 22665413Free PMC Article
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Ann Thorac Surg 1992 Apr;53(4):597-602; discussion 602-3. doi: 10.1016/0003-4975(92)90317-w. PMID: 1554267

Recent clinical studies

Etiology

Zeng LF, Tang ZD, Gu J, Wang CQ, Zhang HL
World J Pediatr 2020 Aug;16(4):411-415. Epub 2019 Jul 2 doi: 10.1007/s12519-019-00282-y. PMID: 31267383
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Ou Y, Mai J, Zhuang J, Liu X, Wu Y, Gao X, Nie Z, Qu Y, Chen J, Kielb C, Lauper U, Lin S
Pediatr Res 2016 Apr;79(4):549-58. Epub 2015 Dec 17 doi: 10.1038/pr.2015.264. PMID: 26679154
Yuan SM
Rev Bras Cir Cardiovasc 2014 Oct-Dec;29(4):622-9. doi: 10.5935/1678-9741.20140109. PMID: 25714217Free PMC Article
Bevilacqua A, Willis MS, Bultman SJ
Cardiovasc Pathol 2014 Mar-Apr;23(2):85-91. Epub 2013 Oct 4 doi: 10.1016/j.carpath.2013.09.003. PMID: 24183004Free PMC Article

Diagnosis

Stoll C, Alembik Y, Roth MP
Am J Med Genet A 2022 Jun;188(6):1700-1715. Epub 2022 Feb 18 doi: 10.1002/ajmg.a.62689. PMID: 35179301
Digilio MC, Calcagni G, Gnazzo M, Versacci P, Dentici ML, Capolino R, Sinibaldi L, Baban A, Putotto C, Alfieri P, Unolt M, Lepri FR, Alesi V, Genovese S, Novelli A, Marino B, Dallapiccola B
Am J Med Genet A 2022 Apr;188(4):1149-1159. Epub 2021 Dec 31 doi: 10.1002/ajmg.a.62632. PMID: 34971082
Corsten-Janssen N, Scambler PJ
Am J Med Genet C Semin Med Genet 2017 Dec;175(4):487-495. Epub 2017 Oct 31 doi: 10.1002/ajmg.c.31590. PMID: 29088513
Digilio MC, Gnazzo M, Lepri F, Dentici ML, Pisaneschi E, Baban A, Passarelli C, Capolino R, Angioni A, Novelli A, Marino B, Dallapiccola B
Am J Med Genet A 2017 Nov;173(11):2912-2922. Epub 2017 Sep 8 doi: 10.1002/ajmg.a.38417. PMID: 28884922
Ghosh S, Yarmish G, Godelman A, Haramati LB, Spindola-Franco H
AJR Am J Roentgenol 2009 Oct;193(4):1107-17. doi: 10.2214/AJR.09.2411. PMID: 19770335

Therapy

Di Candia F, Marchetti V, Cirillo F, Di Minno A, Rosano C, Pagano S, Siano MA, Falco M, Assunto A, Boccia G, Magliacane G, Pinna V, De Luca A, Tartaglia M, Di Minno G, Strisciuglio P, Melis D
Orphanet J Rare Dis 2021 Dec 2;16(1):499. doi: 10.1186/s13023-021-02122-7. PMID: 34857025Free PMC Article
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Holzer R, Beekman R, Benson L, Bergersen L, Jayaram N, Jenkins K, Kennedy K, Moore J, Ringel R, Rome J, Vincent R, Martin GR
Cardiol Young 2016 Aug;26(6):1202-12. Epub 2015 Oct 12 doi: 10.1017/S1047951115002218. PMID: 26455737
Isik DU, Celik IH, Kavurt S, Aydemir O, Kibar AE, Bas AY, Demirel N
J Matern Fetal Neonatal Med 2016;29(8):1344-7. Epub 2015 Jun 3 doi: 10.3109/14767058.2015.1048679. PMID: 26037725
Yang L, Tai BC, Khin LW, Quek SC
J Interv Cardiol 2014 Jun;27(3):260-72. Epub 2014 Apr 29 doi: 10.1111/joic.12121. PMID: 24773223

Prognosis

Restrepo CS, Gonzalez TV, Baxi AJ, Saboo SS
Tomography 2022 Jul 27;8(4):1947-1958. doi: 10.3390/tomography8040163. PMID: 36006061Free PMC Article
Zeng LF, Tang ZD, Gu J, Wang CQ, Zhang HL
World J Pediatr 2020 Aug;16(4):411-415. Epub 2019 Jul 2 doi: 10.1007/s12519-019-00282-y. PMID: 31267383
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Verrotti A, Greco M, Varriale G, Tamborino A, Savasta S, Carotenuto M, Elia M, Operto F, Margari L, Belcastro V, Selicorni A, Freri E, Matricardi S, Granata T, Ragona F, Capovilla G, Spalice A, Coppola G, Striano P
Acta Neurol Scand 2018 Dec;138(6):523-530. Epub 2018 Aug 14 doi: 10.1111/ane.13006. PMID: 30109707
Ghosh S, Yarmish G, Godelman A, Haramati LB, Spindola-Franco H
AJR Am J Roentgenol 2009 Oct;193(4):1107-17. doi: 10.2214/AJR.09.2411. PMID: 19770335

Clinical prediction guides

Jacobs ML, Jacobs JP, Thibault D, Hill KD, Anderson BR, Eghtesady P, Karamlou T, Kumar SR, Mayer JE, Mery CM, Nathan M, Overman DM, Pasquali SK, St Louis JD, Shahian D, O'Brien SM
World J Pediatr Congenit Heart Surg 2021 Mar;12(2):246-281. doi: 10.1177/2150135121991528. PMID: 33683997
Zeng LF, Tang ZD, Gu J, Wang CQ, Zhang HL
World J Pediatr 2020 Aug;16(4):411-415. Epub 2019 Jul 2 doi: 10.1007/s12519-019-00282-y. PMID: 31267383
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Digilio MC, Gnazzo M, Lepri F, Dentici ML, Pisaneschi E, Baban A, Passarelli C, Capolino R, Angioni A, Novelli A, Marino B, Dallapiccola B
Am J Med Genet A 2017 Nov;173(11):2912-2922. Epub 2017 Sep 8 doi: 10.1002/ajmg.a.38417. PMID: 28884922
Ghosh S, Yarmish G, Godelman A, Haramati LB, Spindola-Franco H
AJR Am J Roentgenol 2009 Oct;193(4):1107-17. doi: 10.2214/AJR.09.2411. PMID: 19770335

Recent systematic reviews

Restrepo CS, Gonzalez TV, Baxi AJ, Saboo SS
Tomography 2022 Jul 27;8(4):1947-1958. doi: 10.3390/tomography8040163. PMID: 36006061Free PMC Article
Yang L, Tai BC, Khin LW, Quek SC
J Interv Cardiol 2014 Jun;27(3):260-72. Epub 2014 Apr 29 doi: 10.1111/joic.12121. PMID: 24773223

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