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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
Some 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.\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.\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.
Hypoplastic left heart syndrome
MedGen UID:
57746
Concept ID:
C0152101
Disease or Syndrome
Each 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.\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.\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.
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
Masura J, Bordacova L, Tittel P, Berden P, Podnar T
Catheter Cardiovasc Interv 2008 May 1;71(6):843-9. doi: 10.1002/ccd.21540. PMID: 18412082
Chun K, Colombani PM, Dudgeon DL, Haller JA Jr
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

Cai R, Ma X, Zhao X, Xu J, Zhu L, Ku L
J Card Surg 2022 Jul;37(7):2172-2181. Epub 2022 May 4 doi: 10.1111/jocs.16500. PMID: 35508600
Sillesen AS, Vøgg O, Pihl C, Raja AA, Sundberg K, Vedel C, Zingenberg H, Jørgensen FS, Vejlstrup N, Iversen K, Bundgaard H
JAMA 2021 Feb 9;325(6):561-567. doi: 10.1001/jama.2020.27205. PMID: 33560321Free PMC Article
Baird CW, Chávez M, Sleeper LA, Borisuk MJ, Bacha EA, Burchill L, Guleserian K, Ilbawi M, Nguyen K, Razzouk A, Shinkawa T, Lu M, Fuller SM
J Thorac Cardiovasc Surg 2021 Feb;161(2):345-362.e2. Epub 2020 Sep 10 doi: 10.1016/j.jtcvs.2020.06.157. PMID: 33069421
Yuan SM
Rev Bras Cir Cardiovasc 2014 Oct-Dec;29(4):622-9. doi: 10.5935/1678-9741.20140109. PMID: 25714217Free PMC Article
Keckler SJ, St Peter SD, Valusek PA, Tsao K, Snyder CL, Holcomb GW 3rd, Ostlie DJ
Pediatr Surg Int 2007 Apr;23(4):309-13. Epub 2007 Feb 15 doi: 10.1007/s00383-007-1891-0. PMID: 17377826

Diagnosis

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
Sillesen AS, Vøgg O, Pihl C, Raja AA, Sundberg K, Vedel C, Zingenberg H, Jørgensen FS, Vejlstrup N, Iversen K, Bundgaard H
JAMA 2021 Feb 9;325(6):561-567. doi: 10.1001/jama.2020.27205. PMID: 33560321Free PMC Article
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
Spagnoli C, Kugathasan U, Brittain H, Boyd SG
Brain Dev 2015 Aug;37(7):704-13. Epub 2014 Oct 28 doi: 10.1016/j.braindev.2014.10.007. PMID: 25459971
Chun K, Colombani PM, Dudgeon DL, Haller JA Jr
Ann Thorac Surg 1992 Apr;53(4):597-602; discussion 602-3. doi: 10.1016/0003-4975(92)90317-w. PMID: 1554267

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
Baird CW, Chávez M, Sleeper LA, Borisuk MJ, Bacha EA, Burchill L, Guleserian K, Ilbawi M, Nguyen K, Razzouk A, Shinkawa T, Lu M, Fuller SM
J Thorac Cardiovasc Surg 2021 Feb;161(2):345-362.e2. Epub 2020 Sep 10 doi: 10.1016/j.jtcvs.2020.06.157. PMID: 33069421
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Motiwala A, Fatimi SH, Akhtar N, Perveen S, Khan MZ, Atiq M
Thorac Cardiovasc Surg 2011 Aug;59(5):281-6. Epub 2011 Mar 16 doi: 10.1055/s-0030-1250491. PMID: 21412709
Shime N, Kageyama K, Ashida H, Tanaka Y
J Cardiothorac Vasc Anesth 2001 Aug;15(4):463-8. doi: 10.1053/jcan.2001.24983. PMID: 11505351

Prognosis

Cai R, Ma X, Zhao X, Xu J, Zhu L, Ku L
J Card Surg 2022 Jul;37(7):2172-2181. Epub 2022 May 4 doi: 10.1111/jocs.16500. PMID: 35508600
Baird CW, Chávez M, Sleeper LA, Borisuk MJ, Bacha EA, Burchill L, Guleserian K, Ilbawi M, Nguyen K, Razzouk A, Shinkawa T, Lu M, Fuller SM
J Thorac Cardiovasc Surg 2021 Feb;161(2):345-362.e2. Epub 2020 Sep 10 doi: 10.1016/j.jtcvs.2020.06.157. PMID: 33069421
Lazar M, Perelygina L, Martines R, Greer P, Paddock CD, Peltecu G, Lupulescu E, Icenogle J, Zaki SR
EBioMedicine 2016 Jan;3:86-92. Epub 2015 Nov 27 doi: 10.1016/j.ebiom.2015.11.050. PMID: 26870820Free PMC Article
Bostan OM, Cil E, Ercan I
Eur Heart J 2007 Aug;28(16):2001-5. Epub 2007 Jul 10 doi: 10.1093/eurheartj/ehm268. PMID: 17623678
Keckler SJ, St Peter SD, Valusek PA, Tsao K, Snyder CL, Holcomb GW 3rd, Ostlie DJ
Pediatr Surg Int 2007 Apr;23(4):309-13. Epub 2007 Feb 15 doi: 10.1007/s00383-007-1891-0. PMID: 17377826

Clinical prediction guides

Peng DM, Davies RR, Simpson KE, Shugh SB, Morales DLS, Jacobs JP, Butto A, Joong A, Conway J, Schindler K, Griffiths ER, Koehl D, Cantor RS, Kirklin JK, Rossano JW, Adachi I; Pedimacs Investigators
Ann Thorac Surg 2024 Apr;117(4):690-703. Epub 2023 Dec 18 doi: 10.1016/j.athoracsur.2023.11.035. PMID: 38123046
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
Sillesen AS, Vøgg O, Pihl C, Raja AA, Sundberg K, Vedel C, Zingenberg H, Jørgensen FS, Vejlstrup N, Iversen K, Bundgaard H
JAMA 2021 Feb 9;325(6):561-567. doi: 10.1001/jama.2020.27205. PMID: 33560321Free PMC Article
Baird CW, Chávez M, Sleeper LA, Borisuk MJ, Bacha EA, Burchill L, Guleserian K, Ilbawi M, Nguyen K, Razzouk A, Shinkawa T, Lu M, Fuller SM
J Thorac Cardiovasc Surg 2021 Feb;161(2):345-362.e2. Epub 2020 Sep 10 doi: 10.1016/j.jtcvs.2020.06.157. PMID: 33069421
Kardon RE, Cao QL, Masani N, Sugeng L, Supran S, Warner KG, Pandian NG, Marx GR
Circulation 1998 Sep 29;98(13):1307-14. doi: 10.1161/01.cir.98.13.1307. PMID: 9751680

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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