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Congenital heart defects, multiple types, 6(CHTD6)

MedGen UID:
462571
Concept ID:
C3151221
Congenital Abnormality
Synonym: CHTD6
 
Gene (location): GDF1 (19p13.11)
 
Monarch Initiative: MONDO:0013463
OMIM®: 613854

Definition

Multiple types of congenital heart defects are associated with mutation in the GDF1 gene, including tetralogy of fallot (TOF), transposition of the great arteries (TGA), double-outlet right ventricle (DORV), total anomalous pulmonary venous return (TAPVR), pulmonary stenosis or atresia, atrioventricular canal, ventricular septal defect (VSD), and hypoplastic left or right ventricle (Jin et al., 2017). For a discussion of genetic heterogeneity of multiple types of congenital heart defects, see 306955. [from OMIM]

Additional description

From MedlinePlus Genetics
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.

Although 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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/critical-congenital-heart-disease

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.
Double outlet right ventricle
MedGen UID:
41649
Concept ID:
C0013069
Congenital Abnormality
Double outlet right ventricle (DORV) is a type of ventriculoarterial connection in which both great vessels arise entirely or predominantly from the right ventricle.
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.
Right aortic arch
MedGen UID:
48474
Concept ID:
C0035615
Congenital Abnormality
Aorta descends on right instead of on the left.
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.
Transposition of the great arteries
MedGen UID:
21245
Concept ID:
C0040761
Congenital Abnormality
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.
Single ventricle
MedGen UID:
56289
Concept ID:
C0152424
Congenital Abnormality
The presence of only one working lower chamber in the heart, usually with a virtual absence of the ventricular septum and usually present in conjunction with double inlet left or right ventricle.
Complete atrioventricular canal
MedGen UID:
65132
Concept ID:
C0221215
Congenital Abnormality
A congenital heart defect characterized by a specific combination of heart defects with a common atrioventricular valve, primum atrial septal defect and inlet ventricular septal defect.
Pulmonary artery atresia
MedGen UID:
82723
Concept ID:
C0265908
Congenital Abnormality
A congenital anomaly with a narrowing or complete absence of the opening between the right ventricle and the pulmonary artery.
Atrial septal defect, ostium secundum type
MedGen UID:
91034
Concept ID:
C0344724
Congenital Abnormality
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Hypoplastic pulmonary veins
MedGen UID:
373427
Concept ID:
C1970501
Finding
Congenital total pulmonary venous return anomaly
MedGen UID:
1648157
Concept ID:
C4551903
Disease or Syndrome
Total anomalous pulmonary venous return (TAPVR) is a cyanotic form of congenital heart defect in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or one of the venous tributaries (summary by Bleyl et al., 1994).

Professional guidelines

PubMed

Barker PCA, Tatum GH, Campbell MJ, Camitta MGW, Milazzo AS, Hornik CP, French A, Miller SG
Cardiol Young 2018 Nov;28(11):1306-1315. Epub 2018 Aug 6 doi: 10.1017/S104795111800121X. PMID: 30079851Free PMC Article
Cantinotti M, Giordano R, Assanta N, Murzi B, Melo M, Franchi E, Crocetti M, Iervasi G, Kutty S
Clin J Sport Med 2018 Nov;28(6):540-560. doi: 10.1097/JSM.0000000000000474. PMID: 28742603
Colombi M, Dordoni C, Chiarelli N, Ritelli M
Am J Med Genet C Semin Med Genet 2015 Mar;169C(1):6-22. doi: 10.1002/ajmg.c.31429. PMID: 25821090

Recent clinical studies

Etiology

Tambi R, Zehra B, Nandkishore S, Sharafat S, Kader F, Nassir N, Mohamed N, Ahmed A, Abdel Hameid R, Alasrawi S, Brueckner M, Kuebler WM, Chung WK, Alsheikh-Ali A, Di Donato RM, Uddin M, Berdiev BK
Physiol Genomics 2023 Dec 1;55(12):634-646. Epub 2023 Oct 9 doi: 10.1152/physiolgenomics.00070.2023. PMID: 37811720
Negrato CA, Marques PR Júnior, Leite HB, Torigoe CN, Silva BF, Costa K, Kamei JM, Zampa CL, Toni ACRG, Pereira ICGS, Heinzelmann GL, Zajdenverg L
Arch Endocrinol Metab 2022 Nov 17;66(6):908-918. Epub 2022 Oct 3 doi: 10.20945/2359-3997000000521. PMID: 36191262Free PMC Article
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Cantinotti M, Giordano R, Assanta N, Murzi B, Melo M, Franchi E, Crocetti M, Iervasi G, Kutty S
Clin J Sport Med 2018 Nov;28(6):540-560. doi: 10.1097/JSM.0000000000000474. PMID: 28742603
Yuan SM
Cardiol J 2013;20(2):121-4. doi: 10.5603/CJ.2013.0023. PMID: 23558868

Diagnosis

Restrepo CS, Gonzalez TV, Baxi AJ, Saboo SS
Tomography 2022 Jul 27;8(4):1947-1958. doi: 10.3390/tomography8040163. PMID: 36006061Free PMC Article
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
Colombi M, Dordoni C, Chiarelli N, Ritelli M
Am J Med Genet C Semin Med Genet 2015 Mar;169C(1):6-22. doi: 10.1002/ajmg.c.31429. PMID: 25821090
Yuan SM
Cardiol J 2013;20(2):121-4. doi: 10.5603/CJ.2013.0023. PMID: 23558868
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article

Therapy

Adachi I, Peng DM, Hollander SA, Simpson KE, Davies RR, Jacobs JP, VanderPluym CJ, Fynn-Thompson F, Wells DA, Law SP, Amdani S, Cantor R, Koehl D, Kirklin JK, Morales DLS, Rossano JW; Pedimacs Investigators
Ann Thorac Surg 2023 May;115(5):1098-1108. Epub 2022 Nov 17 doi: 10.1016/j.athoracsur.2022.10.042. PMID: 36402175
Quinn BP, Yeh M, Gauvreau K, Ali F, Balzer D, Barry O, Batlivala S, Berman D, Foerster S, Goldstein B, Hainstock M, Holzer R, Janssen D, O'Byrne ML, Shirley L, Trucco S, Whiteside W, Bergersen L
J Am Heart Assoc 2022 Jan 4;11(1):e022832. Epub 2021 Dec 22 doi: 10.1161/JAHA.121.022832. PMID: 34935425Free 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
Gilboa SM, Desrosiers TA, Lawson C, Lupo PJ, Riehle-Colarusso TJ, Stewart PA, van Wijngaarden E, Waters MA, Correa A; National Birth Defects Prevention Study
Occup Environ Med 2012 Sep;69(9):628-35. Epub 2012 Jul 17 doi: 10.1136/oemed-2011-100536. PMID: 22811060Free PMC Article

Prognosis

Tambi R, Zehra B, Nandkishore S, Sharafat S, Kader F, Nassir N, Mohamed N, Ahmed A, Abdel Hameid R, Alasrawi S, Brueckner M, Kuebler WM, Chung WK, Alsheikh-Ali A, Di Donato RM, Uddin M, Berdiev BK
Physiol Genomics 2023 Dec 1;55(12):634-646. Epub 2023 Oct 9 doi: 10.1152/physiolgenomics.00070.2023. PMID: 37811720
Restrepo CS, Gonzalez TV, Baxi AJ, Saboo SS
Tomography 2022 Jul 27;8(4):1947-1958. doi: 10.3390/tomography8040163. PMID: 36006061Free PMC Article
Xie D, Wang H, Liu Z, Fang J, Yang T, Zhou S, Wang A, Qin J, Xiong L
PLoS One 2017;12(6):e0177229. Epub 2017 Jun 7 doi: 10.1371/journal.pone.0177229. PMID: 28591192Free PMC Article
Yuan SM
Cardiol J 2013;20(2):121-4. doi: 10.5603/CJ.2013.0023. PMID: 23558868
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article

Clinical prediction guides

Tambi R, Zehra B, Nandkishore S, Sharafat S, Kader F, Nassir N, Mohamed N, Ahmed A, Abdel Hameid R, Alasrawi S, Brueckner M, Kuebler WM, Chung WK, Alsheikh-Ali A, Di Donato RM, Uddin M, Berdiev BK
Physiol Genomics 2023 Dec 1;55(12):634-646. Epub 2023 Oct 9 doi: 10.1152/physiolgenomics.00070.2023. PMID: 37811720
Brennan Z, Sharaf OM, Treffalls JA, Roa-Vidal N, Weinstein DJ, Bassuk JS, Stukov Y, Peek GJ, Bleiweis MS, Jacobs JP
Cardiol Young 2023 Jul;33(7):1079-1085. Epub 2023 Aug 22 doi: 10.1017/S1047951123001294. PMID: 37605817
Quinn BP, Yeh M, Gauvreau K, Ali F, Balzer D, Barry O, Batlivala S, Berman D, Foerster S, Goldstein B, Hainstock M, Holzer R, Janssen D, O'Byrne ML, Shirley L, Trucco S, Whiteside W, Bergersen L
J Am Heart Assoc 2022 Jan 4;11(1):e022832. Epub 2021 Dec 22 doi: 10.1161/JAHA.121.022832. PMID: 34935425Free PMC Article
Preskorn SH
J Psychiatr Pract 2019 Jul;25(4):290-297. doi: 10.1097/PRA.0000000000000399. PMID: 31291209
Song Y, Higgins H, Guo J, Harrison K, Schultz EN, Hales BJ, Moses EK, Goldblatt J, Pachter N, Zhang G
J Transl Med 2018 Feb 27;16(1):42. doi: 10.1186/s12967-018-1411-0. PMID: 29482591Free PMC Article

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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