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Heterotaxy, visceral, 7, autosomal(HTX7)

MedGen UID:
902629
Concept ID:
C4225217
Disease or Syndrome
Synonym: HTX7
 
Gene (location): MMP21 (10q26.2)
 
Monarch Initiative: MONDO:0014762
OMIM®: 616749

Definition

Autosomal visceral heterotaxy-7 is an autosomal recessive developmental disorder characterized by complex congenital heart malformations and/or situs inversus and caused by defects in the normal left-right asymmetric positioning of internal organs. The phenotype is variable (summary by Guimier et al., 2015). For a discussion of the genetic heterogeneity of visceral heterotaxy, see HTX1 (306955). [from OMIM]

Clinical features

From HPO
Dextrocardia
MedGen UID:
4255
Concept ID:
C0011813
Congenital Abnormality
The heart is located in the right hand sided hemithorax. That is, there is a left-right reversal (or "mirror reflection") of the anatomical location of the heart in which the heart is locate on the right side instead of the left.
Abnormal cardiac septum morphology
MedGen UID:
6752
Concept ID:
C0018816
Congenital Abnormality
An anomaly of the intra-atrial or intraventricular septum.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Right aortic arch
MedGen UID:
48474
Concept ID:
C0035615
Congenital Abnormality
Aorta descends on right instead of on the left.
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.
Aortic arch interruption
MedGen UID:
57773
Concept ID:
C0152419
Congenital Abnormality
Non-continuity of the arch of aorta with an atretic point or absent segment.
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.
Pulmonary artery hypoplasia
MedGen UID:
75585
Concept ID:
C0265910
Congenital Abnormality
Underdevelopment of the pulmonary artery.
Mitral atresia disorder
MedGen UID:
91035
Concept ID:
C0344760
Congenital Abnormality
A congenital defect with failure to open of the mitral valve orifice.
Common atrium
MedGen UID:
488886
Concept ID:
C0392482
Congenital Abnormality
Complete absence of the interatrial septum with common atrioventricular valve and two atrioventricular connections.
Atrioventricular canal defect
MedGen UID:
235591
Concept ID:
C1389016
Anatomical Abnormality
A defect of the atrioventricular septum of the heart.
Abnormal aortic valve morphology
MedGen UID:
488999
Concept ID:
C3164445
Anatomical Abnormality
Any abnormality of the aortic valve.
Interrupted inferior vena cava with azygous continuation
MedGen UID:
868827
Concept ID:
C4023237
Congenital Abnormality
Interrupted inferior vena cava with azygous continuation is the result of connection failure between the right subcardinal vein and the right vitelline vein. Consequently, venous blood from the caudal part of the body reaches the heart via the azygous vein and superior vena cava.
Abnormal tricuspid valve morphology
MedGen UID:
871267
Concept ID:
C4025753
Anatomical Abnormality
Any structural anomaly of the tricuspid valve.
Hypoplasia of right ventricle
MedGen UID:
903846
Concept ID:
C4082954
Anatomical Abnormality
Underdevelopment or reduced size of the heart right ventricle, often due to a reduced number of cells.
Situs inversus
MedGen UID:
1642262
Concept ID:
C4551493
Congenital Abnormality
A left-right reversal (or "mirror reflection") of the anatomical location of the major thoracic and abdominal organs.
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).
Heterotaxy
MedGen UID:
75620
Concept ID:
C0266642
Congenital Abnormality
An abnormality in which the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Polysplenia
MedGen UID:
383959
Concept ID:
C1856659
Congenital Abnormality
Polysplenia is a congenital disease manifested by multiple small accessory spleens.
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood.

Recent clinical studies

Etiology

Kapur RP, Cole B, Zhang M, Lin J, Fligner CL
Pediatr Dev Pathol 2013 May-Jun;16(3):191-200. Epub 2013 Feb 25 doi: 10.2350/12-12-1281-OA.1. PMID: 23438674

Diagnosis

Ganapathi M, Buchovecky CM, Cristo F, Ahimaz P, Ruzal-Shapiro C, Wou K, Inácio JM, Iglesias A, Belo JA, Jobanputra V
Cold Spring Harb Mol Case Stud 2022 Dec;8(7) Epub 2022 Dec 28 doi: 10.1101/mcs.a006248. PMID: 36316122Free PMC Article
Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD, Knowles MR, Zariwala MA
Genet Med 2009 Jul;11(7):473-87. doi: 10.1097/GIM.0b013e3181a53562. PMID: 19606528Free PMC Article
Wessels MW, De Graaf BM, Cohen-Overbeek TE, Spitaels SE, de Groot-de Laat LE, Ten Cate FJ, Frohn-Mulder IF, de Krijger R, Bartelings MM, Essed N, Wladimiroff JW, Niermeijer MF, Heutink P, Oostra BA, Dooijes D, Bertoli-Avella AM, Willems PJ
Hum Genet 2008 Jan;122(6):595-603. Epub 2007 Oct 16 doi: 10.1007/s00439-007-0436-x. PMID: 17938964

Therapy

Casey B
Hum Mol Genet 1998;7(10):1565-71. doi: 10.1093/hmg/7.10.1565. PMID: 9735377

Prognosis

Li AH, Hanchard NA, Azamian M, D'Alessandro LCA, Coban-Akdemir Z, Lopez KN, Hall NJ, Dickerson H, Nicosia A, Fernbach S, Boone PM, Gambin T, Karaca E, Gu S, Yuan B, Jhangiani SN, Doddapaneni H, Hu J, Dinh H, Jayaseelan J, Muzny D, Lalani S, Towbin J, Penny D, Fraser C, Martin J, Lupski JR, Gibbs RA, Boerwinkle E, Ware SM, Belmont JW
Eur J Hum Genet 2019 Apr;27(4):563-573. Epub 2019 Jan 8 doi: 10.1038/s41431-018-0307-z. PMID: 30622330Free PMC Article

Clinical prediction guides

Li AH, Hanchard NA, Azamian M, D'Alessandro LCA, Coban-Akdemir Z, Lopez KN, Hall NJ, Dickerson H, Nicosia A, Fernbach S, Boone PM, Gambin T, Karaca E, Gu S, Yuan B, Jhangiani SN, Doddapaneni H, Hu J, Dinh H, Jayaseelan J, Muzny D, Lalani S, Towbin J, Penny D, Fraser C, Martin J, Lupski JR, Gibbs RA, Boerwinkle E, Ware SM, Belmont JW
Eur J Hum Genet 2019 Apr;27(4):563-573. Epub 2019 Jan 8 doi: 10.1038/s41431-018-0307-z. PMID: 30622330Free PMC Article
Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD, Knowles MR, Zariwala MA
Genet Med 2009 Jul;11(7):473-87. doi: 10.1097/GIM.0b013e3181a53562. PMID: 19606528Free PMC Article
Wessels MW, De Graaf BM, Cohen-Overbeek TE, Spitaels SE, de Groot-de Laat LE, Ten Cate FJ, Frohn-Mulder IF, de Krijger R, Bartelings MM, Essed N, Wladimiroff JW, Niermeijer MF, Heutink P, Oostra BA, Dooijes D, Bertoli-Avella AM, Willems PJ
Hum Genet 2008 Jan;122(6):595-603. Epub 2007 Oct 16 doi: 10.1007/s00439-007-0436-x. PMID: 17938964

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