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Heterotaxy, visceral, 5, autosomal(HTX5)

MedGen UID:
501198
Concept ID:
C3495537
Congenital Abnormality
Synonyms: Heterotaxy, visceral, 5; HTX5
 
Gene (location): NODAL (10q22.1)
 
Monarch Initiative: MONDO:0700112
OMIM®: 270100

Definition

Heterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder. For a discussion of genetic heterogeneity of visceral heterotaxy, see HTX1 (306955). [from OMIM]

Additional description

From MedlinePlus Genetics
Depending on the organs involved, signs and symptoms of heterotaxy syndrome can include a bluish appearance of the skin or lips (cyanosis, which is due to a shortage of oxygen), breathing difficulties, an increased risk of infections, and problems with digesting food. The most serious complications are generally caused by critical congenital heart disease, a group of complex heart defects that are present from birth. Biliary atresia, a problem with the bile ducts in the liver, can also cause severe health problems in infancy.

The severity of heterotaxy syndrome varies depending on the specific abnormalities involved. Some affected individuals have only mild health problems related to the condition. At the other end of the spectrum, heterotaxy syndrome can be life-threatening in infancy or childhood, even with treatment.

Heterotaxy syndrome can alter the structure of the heart, including the attachment of the large blood vessels that carry blood to and from the rest of the body. It can also affect the structure of the lungs, such as the number of lobes in each lung and the length of the tubes (called bronchi) that lead from the windpipe to the lungs. In the abdomen, the condition can cause a person to have no spleen (asplenia) or multiple small, poorly functioning spleens (polysplenia). The liver may lie across the middle of the body instead of being in its normal position to the right of the stomach. Some affected individuals also have intestinal malrotation, which is an abnormal twisting of the intestines that occurs in the early stages of development before birth.

In the normal body, most of the organs in the chest and abdomen have a particular location on the right or left side. For example, the heart, spleen, and pancreas are on the left side of the body, and most of the liver is on the right. This normal arrangement of the organs is known as "situs solitus." Rarely, the orientation of the internal organs is completely flipped from right to left, a situation known as "situs inversus." This mirror-image orientation usually does not cause any health problems, unless it occurs as part of a syndrome affecting other parts of the body. Heterotaxy syndrome is an arrangement of internal organs somewhere between situs solitus and situs inversus; this condition is also known as "situs ambiguus." Unlike situs inversus, the abnormal arrangement of organs in heterotaxy syndrome often causes serious health problems.

Heterotaxy syndrome is a condition in which the internal organs are abnormally arranged in the chest and abdomen. The term "heterotaxy" is from the Greek words "heteros," meaning "other than," and "taxis," meaning "arrangement." Individuals with this condition have complex birth defects affecting the heart, lungs, liver, spleen, intestines, and other organs.  https://medlineplus.gov/genetics/condition/heterotaxy-syndrome

Clinical features

From HPO
Ureteral duplication
MedGen UID:
66380
Concept ID:
C0221365
Congenital Abnormality
A developmental anomaly characterized by the presence of two, instead of one, ureter connecting a kidney to the bladder.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Ureteral stenosis
MedGen UID:
105481
Concept ID:
C0521618
Anatomical Abnormality
The presence of a stenotic, i.e., constricted ureter.
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.
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.
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.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
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.
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.
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.
Partial anomalous pulmonary venous return
MedGen UID:
450995
Concept ID:
C0158634
Congenital Abnormality
A form of anomalous pulmonary venous return in which not all pulmonary veins drain abnormally. Partial anomalous pulmonary venous return frequently involves one or both of the veins from one lung.
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.
Double inlet left ventricle
MedGen UID:
488862
Concept ID:
C0344622
Congenital Abnormality
The condition in which both atria are joined to the left ventricle each by its own atrioventricular valve. Usually there is a hypoplastic right ventricle, which may be on the opposite side of the heart as usual.
Ascending tubular aorta aneurysm
MedGen UID:
163631
Concept ID:
C0856747
Anatomical Abnormality
An abnormal localized widening (dilatation) of the tubular part of the ascending aorta.
Atrioventricular canal defect
MedGen UID:
235591
Concept ID:
C1389016
Anatomical Abnormality
A defect of the atrioventricular septum of the heart.
Dextrotransposition of the great arteries
MedGen UID:
758887
Concept ID:
C3531771
Congenital Abnormality
A type of transposition of the great arteries (TGA) in which aorta is in front of and primarily to the right of the pulmonary artery. This is the most common kind of TGA.
Atrial reentry tachycardia
MedGen UID:
868813
Concept ID:
C4023223
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).
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Abdominal situs inversus
MedGen UID:
52359
Concept ID:
C0037221
Congenital Abnormality
A left-right reversal (or mirror reflection) of the anatomical location of the viscera of the abdomen.
Right atrial isomerism
MedGen UID:
465274
Concept ID:
C3178806
Congenital Abnormality
Right atrial isomerism is characterized by bilateral triangular, morphologically right atrial, appendages, both joining the atrial chamber along a broad front with internal terminal crest.
Abdominal situs ambiguus
MedGen UID:
1622585
Concept ID:
C4531036
Anatomical Abnormality
An abnormality in which the abdominal organs are positioned in such a way with respect to each other and the left-right axis as to be not clearly lateralised and thus have neither the usual, or normal (situs solitus), nor the mirror-imaged (situs inversus) arrangements.
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.
Duodenal atresia
MedGen UID:
75602
Concept ID:
C0266174
Congenital Abnormality
A developmental defect resulting in complete obliteration of the duodenal lumen, that is, an abnormal closure of the duodenum.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Absence of the sacrum
MedGen UID:
83373
Concept ID:
C0344490
Congenital Abnormality
Absence (aplasia) of the sacrum.
Bilateral trilobed lung
MedGen UID:
756785
Concept ID:
C3164377
Congenital Abnormality
Both lungs have three lobes. Normally, the left lung has two lobes, whereas the right lung has three lobes.
Asplenia
MedGen UID:
1830315
Concept ID:
C5779621
Anatomical Abnormality
Absence (aplasia) of the spleen.

Recent clinical studies

Etiology

Changlani DK, Kotecha M, Changlani TD, Varghese R, Kumar RS
Heart Lung Circ 2012 Sep;21(9):598-605. Epub 2012 Jun 20 doi: 10.1016/j.hlc.2012.05.739. PMID: 22726404
Yurlov IA, Podzolkov VP, Zelenikin MM, Kovalev DV, Babaev GK, Putiato NA, Zaets SB
Interact Cardiovasc Thorac Surg 2011 Apr;12(4):563-8. Epub 2011 Jan 13 doi: 10.1510/icvts.2010.253567. PMID: 21233261
Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L
J Thorac Cardiovasc Surg 2011 Mar;141(3):637-44, 644.e1-3. Epub 2010 Sep 29 doi: 10.1016/j.jtcvs.2010.07.082. PMID: 20884020Free PMC Article
Prendiville TW, Barton LL, Thompson WR, Fink DL, Holmes KW
Pediatr Cardiol 2010 Oct;31(7):1052-8. Epub 2010 Aug 21 doi: 10.1007/s00246-010-9764-z. PMID: 20730421
Czosek RJ, Haaning A, Ware SM
Pediatr Res 2010 Oct;68(4):275-80. doi: 10.1203/PDR.0b013e3181ee0028. PMID: 20581739Free PMC Article

Diagnosis

Paulussen AD, Steyls A, Vanoevelen J, van Tienen FH, Krapels IP, Claes GR, Chocron S, Velter C, Tan-Sindhunata GM, Lundin C, Valenzuela I, Nagy B, Bache I, Maroun LL, Avela K, Brunner HG, Smeets HJ, Bakkers J, van den Wijngaard A
Eur J Hum Genet 2016 Dec;24(12):1783-1791. Epub 2016 Jul 13 doi: 10.1038/ejhg.2016.91. PMID: 27406248Free PMC Article
D'Alessandro LC, Casey B, Siu VM
Congenit Heart Dis 2013 Mar-Apr;8(2):E36-40. Epub 2011 Dec 16 doi: 10.1111/j.1747-0803.2011.00602.x. PMID: 22171628
Changlani DK, Kotecha M, Changlani TD, Varghese R, Kumar RS
Heart Lung Circ 2012 Sep;21(9):598-605. Epub 2012 Jun 20 doi: 10.1016/j.hlc.2012.05.739. PMID: 22726404
Bedard JE, Haaning AM, Ware SM
PLoS One 2011;6(8):e23755. Epub 2011 Aug 17 doi: 10.1371/journal.pone.0023755. PMID: 21858219Free PMC Article
Williams GD, Feng A
J Cardiothorac Vasc Anesth 2010 Oct;24(5):834-44. Epub 2010 Apr 24 doi: 10.1053/j.jvca.2010.02.012. PMID: 20421166

Therapy

Changlani DK, Kotecha M, Changlani TD, Varghese R, Kumar RS
Heart Lung Circ 2012 Sep;21(9):598-605. Epub 2012 Jun 20 doi: 10.1016/j.hlc.2012.05.739. PMID: 22726404
Yurlov IA, Podzolkov VP, Zelenikin MM, Kovalev DV, Babaev GK, Putiato NA, Zaets SB
Interact Cardiovasc Thorac Surg 2011 Apr;12(4):563-8. Epub 2011 Jan 13 doi: 10.1510/icvts.2010.253567. PMID: 21233261
Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L
J Thorac Cardiovasc Surg 2011 Mar;141(3):637-44, 644.e1-3. Epub 2010 Sep 29 doi: 10.1016/j.jtcvs.2010.07.082. PMID: 20884020Free PMC Article
Williams GD, Feng A
J Cardiothorac Vasc Anesth 2010 Oct;24(5):834-44. Epub 2010 Apr 24 doi: 10.1053/j.jvca.2010.02.012. PMID: 20421166
Naito Y, Aoki M, Matsuo K, Nakajima H, Aotsuka H, Fujiwara T
Eur J Cardiothorac Surg 2010 Jan;37(1):197-203. Epub 2009 Aug 19 doi: 10.1016/j.ejcts.2009.06.055. PMID: 19695897

Prognosis

Changlani DK, Kotecha M, Changlani TD, Varghese R, Kumar RS
Heart Lung Circ 2012 Sep;21(9):598-605. Epub 2012 Jun 20 doi: 10.1016/j.hlc.2012.05.739. PMID: 22726404
Yurlov IA, Podzolkov VP, Zelenikin MM, Kovalev DV, Babaev GK, Putiato NA, Zaets SB
Interact Cardiovasc Thorac Surg 2011 Apr;12(4):563-8. Epub 2011 Jan 13 doi: 10.1510/icvts.2010.253567. PMID: 21233261
Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L
J Thorac Cardiovasc Surg 2011 Mar;141(3):637-44, 644.e1-3. Epub 2010 Sep 29 doi: 10.1016/j.jtcvs.2010.07.082. PMID: 20884020Free PMC Article

Clinical prediction guides

Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L
J Thorac Cardiovasc Surg 2011 Mar;141(3):637-44, 644.e1-3. Epub 2010 Sep 29 doi: 10.1016/j.jtcvs.2010.07.082. PMID: 20884020Free PMC Article
Bianca S, Bartoloni G, Barone C, Barrano B, Boemi G, De Filippo V, Indaco L, Cataliotti A, Ettore G
Congenit Heart Dis 2010 Sep-Oct;5(5):450-3. doi: 10.1111/j.1747-0803.2010.00400.x. PMID: 21087431
Naito Y, Aoki M, Matsuo K, Nakajima H, Aotsuka H, Fujiwara T
Eur J Cardiothorac Surg 2010 Jan;37(1):197-203. Epub 2009 Aug 19 doi: 10.1016/j.ejcts.2009.06.055. PMID: 19695897

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