MCID: HTR014
MIFTS: 39

Heterotaxy, Visceral, 1, X-Linked

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Heterotaxy, Visceral, 1, X-Linked

MalaCards integrated aliases for Heterotaxy, Visceral, 1, X-Linked:

Name: Heterotaxy, Visceral, 1, X-Linked 53 49 71 69
Htx1 53 49 71
Situs Inversus, Complex Cardiac Defects, and Splenic Defects, X-Linked 53 49
Congenital Heart Defects, Multiple Types, 1, X-Linked 71 69
Congenital Heart Defects, Nonsyndromic, 1, X-Linked 53 13
Dextrocardia with Other Cardiac Malformations 53 71
Heterotaxy, Visceral, X-Linked 49 28
Laterality, X-Linked 53 49
Heterotaxy Syndrome 41 69
Situs Inversus with Complex Cardiac Defects and Splenic Defects X-Linked 71
X-Linked Congenital Heart Defects Nonsyndromic 1 71
X-Linked Congenital Heart Disease Nonsyndromic 1 71
X-Linked Visceral Heterotaxy 1 49
Laterality X-Linked 71
Chtd1 71

Characteristics:

OMIM:

53
Miscellaneous:
highly variable phenotype
heterozygous females may have situs inversus or other midline defects

Inheritance:
x-linked recessive


HPO:

31
heterotaxy, visceral, 1, x-linked:
Onset and clinical course phenotypic variability
Inheritance x-linked inheritance x-linked recessive inheritance


Classifications:



Summaries for Heterotaxy, Visceral, 1, X-Linked

UniProtKB/Swiss-Prot : 71 Congenital heart defects, multiple types, 1, X-linked: A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. Heterotaxy, visceral, 1, X-linked: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in 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. It can been associated with variety of congenital defects including cardiac malformations.

MalaCards based summary : Heterotaxy, Visceral, 1, X-Linked, also known as htx1, is related to heterotaxy and heart disease, and has symptoms including hypertelorism, failure to thrive and cardiomegaly. An important gene associated with Heterotaxy, Visceral, 1, X-Linked is ZIC3 (Zic Family Member 3). Affiliated tissues include heart, spleen and lung.

NIH Rare Diseases : 49 X-linked visceral heterotaxy type 1 is a very rare form of heterotaxy that has only been reported in a few families. Heterotaxy is the right/left transposition of thoracic and/or abdominal organs. This condition is caused by mutations in the ZIC3 gene, is inherited in an X-linked recessive fashion, and is usually seen in males. Physical features include heart abnormalities such as dextrocardia, transposition of great vessels, ventricular septal defect, patent ductus arteriosus, pulmonic stenosis; situs inversus, and missing (asplenia) and/or extra spleens (polysplenia). Affected individuals can also experience abnormalities in the development of the midline of the body, which can cause holoprosencephaly , myelomeningocele, urological anomalies, widely spaced eyes (hypertelorism), cleft palate, and abnormalities of the sacral spine and anus. Heterotaxia with recurrent respiratory infections are called primary ciliary dyskinesia. Last updated: 11/9/2011

Description from OMIM: 306955

Related Diseases for Heterotaxy, Visceral, 1, X-Linked

Diseases related to Heterotaxy, Visceral, 1, X-Linked via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 heterotaxy 32.3 GDF1 ZIC3
2 heart disease 29.2 GDF1 ZIC3
3 visceral heterotaxy 29.2 GDF1 ZIC3
4 cardiac anomalies-heterotaxy syndrome 11.8
5 asplenia, isolated congenital 11.0
6 atrioventricular septal defect 2 11.0
7 pancreas, dorsal, agenesis of 10.9
8 right atrial isomerism 10.9
9 heterotaxy, visceral, 5, autosomal 10.9
10 heterotaxy, visceral, 2, autosomal 10.9
11 heterotaxy, visceral, 3, autosomal 10.9
12 heterotaxy, visceral, 4, autosomal 10.9
13 heterotaxy, visceral, 7, autosomal 10.9
14 heterotaxy, visceral, 8, autosomal 10.9
15 hepatitis 10.0
16 atrioventricular septal defect 9.9
17 conotruncal heart malformations 9.8
18 pulmonary hypertension 9.8
19 atrioventricular block 9.8
20 dextrocardia 9.8
21 aortic coarctation 9.8
22 levocardia 9.8
23 tracheoesophageal fistula with or without esophageal atresia 9.7
24 pulmonary arteriovenous fistulas 9.7
25 budd-chiari syndrome 9.7
26 46,xy gonadal dysgenesis, partial, with minifascicular neuropathy 9.7
27 patent ductus arteriosus 1 9.7
28 cyanosis, transient neonatal 9.7
29 diabetes mellitus 9.7
30 esophageal atresia 9.7
31 arteriovenous malformation 9.7
32 esophagitis 9.7
33 subclavian steal syndrome 9.7
34 pancreatitis 9.7
35 aortopulmonary window 9.7
36 complete atrioventricular canal 9.7
37 gastric duplication cysts 9.7
38 isolated levocardia 9.7
39 pulmonary arteriovenous malformation 9.7
40 pulmonary vein stenosis 9.7
41 dextro-looped transposition of the great arteries 9.7 GDF1 ZIC3
42 tricuspid valve disease 9.7 GDF1 ZIC3
43 transposition of the great arteries 9.6 GDF1 ZIC3

Graphical network of the top 20 diseases related to Heterotaxy, Visceral, 1, X-Linked:



Diseases related to Heterotaxy, Visceral, 1, X-Linked

Symptoms & Phenotypes for Heterotaxy, Visceral, 1, X-Linked

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
hypertelorism

Cardiovascular Heart:
cardiomegaly
atrial septal defect
ventricular septal defect
dextrocardia
pulmonary valve stenosis
more
Abdomen Spleen:
asplenia
polysplenia

Skeletal Spine:
sacral agenesis

Respiratory:
severe respiratory distress at birth

Abdomen Biliary Tract:
extrahepatic biliary atresia

Genitourinary Internal Genitalia Female:
uterine septum

Growth Other:
failure to thrive

Cardiovascular Vascular:
patent ductus arteriosus
transposition of the great arteries
hypoplastic pulmonary arteries

Genitourinary Kidneys:
renal agenesis

Abdomen:
situs inversus viscerum

Respiratory Lung:
lung lobation defects
bilobed right lung

Abdomen Gastroin testinal:
malrotation of the bowel
duodenal obstruction
posteriorly placed anus
rectal stenosis

Skin Nails Hair Skin:
cyanosis due to respiratory insufficiency


Clinical features from OMIM:

306955

Human phenotypes related to Heterotaxy, Visceral, 1, X-Linked:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 HP:0000316
2 failure to thrive 31 HP:0001508
3 cardiomegaly 31 HP:0001640
4 patent ductus arteriosus 31 HP:0001643
5 atrial septal defect 31 HP:0001631
6 ventricular septal defect 31 HP:0001629
7 pulmonic stenosis 31 HP:0001642
8 asplenia 31 HP:0001746
9 dextrocardia 31 HP:0001651
10 transposition of the great arteries 31 HP:0001669
11 mitral atresia 31 HP:0011560
12 renal agenesis 31 HP:0000104
13 abdominal situs inversus 31 HP:0003363
14 polysplenia 31 HP:0001748
15 common atrium 31 HP:0011565
16 single ventricle 31 HP:0001750
17 posteriorly placed anus 31 HP:0012890

Drugs & Therapeutics for Heterotaxy, Visceral, 1, X-Linked

Search Clinical Trials , NIH Clinical Center for Heterotaxy, Visceral, 1, X-Linked

Cochrane evidence based reviews: heterotaxy syndrome

Genetic Tests for Heterotaxy, Visceral, 1, X-Linked

Genetic tests related to Heterotaxy, Visceral, 1, X-Linked:

# Genetic test Affiliating Genes
1 Heterotaxy, Visceral, X-Linked 28 ZIC3

Anatomical Context for Heterotaxy, Visceral, 1, X-Linked

MalaCards organs/tissues related to Heterotaxy, Visceral, 1, X-Linked:

38
Heart, Spleen, Lung, Liver, Eye

Publications for Heterotaxy, Visceral, 1, X-Linked

Articles related to Heterotaxy, Visceral, 1, X-Linked:

(show top 50) (show all 148)
# Title Authors Year
1
Vascular and Splenic Abnormalities in Heterotaxy Syndrome. ( 29289273 )
2018
2
Classifying Heterotaxy Syndrome: Time for a New Approach. ( 29444812 )
2018
3
Heterotaxy syndrome with intestinal malrotation, polysplenia and azygos continuity. ( 29383228 )
2018
4
Pneumococcal vaccination and efficacy in patients with heterotaxy syndrome. ( 28419083 )
2017
5
Noncompaction cardiomyopathy and heterotaxy syndrome. ( 29445263 )
2017
6
Diabetes mellitus due to agenesis of the dorsal pancreas in a patient with heterotaxy syndrome. ( 28690992 )
2017
7
The Missing Link: A Case of Absent Pituitary Infundibulum and Ectopic Neurohypophysis in a Pediatric Patient with Heterotaxy Syndrome. ( 29299107 )
2017
8
Comparing levocardia and dextrocardia in fetuses with heterotaxy syndrome: prenatal features, clinical significance and outcomes. ( 29169330 )
2017
9
Heterotaxy syndrome and associated arrhythmias in pediatric patients. ( 29154821 )
2017
10
Fetal echocardiographic evaluation in cases of heterotaxy syndrome. ( 28594083 )
2017
11
"Twin" Biliary Trees in a Patient with Heterotaxy Syndrome. ( 27504813 )
2016
12
Heterotaxy syndrome with and without spleen: Different infection risk and management. ( 27864025 )
2016
13
Fontan Operation in a Patient with Severe Hypoplastic Right Pulmonary Artery, Single Ventricle, and Heterotaxy Syndrome. ( 27713611 )
2016
14
Predictors of poor outcome among children with heterotaxy syndrome: a retrospective review. ( 27843561 )
2016
15
Outcomes of multistage palliation of infants with functional single ventricle and heterotaxy syndrome. ( 27085618 )
2016
16
When the right (Drug) should be left: Prenatal drug exposure and heterotaxy syndrome. ( 26991659 )
2016
17
Fetal Situs, Isomerism, Heterotaxy Syndrome: Diagnostic Evaluation and Implication for Postnatal Management. ( 27844411 )
2016
18
Pulmonary Hypertension in a Patient With Congenital Heart Defects and Heterotaxy Syndrome. ( 27660582 )
2016
19
Twin Atrioventricular Nodal Reentrant Tachycardia Associated with Heterotaxy Syndrome with Malaligned Atrioventricular Canal Defect and Atrioventricular Discordance. ( 26920197 )
2016
20
The concept of "palliation" in children with heterotaxy syndrome. ( 27085619 )
2016
21
An unusual occurrence: a case of venous thromboembolism in pregnancy associated with heterotaxy syndrome. ( 26052441 )
2015
22
Heterotaxy syndrome with esophageal atresia. ( 25648294 )
2015
23
Low Immunoglobulin M Memory B Cell percentage in patients with Heterotaxy Syndrome Correlates with the Risk of Severe Bacterial Infection. ( 26524717 )
2015
24
Decreased baseline variability on fetal heart rate pattern in a fetus with heterotaxy syndrome. ( 26421346 )
2015
25
Heterotaxy Syndrome: Proceedings From the 10th International PCICS Meeting. ( 26467876 )
2015
26
Comparison of situs ambiguous patterns between heterotaxy syndromes with polysplenia and asplenia. ( 26304785 )
2015
27
Heterotaxy syndrome infants are at risk for early shunt failure after Ladd procedure. ( 25595831 )
2015
28
Heterotaxy syndrome and intestinal rotational anomalies: Impact of the Ladd procedure. ( 25783348 )
2015
29
Contemporary Outcomes of Surgical Repair of Total Anomalous Pulmonary Venous Connection in Patients With Heterotaxy Syndrome. ( 25912749 )
2015
30
Early- and Middle-Term Surgical Outcomes in Patients with Heterotaxy Syndrome. ( 26571485 )
2015
31
Anaesthetic management of a rare case of single ventricle heterotaxy syndrome for emergency caesarean section. ( 26257419 )
2015
32
Duplication and deletion of CFC1 associated with heterotaxy syndrome. ( 25423076 )
2015
33
Orthotopic Heart Transplantation in an Adult Patient with Heterotaxy Syndrome: Surgical Implications. ( 26450654 )
2015
34
Cardiac and Non-Cardiac Abnormalities in Heterotaxy Syndrome. ( 26612104 )
2015
35
Extracardiac anomalies in prenatally diagnosed heterotaxy syndromes. ( 25847110 )
2015
36
Observation versus prophylactic Ladd for asymptomatic intestinal rotational abnormalities in heterotaxy syndrome: A systematic review. ( 26358665 )
2015
37
Racial disparities in heterotaxy syndrome. ( 26333177 )
2015
38
Aortic pseudocoarctation associated with polysplenia/heterotaxy syndrome. ( 25583627 )
2015
39
Heterotaxy syndrome and malrotation: does isomerism influence risk and decision to treat. ( 24888838 )
2014
40
Non-cardiac issues in patients with heterotaxy syndrome. ( 25298693 )
2014
41
Heterotaxy syndrome with malrotation of the gut and interrupted vena cava does not preclude safe procurement of multivisceral graft. ( 24502412 )
2014
42
Percutaneous device occlusion of hepatocardiac venous collateral via left transhepatic access in a patient with heterotaxy syndrome following Fontan procedure. ( 25257146 )
2014
43
Heterotaxy syndromes and abnormal bowel rotation. ( 24419494 )
2014
44
Birth of a healthy boy after PGD for X-linked heterotaxy syndrome. ( 24870704 )
2014
45
Perinatal outcome in fetuses with heterotaxy syndrome and atrioventricular block or bradycardia. ( 24509635 )
2014
46
Antenatal diagnosis of left atrial isomerism and heterotaxy syndrome in fetus with Meckel-Gruber syndrome. ( 24643152 )
2014
47
Coexistence of two distinct fascinating cardiovascular disorders: heterotaxy syndrome with left ventricular non-compaction and vasospastic angina. ( 24768391 )
2014
48
Education and imaging. Gastrointestinal: incidental diagnosis of heterotaxy syndrome in asymptomatic patients. ( 24646425 )
2014
49
Defects in laterality with emphasis on heterotaxy syndromes with asplenia and polysplenia: an autopsy case series at a single institution. ( 24735181 )
2014
50
Management and outcomes of heterotaxy syndrome associated with pulmonary atresia or pulmonary stenosis. ( 24793683 )
2014

Variations for Heterotaxy, Visceral, 1, X-Linked

UniProtKB/Swiss-Prot genetic disease variations for Heterotaxy, Visceral, 1, X-Linked:

71
# Symbol AA change Variation ID SNP ID
1 ZIC3 p.Thr323Met VAR_007753 rs122462165
2 ZIC3 p.Pro217Ala VAR_025632 rs104894963
3 ZIC3 p.Cys253Ser VAR_025633 rs104894961
4 ZIC3 p.His286Arg VAR_025634
5 ZIC3 p.Lys405Glu VAR_025635 rs104894962
6 ZIC3 p.Trp255Gly VAR_042416 rs122463168
7 ZIC3 p.Ser109Cys VAR_071332 rs373628598
8 ZIC3 p.Ala447Gly VAR_071334

ClinVar genetic disease variations for Heterotaxy, Visceral, 1, X-Linked:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 ZIC3 NM_003413.3(ZIC3): c.968C> T (p.Thr323Met) single nucleotide variant Pathogenic rs122462165 GRCh37 Chromosome X, 136649818: 136649818
2 ZIC3 NM_003413.3(ZIC3): c.804C> A (p.Cys268Ter) single nucleotide variant Pathogenic rs122462166 GRCh37 Chromosome X, 136649654: 136649654
3 ZIC3 NM_003413.3(ZIC3): c.1222A> T (p.Lys408Ter) single nucleotide variant Pathogenic rs387906498 GRCh37 Chromosome X, 136651222: 136651222
4 ZIC3 NM_003413.3(ZIC3): c.745C> T (p.Gln249Ter) single nucleotide variant Pathogenic rs104894960 GRCh37 Chromosome X, 136649595: 136649595
5 ZIC3 NM_003413.3(ZIC3): c.758G> C (p.Cys253Ser) single nucleotide variant Pathogenic rs104894961 GRCh37 Chromosome X, 136649608: 136649608
6 ZIC3 NM_003413.3(ZIC3): c.1213A> G (p.Lys405Glu) single nucleotide variant Pathogenic rs104894962 GRCh37 Chromosome X, 136651213: 136651213
7 ZIC3 ZIC3, 2-BP INS, 1507TT insertion Pathogenic
8 ZIC3 NM_003413.3(ZIC3): c.763T> G (p.Trp255Gly) single nucleotide variant Pathogenic rs122463168 GRCh37 Chromosome X, 136649613: 136649613
9 GDF1 NM_001492.5(GDF1): c.681C> A (p.Cys227Ter) single nucleotide variant Pathogenic rs121434422 GRCh37 Chromosome 19, 18979844: 18979844
10 ZIC3 NM_003413.3(ZIC3): c.(?_-1)_(*1_?)del deletion Pathogenic
11 ZIC3 NM_003413.3(ZIC3): c.764G> C (p.Trp255Ser) single nucleotide variant Likely pathogenic rs886041111 GRCh38 Chromosome X, 137567455: 137567455
12 ZIC3 NM_003413.3(ZIC3): c.1025delC (p.Ser342Leufs) deletion Pathogenic rs886042663 GRCh37 Chromosome X, 136649875: 136649875
13 ZIC3 NM_003413.3(ZIC3): c.476_479delACTT (p.Tyr159Cysfs) deletion Pathogenic GRCh38 Chromosome X, 137567167: 137567170

Expression for Heterotaxy, Visceral, 1, X-Linked

Search GEO for disease gene expression data for Heterotaxy, Visceral, 1, X-Linked.

Pathways for Heterotaxy, Visceral, 1, X-Linked

GO Terms for Heterotaxy, Visceral, 1, X-Linked

Sources for Heterotaxy, Visceral, 1, X-Linked

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