HOS
MCID: HLT001
MIFTS: 63

Holt-Oram Syndrome (HOS) malady

Genetic diseases, Rare diseases, Cardiovascular diseases, Bone diseases, Fetal diseases categories
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Summaries for Holt-Oram Syndrome

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NIH Rare Diseases:42 Holt-oram syndrome is a genetic condition characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems. affected people have at least one bone abnormality in the wrist, many of which can be detected only by x-ray. additional skeletal abnormalities may also be present. about 75% of affected people have heart problems, including congenital heart defects and/or cardiac conduction disease (an abnormality in the electrical system that coordinates contractions of the heart chambers). holt-oram syndrome is caused by mutations in the tbx5 gene and is inherited in an autosomal dominant manner. most cases result from new mutations in the gene and occur in people with no family history of the condition. last updated: 9/16/2014

MalaCards based summary: Holt-Oram Syndrome, also known as ventriculo-radial syndrome, is related to ventricular septal defect and duane-radial ray syndrome, and has symptoms including wrist/carpal anomalies, autosomal dominant inheritance and radius anomaly/absence/agenesis/hypoplasia/abnormal radial ray. An important gene associated with Holt-Oram Syndrome is TBX5 (T-box 5), and among its related pathways are Circadian Repression of Expression by REV-ERBA and Heart Development. The compound zinc have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and lung, and related mouse phenotypes are limbs/digits/tail and skeleton.

Genetics Home Reference:21 Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.

Description from OMIM:46 142900

GeneReviews summary for hos

Aliases & Classifications for Holt-Oram Syndrome

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Sources:
19GeneReviews, 42NIH Rare Diseases, 22GTR, 21Genetics Home Reference, 46OMIM, 44Novoseek, 48Orphanet, 62UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Holt-Oram Syndrome, Aliases & Descriptions:

Name: Holt-Oram Syndrome 19 42 22 21 46 44 48 62
Ventriculo-Radial Syndrome 42 21 62
Atriodigital Dysplasia 42 21 62
Cardiac-Limb Syndrome 42 21 62
Hos 42 21 48
Heart-Hand Syndrome, Type 1 42 21
Atrio-Digital Syndrome 21 62
 
Heart-Hand Syndrome 42 62
Atriodigital Dysplasia Type 1 48
Heart-Hand Syndrome Type 1 48
Atrio Digital Syndrome 42
Holt Oram Syndrome 44
Hearthand Syndrome 19
Hos 1 42


Classifications:



Characteristics (Orphanet epidemiological data):

48
holt-oram syndrome:
Inheritance: Autosomal dominant; Age of onset: Neonatal/infancy; Age of death: Any age


External Ids:

OMIM46 142900
MESH via Orphanet35 C535326
ICD10 via Orphanet26 Q87.2
UMLS via Orphanet63 C0265264

Related Diseases for Holt-Oram Syndrome

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Diseases in the Holt-Oram Syndrome family:

Tbx5-Related Holt-Oram Syndrome Sall4-Related Holt-Oram Syndrome

Diseases related to Holt-Oram Syndrome via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 45)
idRelated DiseaseScoreTop Affiliating Genes
1ventricular septal defect30.9NKX2-5, TBX1
2duane-radial ray syndrome30.7SALL4, TBX5
3congenital heart disease30.7NKX2-5, TBX5
4tetralogy of fallot30.6NKX2-5, TBX1
5polydactyly10.6
6hypoplastic left heart syndrome10.5
7tbx5-related holt-oram syndrome10.5
8sall4-related holt-oram syndrome10.5
9heart-hand syndrome, slovenian type10.4
10ebstein anomaly10.4TBX1
11hypertension10.3
12osteonecrosis10.3
13prostate cancer10.3
14pulmonary hypertension10.3
15double outlet right ventricle10.3
16patent ductus arteriosus10.3
17malignant hyperthermia10.3
18lymphosarcoma10.3
19cerebritis10.3
20myopia10.3
21prostatitis10.3
22pheochromocytoma10.3
23aortic coarctation10.3
24aortopulmonary window10.3
25lung agenesis10.3
26acro-renal-ocular syndrome10.3
27syncope10.3
28multiple ventricular septal defects10.3
29atrioventricular block10.3NKX2-5
30ulnar-mammary syndrome10.3TBX5, TBX3
31hypothyroidism10.2MYH6
32tabatznik syndrome10.2
33heart-hand syndrome type 310.2
34heart septal defect10.2NKX2-5, TBX5
35brachydactyly10.2
36heart-hand syndrome,spanish type10.2
37atrioventricular septal defect10.1TBX5, NKX2-5
38allergic rhinitis10.1
39oligodendroglioma10.1
40rhinitis10.1
41velocardiofacial syndrome10.1TBX5, TBX3, TBX1
42dilated cardiomyopathy10.0
43baller-gerold syndrome10.0
44noonan syndrome10.0NKX2-5, MYH6
45atrial heart septal defect10.0MYH6, TBX5, NKX2-5

Graphical network of the top 20 diseases related to Holt-Oram Syndrome:



Diseases related to holt-oram syndrome

Symptoms for Holt-Oram Syndrome

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Symptoms by clinical synopsis from OMIM:

142900

Clinical features from OMIM:

142900

Symptoms:

48 (show all 24)
  • wrist/carpal anomalies
  • autosomal dominant inheritance
  • radius anomaly/absence/agenesis/hypoplasia/abnormal radial ray
  • metacarpal anomalies/archibald's sign
  • thumb hypoplasia/aplasia/absence
  • fingerlike/triphalangeal thumb
  • atrial septal defect/interauricular communication
  • ventricular septal defect/interventricular communication
  • cardiac conduction defect/sinoauricular/heart/auriculoventricular/branch block
  • narrow/sloping shoulders
  • pectus excavatum
  • anomalies of the ribs
  • scoliosis
  • phocomelia
  • scapula structural/position anomaly/congenital elevation/sprengel anomaly
  • humerus anomaly/absence/agenesis/hypoplasia/congenital humerus varus
  • radioulnar synostosis
  • syndactyly of fingers/interdigital palm
  • broad/bifid thumb
  • anomalous pulmonary venous return
  • hypoplastic left heart/ventricle
  • hypoplastic aorta/coarctation/stenosis/anomaly/aortic arch interruption
  • atrioventricular canal
  • patent ductus arteriosus

HPO human phenotypes related to Holt-Oram Syndrome:

(show all 37)
id Description Frequency HPO Source Accession
1 abnormality of the wrist hallmark (90%) HP:0003019
2 abnormality of the metacarpal bones typical (50%) HP:0001163
3 triphalangeal thumb typical (50%) HP:0001199
4 ventricular septal defect typical (50%) HP:0001629
5 defect in the atrial septum typical (50%) HP:0001631
6 aplasia/hypoplasia of the radius typical (50%) HP:0006501
7 aplasia/hypoplasia of the thumb typical (50%) HP:0009601
8 arrhythmia typical (50%) HP:0011675
9 defect in the atrial septum 41.4634% HP:0001631
10 hypoplasia of the radius 37.8049% HP:0002984
11 ventricular septal defect 14.6341% HP:0001629
12 phocomelia 10.9756% HP:0009829
13 abnormality of the sternum occasional (7.5%) HP:0000766
14 patent ductus arteriosus occasional (7.5%) HP:0001643
15 thoracic scoliosis occasional (7.5%) HP:0002943
16 aplasia of the pectoralis major muscle occasional (7.5%) HP:0009751
17 pectus excavatum occasional (7.5%) HP:0000767
18 abnormality of the ribs occasional (7.5%) HP:0000772
19 sprengel anomaly occasional (7.5%) HP:0000912
20 patent ductus arteriosus occasional (7.5%) HP:0001643
21 complete atrioventricular canal defect occasional (7.5%) HP:0001674
22 abnormality of the aorta occasional (7.5%) HP:0001679
23 scoliosis occasional (7.5%) HP:0002650
24 radioulnar synostosis occasional (7.5%) HP:0002974
25 abnormality of the shoulder occasional (7.5%) HP:0003043
26 abnormality of the humerus occasional (7.5%) HP:0003063
27 hypoplastic left heart occasional (7.5%) HP:0004383
28 finger syndactyly occasional (7.5%) HP:0006101
29 phocomelia occasional (7.5%) HP:0009829
30 anomalous pulmonary venous return occasional (7.5%) HP:0010772
31 autosomal dominant inheritance HP:0000006
32 abnormality of the carpal bones HP:0001191
33 triphalangeal thumb HP:0001199
34 abnormality of the vertebrae HP:0003468
35 hypoplastic left heart HP:0004383
36 absent thumb HP:0009777
37 partial duplication of thumb phalanx HP:0009944

Drugs & Therapeutics for Holt-Oram Syndrome

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Drug clinical trials:

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Search NIH Clinical Center for Holt-Oram Syndrome

Genetic Tests for Holt-Oram Syndrome

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Genetic tests related to Holt-Oram Syndrome:

id Genetic test Affiliating Genes
1 Holt-Oram Syndrome22

Anatomical Context for Holt-Oram Syndrome

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MalaCards organs/tissues related to Holt-Oram Syndrome:

32
Heart, Bone, Lung, Prostate, Testes

Animal Models for Holt-Oram Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Holt-Oram Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053718.8TBX1, TBX3, TBX5, SALL4
2MP:00053908.6SALL4, TBX5, TBX3, TBX1
3MP:00053828.6SALL4, NKX2-5, TBX3, TBX1
4MP:00053768.4TBX1, TBX3, TBX5, NKX2-5, MYH6
5MP:00028738.1KAT2B, NKX2-5, TBX5, TBX3, TBX1
6MP:00053698.0MYH6, SRSF2, NKX2-5, TBX5, TBX3, TBX1
7MP:00053807.5KAT2B, SALL4, NKX2-5, TBX5, TBX3, TBX1
8MP:00053857.4TBX1, MYH6, SALL4, SRSF2, NKX2-5, TBX5
9MP:00053787.4KAT2B, SALL4, NKX2-5, TBX3, TBX1
10MP:00107686.6KAT2B, MYH6, SALL4, SRSF2, NKX2-5, TBX5

Publications for Holt-Oram Syndrome

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Articles related to Holt-Oram Syndrome:

(show top 50)    (show all 169)
idTitleAuthorsYear
1
Holt-oram syndrome in adult presenting with heart failure: a rare presentation. (24826304)
2014
2
A New Mutation in the TBX5 Gene in Holt-Oram Syndrome: Two Cases in the Same Family and Prenatal Diagnosis. (24408148)
2014
3
Unexplained right atrial enlargement may be a sign of Holt-Oram syndrome in the fetus. (24185902)
2013
4
Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. (24011877)
2013
5
Holt-oram syndrome associated with double outlet right ventricle: A rare association. (23626447)
2013
6
Tetralogy of Fallot with Holt-Oram syndrome. (22572437)
2012
7
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype. (22333898)
2012
8
A Boy with Holt-Oram Syndrome Caused by Novel Mutation c.1304delT in the TBX5 Gene. (22190901)
2011
9
Holt-Oram syndrome: novel TBX5 mutation and associated anomalous right coronary artery. (21272410)
2011
10
Anaesthetic management of emergency cesarean section in a patient with holt oram syndrome. (21547188)
2010
11
Caesarean delivery in a parturient with Holt-Oram syndrome and implantable cardioverter defibrillator: anaesthetic considerations. (19037651)
2009
12
Prenatal sonographic diagnosis of familial Holt-Oram syndrome associated with type B interrupted aortic arch. (18685167)
2008
13
Picture of the month. Holt-Oram syndrome. (17606836)
2007
14
Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (17366586)
2007
15
Holt-oram syndrome with hemizygous continuation of inferior vena cava. (16551828)
2006
16
Molecular genetic and ocular findings in patients with holt-oram syndrome. (15823919)
2005
17
Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome. (15849237)
2005
18
Holt-Oram syndrome with hypoplastic left heart syndrome in an African child. (15505648)
2004
19
Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy. (12843316)
2003
20
Novel TBX5 mutations and molecular mechanism for Holt-Oram syndrome. (12624158)
2003
21
Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome. (12499378)
2003
22
A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. (11572777)
2001
23
Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. (11555635)
2001
24
Holt-Oram syndrome vs heart-hand syndrome. (10801768)
2000
25
Holt-Oram syndrome. (9771325)
1998
26
Holt-Oram syndrome. (9843474)
1998
27
Variation in severity of cardiac disease in Holt-Oram syndrome. (8911604)
1996
28
A translocation at 12q2 refines the interval containing the Holt-Oram syndrome 1 gene. (8940280)
1996
29
Radial club hand and Holt-Oram syndrome. (7502621)
1995
30
The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) (8114858)
1994
31
The Holt-Oram syndrome. (1870097)
1991
32
Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. (2070544)
1991
33
Unusual cardiac malformations in Holt-Oram syndrome: report of two cases. (2063682)
1991
34
Holt-Oram syndrome. (3100237)
1986
35
The antenatal ultrasonographic detection of the Holt-Oram syndrome. (3898414)
1985
36
Holt-Oram syndrome. (480027)
1979
37
Holt-Oram syndrome: an observation in a father and a son. (438692)
1979
38
An operated case of Holt-Oram syndrome with autosomal dominant inheritance. (1259686)
1976
39
J--holt-oram syndrome. (4469991)
1974
40
Association of Holt-Oram syndrome and lymphosarcoma. (4479617)
1974
41
Holt-Oram syndrome. (4699901)
1973
42
The upper limb-cardiovascular syndrome (Holt-Oram syndrome). A survey and a report of four cases. (4761183)
1973
43
Holt-Oram syndrome (case report). (4659159)
1972
44
Holt-Oram syndrome. Surgical implications. (5011288)
1972
45
Holt Oram syndrome associated with carcinoma. (5559104)
1971
46
The Holt-Oram syndrome: the long and the short of it. (5413182)
1970
47
Associated skeletal and cardiac abnormalities: the Holt-Oram syndrome. (5343603)
1969
48
Holt-Oram syndrome. (6040337)
1967
49
The syndrome of familial defects of heart and upper extremities (Holt-Oram syndrome). (5940244)
1966
50
Holt-Oram syndrome (Upper limb cardiovascular syndrome). (5917980)
1966

Variations for Holt-Oram Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Holt-Oram Syndrome:

64
id Symbol AA change Variation ID SNP ID
1TBX5p.Arg237GlnVAR_007456
2TBX5p.Gly80ArgVAR_009701
3TBX5p.Arg237TrpVAR_009702
4TBX5p.Gln49LysVAR_015381
5TBX5p.Ile54ThrVAR_015382

Clinvar genetic disease variations for Holt-Oram Syndrome:

6
id Gene Name Type Significance SNP ID Assembly Location
1TBX5TBX5, 1491C-Tsingle nucleotide variantPathogenic
2TBX5NM_000192.3(TBX5): c.205G> T (p.Glu69Ter)single nucleotide variantPathogenicrs104894377GRCh37Chr 12, 114839668: 114839668
3TBX5NM_000192.3(TBX5): c.710G> A (p.Arg237Gln)single nucleotide variantPathogenicrs104894378GRCh37Chr 12, 114823326: 114823326
4TBX5NM_000192.3(TBX5): c.238G> A (p.Gly80Arg)single nucleotide variantPathogenicrs104894381GRCh37Chr 12, 114839635: 114839635
5TBX5NM_000192.3(TBX5): c.709C> T (p.Arg237Trp)single nucleotide variantPathogenicrs104894382GRCh37Chr 12, 114823327: 114823327
6TBX5TBX5, 1-BP DEL, 416CdeletionPathogenic
7TBX5NM_000192.3(TBX5): c.145C> A (p.Gln49Lys)single nucleotide variantPathogenicrs104894383GRCh37Chr 12, 114841559: 114841559
8TBX5NM_000192.3(TBX5): c.161T> C (p.Ile54Thr)single nucleotide variantPathogenicrs104894384GRCh37Chr 12, 114839712: 114839712
9TBX5NM_000192.3(TBX5): c.408C> A (p.Tyr136Ter)single nucleotide variantPathogenicrs104894379GRCh37Chr 12, 114836480: 114836480

Expression for genes affiliated with Holt-Oram Syndrome

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Expression patterns in normal tissues for genes affiliated with Holt-Oram Syndrome

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Pathways for genes affiliated with Holt-Oram Syndrome

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Compounds for genes affiliated with Holt-Oram Syndrome

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Sources:
44Novoseek, 24HMDB
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Compounds related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1zinc44 249.0NKX2-5, SRSF2, SALL4, KAT2B

GO Terms for genes affiliated with Holt-Oram Syndrome

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Cellular components related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nucleusGO:0056346.4TBX1, TBX3, TBX5, NKX2-5, SRSF2, SALL4

Biological processes related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

(show all 28)
idNameGO IDScoreTop Affiliating Genes
1forelimb morphogenesisGO:03513610.1TBX5, TBX3
2positive regulation of secondary heart field cardioblast proliferationGO:07251310.1TBX5, TBX1
3embryonic forelimb morphogenesisGO:03511510.0TBX3, TBX5
4bundle of His developmentGO:00316610.0TBX5, NKX2-5
5positive regulation of cardioblast differentiationGO:05189110.0TBX5, NKX2-5
6atrial septum morphogenesisGO:06041310.0TBX5, NKX2-5
7outflow tract morphogenesisGO:0031519.9TBX3, TBX1
8cardiac muscle cell differentiationGO:0550079.9TBX5, NKX2-5
9blood vessel developmentGO:0015689.9TBX1, TBX3
10outflow tract septum morphogenesisGO:0031489.9TBX1, NKX2-5
11pharyngeal system developmentGO:0600379.9NKX2-5, TBX1
12ventricular septum morphogenesisGO:0604129.9NKX2-5, TBX3
13thyroid gland developmentGO:0308789.8TBX1, NKX2-5
14adult heart developmentGO:0075129.8NKX2-5, MYH6
15ventricular septum developmentGO:0032819.8TBX5, SALL4
16heart morphogenesisGO:0030079.8TBX1, NKX2-5
17sarcomere organizationGO:0452149.8NKX2-5, MYH6
18heart loopingGO:0019479.7NKX2-5, TBX3
19pattern specification processGO:0073899.7TBX1, TBX5
20embryonic limb morphogenesisGO:0303269.7TBX5, SALL4
21stem cell maintenanceGO:0198279.7TBX3, SALL4
22BMP signaling pathwayGO:0305099.6NKX2-5, MYH6
23canonical Wnt signaling pathwayGO:0600709.4MYH6, NKX2-5
24positive regulation of cell proliferationGO:0082849.3TBX1, TBX3, NKX2-5
25positive regulation of transcription, DNA-templatedGO:0458939.2TBX1, TBX3, TBX5, NKX2-5
26gene expressionGO:0104678.8TBX5, SRSF2, KAT2B
27negative regulation of transcription from RNA polymerase II promoterGO:0001228.7TBX3, NKX2-5, SALL4
28positive regulation of transcription from RNA polymerase II promoterGO:0459448.1TBX1, TBX5, NKX2-5, SALL4, KAT2B

Molecular functions related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sequence-specific DNA bindingGO:0435658.8NKX2-5, TBX5, TBX3, TBX1
2transcription factor bindingGO:0081348.7KAT2B, NKX2-5, TBX5
3DNA bindingGO:0036778.6SALL4, NKX2-5, TBX5, TBX1
4sequence-specific DNA binding transcription factor activityGO:0037008.5NKX2-5, TBX5, TBX3, TBX1

Products for genes affiliated with Holt-Oram Syndrome

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Sources for Holt-Oram Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet