HOS
MCID: HLT001
MIFTS: 55

Holt-Oram Syndrome (HOS) malady

Cardiovascular, Bone, Fetal categories

Summaries for Holt-Oram Syndrome

Sources:
21Genetics Home Reference, 43NIH Rare Diseases, 47OMIM, 19GeneReviews, 33MalaCards
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NIH Rare Diseases:43 Holt-oram syndrome is a genetic condition characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems. affected individuals have at least one bone abnormality in the wrist, and they may have additional skeletal abnormalities. about 75 percent of individuals with holt-oram syndrome have heart problems, including congenital heart defects and/or cardiac conduction disease, which is an abnormality in the electrical system that coordinates contractions of the heart chambers. holt-oram syndrome is caused by mutations in the tbx5 gene. most cases result from new mutations in this gene and occur in people with no history of the disorder in their family. last updated: 7/19/2011

MalaCards: Holt-Oram Syndrome, also known as heart-hand syndrome, type 1, is related to ventricular septal defect and duane-radial ray syndrome, and has symptoms including pectus excavatum, syndactyly of fingers/interdigital palm and scoliosis. An important gene associated with Holt-Oram Syndrome is TBX5 (T-box 5), and among its related pathways are YAP1- and WWTR1 (TAZ)-stimulated gene expression and Regulation of nuclear SMAD2/3 signaling. The compound zinc have been mentioned in the context of this disorder. Affiliated tissues include lung, heart and prostate, and related mouse phenotypes are craniofacial and limbs/digits/tail.

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:47 142900

GeneReviews summary for hos

Aliases & Classifications for Holt-Oram Syndrome

Sources:
19GeneReviews, 43NIH Rare Diseases, 22GTR, 21Genetics Home Reference, 47OMIM, 45Novoseek, 49Orphanet, 61UMLS, 36MESH via Orphanet, 26ICD10 via Orphanet, 58SNOMED-CT via Orphanet, 62UMLS via Orphanet
See all sources

Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Fetal
Anatomical: Cardiovascular, Bone


Characteristics (Orphanet epidemiological data):

49
holt-oram syndrome:
Inheritance: Autosomal dominant; Age of onset: Neonatal/infancy; Age of death: Any age


Aliases & Descriptions:

holt-oram syndrome 19 43 22 21 47 45 49 61
heart-hand syndrome, type 1 43 21
atriodigital dysplasia 43 21
cardiac-limb syndrome 43 21
hos 21 49
atriodigital dysplasia type 1 49
ventriculo-radial syndrome 21
heart-hand syndrome type 1 49
atrio digital syndrome 43
atrio-digital syndrome 21
heart-hand syndrome 43
holt oram syndrome 45
hearthand syndrome 19


External Ids:

OMIM47 142900
MESH via Orphanet36 C535326
ICD10 via Orphanet26 Q87.2
SNOMED-CT via Orphanet58 19092004
UMLS via Orphanet62 C0265264

Related Diseases for Holt-Oram Syndrome

Sources:
17GeneCards, 18GeneDecks
See all sources

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

(show top 50)    (show all 61)
idRelated DiseaseScoreTop Affiliating Genes
1ventricular septal defect30.6TBX5, NKX2-5
2duane-radial ray syndrome30.4SALL4, TBX5
3polydactyly10.6
4n syndrome10.6
5char syndrome10.5
6hypoplastic left heart syndrome10.4
7arc syndrome10.4
8superior vena cava syndrome10.4
9tbx5-related holt-oram syndrome10.4
10sall4-related holt-oram syndrome10.4
11heart-hand syndrome, slovenian type10.4
12mitral valve prolapse10.3
13osteonecrosis10.3
14malignant hyperthermia10.3
15lymphosarcoma10.3
16patent ductus arteriosus10.3
17pheochromocytoma10.3
18short syndrome10.3
19aortic coarctation10.3
20aortopulmonary window10.3
21atrial septal defect ostium primum10.3
22kuster syndrome10.3
23lung agenesis10.3
24acro-renal-ocular syndrome10.3
25syncope10.3
26multiple ventricular septal defects10.3
27ho kaufman mcalister syndrome10.2
28hyperopia10.2
29tabatznik syndrome10.2
30heart-hand syndrome type 310.2
31brachydactyly10.2
32heart-hand syndrome,spanish type10.2
33diphtheria10.1
34baller-gerold syndrome10.0
35adult syndrome10.0
36brachydactyly type c10.0
37brachydactyly type b10.0
38familial dilated cardiomyopathy10.0
39brachydactyly type d10.0
40ebstein anomaly10.0TBX1
41ulnar-mammary syndrome10.0TBX3, TBX5
42atrial heart septal defect10.0NKX2-5
43atrioventricular septal defect10.0TBX5, NKX2-5
44heart septal defect10.0NKX2-5, TBX5
45velocardiofacial syndrome10.0TBX1
46tetralogy of fallot10.0TBX1, NKX2-5
47digeorge syndrome10.0TBX3, TBX5, TBX1
48congenital heart defect10.0NKX2-5, TBX5, MYH6
49dengue shock syndrome10.0
50mucopolysaccharidosis i10.0

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



Diseases related to holt-oram syndrome

Clinical Features for Holt-Oram Syndrome

Sources:
47OMIM, 49Orphanet
See all sources

Clinical features from OMIM:

142900

Clinical synopsis from OMIM:

142900

Symptoms:

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

Drugs & Therapeutics for Holt-Oram Syndrome

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials, 61UMLS, 41NDF-RT
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Approved drugs:

Search CenterWatch for Holt-Oram Syndrome

Drug clinical trials:

Search ClinicalTrials for Holt-Oram Syndrome

Search NIH Clinical Center for Holt-Oram Syndrome

Search CenterWatch for Holt-Oram Syndrome

Genetic Tests for Holt-Oram Syndrome

Sources:
22GTR
See all sources

Genetic tests related to Holt-Oram Syndrome:

id Genetic test Affiliating Genes
1 Holt-oram Syndrome22

Anatomical Context for Holt-Oram Syndrome

Sources:
33MalaCards
See all sources

MalaCards organs/tissues related to Holt-Oram Syndrome:

33
Lung, Heart, Prostate

Animal Models for Holt-Oram Syndrome or affiliated genes

Sources:
37MGI, 28inGenious Targeting Laboratory
See all sources

Publications for Holt-Oram Syndrome

Sources:
51PubMed
See all sources

Articles related to Holt-Oram Syndrome:

(show top 50)    (show all 171)
idTitleAuthorsYear
1
Unexplained right atrial enlargement may be a sign of Holt-Oram syndrome in the fetus. (24185902)
2013
2
Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. (24011877)
2013
3
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype. (22333898)
2012
4
A Boy with Holt-Oram Syndrome Caused by Novel Mutation c.1304delT in the TBX5 Gene. (22190901)
2011
5
Anaesthetic management of emergency cesarean section in a patient with holt oram syndrome. (21547188)
2010
6
Functional analysis of novel TBX5 T-box mutations associated with Holt-Oram syndrome. (20519243)
2010
7
Caesarean delivery in a parturient with Holt-Oram syndrome and implantable cardioverter defibrillator: anaesthetic considerations. (19037651)
2009
8
Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35. (19648116)
2009
9
Holt-oram syndrome and atrial fibrillation: opening the (T)-box. (18535267)
2008
10
A case of malignant pheochromocytoma with Holt-Oram syndrome. (18250543)
2008
11
Novel TBX5 mutations in patients with Holt-Oram syndrome. (17534187)
2007
12
Holt-Oram syndrome: characterization of a novel mutation]. (16792966)
2006
13
A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. (16332960)
2005
14
TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome. (16183809)
2005
15
Update: PGD and Holt-Oram syndrome. (15940699)
2005
16
Holt-Oram syndrome with hypoplastic left heart syndrome in an African child. (15505648)
2004
17
Preimplantation genetic diagnosis of human congenital heart malformation and Holt-Oram syndrome. (15039979)
2004
18
Holt-Oram syndrome: contribution of prenatal 3-dimensional sonography in an index case. (15292570)
2004
19
Anaesthesia for total hip replacement in a patient with Holt-Oram syndrome. (12703842)
2003
20
Pedigree analysis and descriptive investigation of three classic phenotypes associated with Holt-Oram syndrome. (12698771)
2003
21
Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. (11555635)
2001
22
TBX5 mutation in Chinese patients with Holt-Oram syndrome]. (10932003)
2000
23
Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome. (10842287)
2000
24
Prenatal sonographic diagnosis of Holt-Oram syndrome. (10641008)
2000
25
Holt-Oram syndrome revisited. Two patients in the same family. (10887363)
1999
26
Holt-Oram syndrome. (9771325)
1998
27
The Holt-Oram syndrome: radiological approach. (9260393)
1997
28
Holt-Oram syndrome: a clinical genetic study. (8730285)
1996
29
Holt-Oram syndrome with malformations of renal and cerebral arteries. (8888894)
1996
30
Radial club hand and Holt-Oram syndrome. (7502621)
1995
31
A gene for Holt-Oram syndrome maps to the distal long arm of chromosome 12. (8054983)
1994
32
The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) (8114858)
1994
33
Syncope and sinus arrest associated with the upper limb-cardiovascular (Holt-Oram) syndrome. (7800572)
1994
34
Holt-Oram syndrome in an elderly patient--a case history. (1632574)
1992
35
The Holt-Oram syndrome. (1870097)
1991
36
Variability of the Holt-Oram syndrome in Saudi individuals. (3400729)
1988
37
Concurrence of the Holt-Oram syndrome and the Rokitansky-Kuster-Hauser syndrome. A case report. (3625620)
1987
38
Holt-Oram syndrome: delayed diagnosis. (3446267)
1987
39
Holt-Oram syndrome in a Puerto Rican family--case reports. (3425976)
1987
40
Holt-Oram syndrome in China: a collective review of 18 cases. (3953367)
1986
41
Holt-Oram syndrome--a case report. (3467017)
1986
42
An unusual case of Holt-Oram syndrome. (6519847)
1984
43
Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. (7449488)
1981
44
Upper-limb-cardiovascular syndrome. Two cases of Holt-Oram syndrome. (710983)
1978
45
Holt-Oram syndrome: cardiac limb syndrome. (730328)
1978
46
Association of Holt-Oram syndrome and lymphosarcoma. (4479617)
1974
47
The upper limb-cardiovascular syndrome (Holt-Oram syndrome). A survey and a report of four cases. (4761183)
1973
48
Congenital heart disease and upper extremity defects. A case report (Holt-Oram syndrome). (4266176)
1973
49
The Holt-Oram syndrome: the long and the short of it. (5413182)
1970
50
Holt-Oram syndrome. (6040337)
1967

Genetic Variations for Holt-Oram Syndrome

Sources:
63UniProtKB/Swiss-Prot
See all sources

Genetic disease variations for Holt-Oram Syndrome:

63
id Symbol AA change Variation SNP ID
1TBX5p.Arg237GlnVAR_007456
2TBX5p.Gly80ArgVAR_009701
3TBX5p.Arg237TrpVAR_009702
4TBX5p.Gln49LysVAR_015381
5TBX5p.Ile54ThrVAR_015382

Expression for genes affiliated with Holt-Oram Syndrome

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
Expression patterns in normal tissues for genes affiliated with Holt-Oram Syndrome

Search GEO for disease gene expression data for Holt-Oram Syndrome.

Pathways for genes affiliated with Holt-Oram Syndrome

Sources:
54Reactome, 38NCBI BioSystems Database
See all sources

Pathways related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.6TBX5, KAT2B
29.4NKX2-5, KAT2B
39.2TBX1, TBX5, NKX2-5
49.2NKX2-5, TBX5, MYH6

Compounds for genes affiliated with Holt-Oram Syndrome

Sources:
45Novoseek, 24HMDB
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Compounds related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1zinc45 249.0SRSF2, NKX2-5, KAT2B, SALL4

GO Terms for genes affiliated with Holt-Oram Syndrome

Sources:
16Gene Ontology
See all sources

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

idNameGO IDScoreTop Affiliating Genes
1nucleusGO:0056346.4SRSF2, MYH6, TBX1, TBX5, TBX3, NKX2-5

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

(show all 25)
idNameGO IDScoreTop Affiliating Genes
1forelimb morphogenesisGO:03513610.1TBX5, TBX3
2embryonic forelimb morphogenesisGO:03511510.0TBX3, TBX5
3bundle of His developmentGO:00316610.0TBX5, NKX2-5
4positive regulation of cardioblast differentiationGO:05189110.0TBX5, NKX2-5
5outflow tract morphogenesisGO:0031519.9TBX1, TBX3
6blood vessel developmentGO:0015689.9TBX1, TBX3
7cardiac muscle cell differentiationGO:0550079.9NKX2-5, TBX5
8outflow tract septum morphogenesisGO:0031489.9TBX1, NKX2-5
9ventricular septum morphogenesisGO:0604129.9NKX2-5, TBX3
10pharyngeal system developmentGO:0600379.9NKX2-5, TBX1
11thyroid gland developmentGO:0308789.8TBX1, NKX2-5
12adult heart developmentGO:0075129.8MYH6, NKX2-5
13ventricular septum developmentGO:0032819.8SALL4, TBX5
14heart morphogenesisGO:0030079.8TBX1, NKX2-5
15sarcomere organizationGO:0452149.8MYH6, NKX2-5
16pattern specification processGO:0073899.7TBX1, TBX5
17heart loopingGO:0019479.7TBX3, NKX2-5
18embryonic limb morphogenesisGO:0303269.7TBX5, SALL4
19stem cell maintenanceGO:0198279.6SALL4, TBX3
20BMP signaling pathwayGO:0305099.6MYH6, NKX2-5
21canonical Wnt receptor signaling pathwayGO:0600709.2MYH6, NKX2-5
22positive regulation of transcription, DNA-dependentGO:0458939.2NKX2-5, TBX3, TBX5, TBX1
23positive regulation of cell proliferationGO:0082849.1NKX2-5, TBX3, TBX1
24negative regulation of transcription from RNA polymerase II promoterGO:0001229.0TBX3, NKX2-5, SALL4
25positive regulation of transcription from RNA polymerase II promoterGO:0459448.4SALL4, KAT2B, NKX2-5, TBX5, TBX1

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

idNameGO IDScoreTop Affiliating Genes
1sequence-specific DNA binding transcription factor activityGO:0037008.8TBX1, TBX5, TBX3, NKX2-5
2transcription factor bindingGO:0081348.8KAT2B, NKX2-5, TBX5
3sequence-specific DNA bindingGO:0435658.7TBX1, TBX5, TBX3, NKX2-5

Products for genes affiliated with Holt-Oram Syndrome

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Sources for Holt-Oram Syndrome

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet