HOS
MCID: HLT001
MIFTS: 63

Holt-Oram Syndrome (HOS) malady

Cardiovascular diseases, Bone diseases, Fetal diseases categories

Summaries for Holt-Oram Syndrome

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21Genetics Home Reference, 42NIH Rare Diseases, 46OMIM, 19GeneReviews, 32MalaCards
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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 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 thumb hypoplasia/aplasia/absence, fingerlike/triphalangeal thumb and atrioventricular canal. 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 heart, bone 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:46 142900

GeneReviews summary for hos

Aliases & Classifications for Holt-Oram Syndrome

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19GeneReviews, 42NIH Rare Diseases, 22GTR, 21Genetics Home Reference, 46OMIM, 44Novoseek, 48Orphanet, 60UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet, 57SNOMED-CT via Orphanet, 61UMLS via Orphanet
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Classifications:

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


Characteristics (Orphanet epidemiological data):

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


Aliases & Descriptions:

holt-oram syndrome 19 42 22 21 46 44 48 60
heart-hand syndrome, type 1 42 21
atriodigital dysplasia 42 21
cardiac-limb syndrome 42 21
hos 21 48
atriodigital dysplasia type 1 48
ventriculo-radial syndrome 21
heart-hand syndrome type 1 48
atrio digital syndrome 42
atrio-digital syndrome 21
heart-hand syndrome 42
holt oram syndrome 44
hearthand syndrome 19


External Ids:

OMIM46 142900
MESH via Orphanet35 C535326
ICD10 via Orphanet26 Q87.2
SNOMED-CT via Orphanet57 19092004
UMLS via Orphanet61 C0265264

Related Diseases for Holt-Oram Syndrome

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17GeneCards, 18GeneDecks
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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 top 50)    (show all 66)
idRelated DiseaseScoreTop Affiliating Genes
1ventricular septal defect30.6TBX5, NKX2-5
2duane-radial ray syndrome30.4SALL4, TBX5
3tetralogy of fallot30.4TBX1, NKX2-5
4congenital heart defect30.4NKX2-5, TBX5, MYH6
5polydactyly10.6
6osteosarcoma10.5
7hypoplastic left heart syndrome10.4
8tbx5-related holt-oram syndrome10.4
9sall4-related holt-oram syndrome10.4
10heart-hand syndrome, slovenian type10.3
11sarcoma10.3
12mitral valve prolapse10.3
13osteonecrosis10.3
14cerebritis10.3
15double outlet right ventricle10.3
16malignant hyperthermia10.3
17lymphosarcoma10.3
18patent ductus arteriosus10.3
19chromosomal disease10.3
20hypertension10.3
21myopia10.3
22prostate cancer10.3
23prostatitis10.3
24pheochromocytoma10.3
25image syndrome10.3
26tabatznik syndrome10.1
27heart-hand syndrome type 310.1
28mucopolysaccharidosis ii10.1
29mucopolysaccharidosis10.1
30ho kaufman mcalister syndrome10.1
31brachydactyly10.1
32heart-hand syndrome,spanish type10.1
33diphtheria10.1
34baller-gerold syndrome10.0
35adult syndrome10.0
36dilated cardiomyopathy10.0
37heart conduction disease10.0
38ebstein anomaly10.0TBX1
39ulnar-mammary syndrome10.0TBX3, TBX5
40atrial heart septal defect10.0NKX2-5
41atrioventricular septal defect10.0TBX5, NKX2-5
42heart septal defect10.0NKX2-5, TBX5
43velocardiofacial syndrome10.0TBX1
44digeorge syndrome10.0TBX3, TBX5, TBX1
45dengue shock syndrome9.9
46allergic rhinitis9.9
47spinal stenosis9.9
48sialolithiasis9.9
49neuronitis9.9
50intussusception9.9

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



Diseases related to holt-oram syndrome

Clinical Features for Holt-Oram Syndrome

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46OMIM, 48Orphanet
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Clinical features from OMIM:

142900

Clinical synopsis from OMIM:

142900

Symptoms:

48 (show all 24)
  • 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
  • radioulnar synostosis
  • narrow/sloping shoulders
  • ventricular septal defect/interventricular communication
  • 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
  • pectus excavatum

Drugs & Therapeutics for Holt-Oram Syndrome

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-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

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22GTR
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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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32MalaCards
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MalaCards organs/tissues related to Holt-Oram Syndrome:

32
Heart, Bone, Prostate, Lung, Testes

Animal Models for Holt-Oram Syndrome or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Holt-Oram Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053828.5TBX3, NKX2-5, SALL4, TBX1
2MP:00053718.4TBX3, SALL4, TBX5, TBX1
3MP:00028738.2TBX5, KAT2B, TBX1, NKX2-5, TBX3
4MP:00053697.9TBX5, TBX1, MYH6, SRSF2, NKX2-5
5MP:00053807.7TBX3, NKX2-5, KAT2B, SALL4, TBX5, TBX1
6MP:00053857.1SRSF2, SALL4, NKX2-5, TBX3, TBX5, TBX1
7MP:00107686.5TBX1, MYH6, SRSF2, TBX3, NKX2-5, KAT2B

Publications for Holt-Oram Syndrome

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50PubMed
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Articles related to Holt-Oram Syndrome:

(show top 50)    (show all 170)
idTitleAuthorsYear
1
Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. (24011877)
2013
2
Anesthetic implications in Holt-Oram Syndrome. (23545878)
2013
3
Prostate Cancer in a Male with Holt-Oram Syndrome: First Clinical Association of the TBX5 Mutation. (23984174)
2013
4
A Boy with Holt-Oram Syndrome Caused by Novel Mutation c.1304delT in the TBX5 Gene. (22190901)
2011
5
A case report on holt-oram syndrome (heart-hand). (22577452)
2011
6
Holt-Oram syndrome: family affected without TBX5 mutation and without phenotype manifestations in a probable mutation carrier]. (21752519)
2011
7
Holt-Oram syndrome associated with anomalies of the feet. (18351627)
2008
8
Holt-Oram syndrome presenting as agenesis of the left pericardium. (16376438)
2007
9
Anesthesia for cesarean section in a patient with Holt-Oram syndrome. (17126008)
2007
10
Holt-oram syndrome with hemizygous continuation of inferior vena cava. (16551828)
2006
11
Developmental structure-function insights from Tbx5(del/+) mouse model of Holt-Oram syndrome. (16100253)
2005
12
Interventional cardiac catheterization for the coarctation of the aortic arch and patent ductus arteriosus in a 3-day-old neonate with the Holt-Oram syndrome. (15907425)
2005
13
Molecular characterization of a 14q deletion in a boy with features of Holt-Oram syndrome. (15810003)
2005
14
Mayer-von Rokitansky-KA1ster-Hauser syndrome in association with a hitherto undescribed variant of the Holt-Oram syndrome with an aorto-pulmonary window. (15070885)
2004
15
Holt-Oram syndrome with hypoplastic left heart syndrome in an African child. (15505648)
2004
16
TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts. (15221798)
2004
17
Holt-Oram syndrome: contribution of prenatal 3-dimensional sonography in an index case. (15292570)
2004
18
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
19
Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome. (12499378)
2003
20
Anaesthesia for total hip replacement in a patient with Holt-Oram syndrome. (12703842)
2003
21
Current advances in Holt-Oram syndrome. (12436037)
2002
22
Cardiac malformations associated with the Holt-Oram syndrome--report on a family and review of the literature. (12375192)
2002
23
TBX5 mutation in Chinese patients with Holt-Oram syndrome]. (10932003)
2000
24
Bipartite scaphoid with proximal pole osteonecrosis in a patient with Holt-Oram syndrome. (10763739)
2000
25
Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. (10373308)
1999
26
Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. (10077612)
1999
27
Genetical basis of Holt-Oram syndrome]. (10745699)
1999
28
Holt-Oram syndrome. (9771325)
1998
29
Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. (8988164)
1997
30
Holt-Oram syndrome with associated postaxial and central polydactyly. Further evidence for genetic heterogeneity in the Holt-Oram syndrome. (8985738)
1996
31
Residents' corner. Answer to case of the month #33. Holt-Oram syndrome. (7552834)
1995
32
The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) (8114858)
1994
33
Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome. (7820941)
1994
34
Holt-Oram syndrome: postaxial and central polydactyly as variable manifestations in a four generations family. (8110414)
1993
35
Unusual cardiac malformations in Holt-Oram syndrome: report of two cases. (2063682)
1991
36
A case of Holt Oram syndrome. (1894307)
1991
37
Holt-Oram syndrome with polydactyly and ostium primum defect. (2630456)
1989
38
Concurrence of the Holt-Oram syndrome and the Rokitansky-Kuster-Hauser syndrome. A case report. (3625620)
1987
39
The upper limb-cardiovascular syndrome (Holt-Oram syndrome) in a South African family. (4012466)
1985
40
A case of Holt-Oram syndrome severely affecting the skeleton of the upper limbs. (3984053)
1985
41
An unusual case of Holt-Oram syndrome. (6519847)
1984
42
The upper limb-cardiovascular syndrome, (Holt-Oram syndrome). (1277635)
1976
43
Prolapsed mitral valve associated with the Holt-Oram syndrome. (1116403)
1975
44
A family of Holt-Oram syndrome. (1152300)
1975
45
Holt-Oram syndrome associated with combined ostium primum and secundum atrial septal defects: Successful surgical closure. (1199953)
1975
46
J--holt-oram syndrome. (4469991)
1974
47
Association of Holt-Oram syndrome and lymphosarcoma. (4479617)
1974
48
Holt-Oram syndrome. Surgical implications. (5011288)
1972
49
Holt-oram syndrome. (6019507)
1967
50
The syndrome of familial defects of heart and upper extremities (Holt-Oram syndrome). (5940244)
1966

Genetic Variations for Holt-Oram Syndrome

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62UniProtKB/Swiss-Prot
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Genetic disease variations for Holt-Oram Syndrome:

62
id Symbol AA change Variation ID 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

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1BioGPS, 15Gene Expression Omnibus DataSets
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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

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53Reactome, 37NCBI BioSystems Database
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Pathways related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

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

Compounds for genes affiliated with Holt-Oram Syndrome

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

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

GO Terms for genes affiliated with Holt-Oram Syndrome

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16Gene Ontology
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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

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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
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet