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 radioulnar synostosis, syndactyly of fingers/interdigital palm and broad/bifid thumb. 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 testes, 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)
  • 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
  • humerus anomaly/absence/agenesis/hypoplasia/congenital humerus varus
  • scapula structural/position anomaly/congenital elevation/sprengel anomaly
  • phocomelia
  • 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
  • wrist/carpal anomalies

Drugs & Therapeutics for Holt-Oram Syndrome

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Sources:
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, Testes, Prostate, Lung

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:00053828.5TBX1, TBX3, NKX2-5, SALL4
2MP:00053718.4SALL4, TBX3, TBX5, TBX1
3MP:00028738.2KAT2B, NKX2-5, TBX3, TBX5, TBX1
4MP:00053697.9NKX2-5, TBX5, TBX1, MYH6, SRSF2
5MP:00053807.7SALL4, KAT2B, NKX2-5, TBX3, TBX5, TBX1
6MP:00053857.1SRSF2, SALL4, NKX2-5, TBX3, TBX5, TBX1
7MP:00107686.5SALL4, KAT2B, NKX2-5, TBX3, TBX5, TBX1

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
Unexplained right atrial enlargement may be a sign of Holt-Oram syndrome in the fetus. (24185902)
2013
2
Holt-oram syndrome associated with double outlet right ventricle: A rare association. (23626447)
2013
3
Tetralogy of Fallot with Holt-Oram syndrome. (22572437)
2012
4
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype. (22333898)
2012
5
Caesarean delivery in a parturient with Holt-Oram syndrome and implantable cardioverter defibrillator: anaesthetic considerations. (19037651)
2009
6
Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35. (19648116)
2009
7
Prenatal diagnosis of Holt-Oram syndrome: role of 3-D ultrasonography. (19243417)
2009
8
Holt-oram syndrome and atrial fibrillation: opening the (T)-box. (18535267)
2008
9
A case of malignant pheochromocytoma with Holt-Oram syndrome. (18250543)
2008
10
Holt-Oram syndrome. (17502954)
2007
11
Molecular genetic and ocular findings in patients with holt-oram syndrome. (15823919)
2005
12
Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome. (15849237)
2005
13
Perinatal/neonatal case presentation: unexpected severe respiratory insufficiency in a newborn with Holt-Oram Syndrome. (16252013)
2005
14
Update: PGD and Holt-Oram syndrome. (15940699)
2005
15
TBX5, a gene mutated in Holt-Oram syndrome, is regulated through a GC box and T-box binding elements (TBEs). (15095414)
2004
16
Novel TBX5 mutations and molecular mechanism for Holt-Oram syndrome. (12624158)
2003
17
Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype. (12789647)
2003
18
A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. (11572777)
2001
19
Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. (11555635)
2001
20
Holt-Oram syndrome vs heart-hand syndrome. (10801768)
2000
21
Persistent left superior vena cava in Holt-Oram syndrome. (11221778)
2000
22
Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome. (10842287)
2000
23
Prenatal sonographic diagnosis of Holt-Oram syndrome. (10641008)
2000
24
Holt-Oram syndrome revisited. Two patients in the same family. (10887363)
1999
25
Variable clinical expression of Holt-Oram syndrome in three generations. (10028874)
1998
26
Mutations in human TBX5 cause limb and cardiac malformation in Holt- Oram syndrome. (8988165)
1997
27
The Holt-Oram syndrome: radiological approach. (9260393)
1997
28
A translocation at 12q2 refines the interval containing the Holt-Oram syndrome 1 gene. (8940280)
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
Holt-Oram syndrome in an elderly patient--a case history. (1632574)
1992
33
Holt-Oram syndrome. (1895500)
1991
34
Variability of the Holt-Oram syndrome in Saudi individuals. (3400729)
1988
35
Holt-Oram syndrome: delayed diagnosis. (3446267)
1987
36
Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. (3674114)
1987
37
Holt-Oram syndrome in a Puerto Rican family--case reports. (3425976)
1987
38
The Holt-Oram syndrome: a case presentation and review of management parameters. (3800624)
1987
39
Holt-Oram syndrome--a case report. (3467017)
1986
40
The antenatal ultrasonographic detection of the Holt-Oram syndrome. (3898414)
1985
41
Two patients with interstitial del (14q), one with features of Holt-Oram syndrome. Exclusion mapping of PI (alpha-1-antitrypsin). (6335371)
1984
42
Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. (7449488)
1981
43
The Holt Oram syndrome with previously undescribed associated anomalies. (7440473)
1980
44
The upper limb-cardiovascular syndrome (Holt-Oram syndrome). A survey and a report of four cases. (4761183)
1973
45
Congenital heart disease and upper extremity defects. A case report (Holt-Oram syndrome). (4266176)
1973
46
Holt Oram syndrome associated with carcinoma. (5559104)
1971
47
The Holt-Oram syndrome: the long and the short of it. (5413182)
1970
48
Atrial septal defect associated with skeletal anomalies (Holt-Oram syndrome). (5415973)
1970
49
Holt-Oram syndrome (Upper limb cardiovascular syndrome). (5917980)
1966
50
Holt-Oram syndrome: clinical and genetic study of a large family. (5904863)
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
29.4NKX2-5, KAT2B
39.2TBX1, TBX5, NKX2-5
49.2NKX2-5, TBX5, MYH6

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