HOS
MCID: HLT001
MIFTS: 62

Holt-Oram Syndrome (HOS) malady

Genetic diseases, Rare diseases, Cardiovascular diseases, Bone diseases, Fetal diseases categories

Summaries for Holt-Oram Syndrome

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44NIH Rare Diseases, 48OMIM, 20GeneReviews, 34MalaCards
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NIH Rare Diseases:44 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 HOS, is related to ventricular septal defect and congenital heart disease, 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 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 prostate, and related mouse phenotypes are limbs/digits/tail and skeleton.

Description from OMIM:48 142900

GeneReviews summary for hos

Aliases & Classifications for Holt-Oram Syndrome

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20GeneReviews, 44NIH Rare Diseases, 23GTR, 22Genetics Home Reference, 48OMIM, 46Novoseek, 50Orphanet, 63UMLS, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

50
holt-oram syndrome:
Inheritance: Autosomal dominant; Age of onset: Neonatal/infancy; Age of death: Any age


Aliases & Descriptions:

holt-oram syndrome 20 44 23 22 48 46 50 63
hos 44 22 50
heart-hand syndrome, type 1 44 22
ventriculo-radial syndrome 44 22
atriodigital dysplasia 44 22
cardiac-limb syndrome 44 22
atriodigital dysplasia type 1 50
heart-hand syndrome type 1 50
atrio-digital syndrome 22
atrio digital syndrome 44
heart-hand syndrome 44
holt oram syndrome 46
hearthand syndrome 20
hos 1 44


External Ids:

OMIM48 142900
MESH via Orphanet37 C535326
ICD10 via Orphanet27 Q87.2
SNOMED-CT via Orphanet60 19092004
UMLS via Orphanet64 C0265264

Related Diseases for Holt-Oram Syndrome

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

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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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

142900

Clinical features from OMIM:

142900

Symptoms:

50 (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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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-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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23GTR
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Genetic tests related to Holt-Oram Syndrome:

id Genetic test Affiliating Genes
1 Holt-Oram Syndrome23

Anatomical Context for Holt-Oram Syndrome

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34MalaCards
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MalaCards organs/tissues related to Holt-Oram Syndrome:

34
Heart, Bone, Prostate, Testes, Lung

Animal Models for Holt-Oram Syndrome or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Holt-Oram Syndrome:

38
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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53PubMed
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Articles related to Holt-Oram Syndrome:

(show top 50)    (show all 167)
idTitleAuthorsYear
1
A New Mutation in the TBX5 Gene in Holt-Oram Syndrome: Two Cases in the Same Family and Prenatal Diagnosis. (24408148)
2014
2
Unexplained right atrial enlargement may be a sign of Holt-Oram syndrome in the fetus. (24185902)
2013
3
Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. (24011877)
2013
4
Anesthetic implications in Holt-Oram Syndrome. (23545878)
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
Prenatal sonographic diagnosis of familial Holt-Oram syndrome associated with type B interrupted aortic arch. (18685167)
2008
12
Picture of the month. Holt-Oram syndrome. (17606836)
2007
13
Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. (17366586)
2007
14
Holt-oram syndrome with hemizygous continuation of inferior vena cava. (16551828)
2006
15
Molecular genetic and ocular findings in patients with holt-oram syndrome. (15823919)
2005
16
Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome. (15849237)
2005
17
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
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
A gene for Holt-Oram syndrome maps to the distal long arm of chromosome 12. (8054983)
1994
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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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Holt-Oram Syndrome:

65
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:

1
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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2BioGPS, 16Gene Expression Omnibus DataSets
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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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51PathCards, 56Reactome, 39NCBI BioSystems Database, 31KEGG
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Compounds for genes affiliated with Holt-Oram Syndrome

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46Novoseek, 25HMDB
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Compounds related to Holt-Oram Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1zinc46 259.0NKX2-5, SRSF2, SALL4, KAT2B

GO Terms for genes affiliated with Holt-Oram Syndrome

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17Gene Ontology
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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:0435658.8TBX1, TBX3, TBX5, NKX2-5
2transcription factor bindingGO:0081348.7TBX5, NKX2-5, KAT2B
3DNA bindingGO:0036778.6TBX1, TBX5, NKX2-5, SALL4
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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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet