Holt-Oram syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: HOS
HOS1
Atriodigital dysplasia
Heart-hand syndrome
Heart-hand syndrome type 1
Atriodigital dysplasia type 1
Number of Symptoms 45
OrphanetNr: 392
OMIM Id: 142900
ICD-10: Q87.2
UMLs: C0265264
MeSH: C535326
MedDRA: 10050469
Snomed: 19092004

Prevalence, inheritance and age of onset:

Prevalence: < 1 - PMID: 25344219 [IBIS]
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Genetic cardiac rhythm disease
 -Rare cardiac disease
 -Rare genetic disease
Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare genetic disease
Heart-hand syndrome
 -Rare bone disease
 -Rare developmental defect during embryogenesis
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare developmental defect during embryogenesis
Rare syndrome with cardiac malformations
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0030680) Abnormality of cardiovascular system morphology 25216260 IBIS 355 / 7739
2
(HPO:0006101) Finger syndactyly Occasional [Orphanet] 26243320 IBIS 198 / 7739
3
(HPO:0002650) Scoliosis Occasional [Orphanet] 17502954 IBIS 705 / 7739
4
(HPO:0003468) Abnormality of the vertebrae 25344219 IBIS 77 / 7739
5
(HPO:0000912) Sprengel anomaly Occasional [Orphanet] 1870097 IBIS 51 / 7739
6
(HPO:0000766) Abnormality of the sternum 7.5000 % [HPO] 25468972 IBIS 31 / 7739
7
(HPO:0003063) Abnormality of the humerus Occasional [Orphanet] 25344219 IBIS 36 / 7739
8
(HPO:0009829) Phocomelia Occasional [Orphanet] 10.9756 % [HPO] 25344219 IBIS 20 / 7739
9
(HPO:0002984) Hypoplasia of the radius 37.8049 % [HPO] 25344219 IBIS 44 / 7739
10
(HPO:0001227) Abnormality of the thenar eminence 18351627 IBIS 1 / 7739
11
(HPO:0002818) Abnormality of the radius Frequent [Orphanet] 26243320 IBIS 96 / 7739
12
(HPO:0001191) Abnormality of the carpal bones 24826304 IBIS 6 / 7739
13
(HPO:0003019) Abnormality of the wrist Very frequent [Orphanet] 24826304 IBIS 52 / 7739
14
(HPO:0002943) Thoracic scoliosis 7.5000 % [HPO] 6519847 IBIS 12 / 7739
15
(HPO:0009944) Partial duplication of thumb phalanx 26243320 IBIS 7 / 7739
16
(HPO:0002973) Abnormality of the forearm 14402857 IBIS 3 / 7739
17
(HPO:0000774) Narrow chest Occasional [Orphanet] 22190901 IBIS 167 / 7739
18
(HPO:0002817) Abnormality of the upper limb 26243320 IBIS 25 / 7739
19
(HPO:0009777) Absent thumb 1870097 IBIS 31 / 7739
20
(HPO:0009751) Aplasia of the pectoralis major muscle 7.5000 % [HPO] 8730285 IBIS 8 / 7739
21
(HPO:0001163) Abnormality of the metacarpal bones Frequent [Orphanet] 25344219 IBIS 149 / 7739
22
(HPO:0001172) Abnormality of the thumb Occasional [Orphanet] 26243320 IBIS 103 / 7739
23
(HPO:0009601) Aplasia/Hypoplasia of the thumb Frequent [Orphanet] 26243320 IBIS 80 / 7739
24
(HPO:0002974) Radioulnar synostosis Occasional [Orphanet] 21637475 IBIS 52 / 7739
25
(HPO:0000767) Pectus excavatum Occasional [Orphanet] 24879328 IBIS 244 / 7739
26
(HPO:0000772) Abnormality of the ribs Occasional [Orphanet] 21637475 IBIS 146 / 7739
27
(HPO:0001643) Patent ductus arteriosus Occasional [Orphanet] 7.5000 % [HPO] 24879328 IBIS 228 / 7739
28
(HPO:0012303) Abnormality of the aortic arch Occasional [Orphanet] 18685167 IBIS 57 / 7739
29
(HPO:0001631) Atria septal defect Frequent [Orphanet] 41.4634 % [HPO] 25344219 IBIS 274 / 7739
30
(HPO:0001629) Ventricular septal defect Frequent [Orphanet] 14.6341 % [HPO] 25344219 IBIS 316 / 7739
31
(HPO:0011025) Abnormality of cardiovascular system physiology Frequent [Orphanet] 25344219 IBIS 41 / 7739
32
(HPO:0001671) Abnormality of the cardiac septa 25344219 IBIS 55 / 7739
33
(HPO:0006695) Atrioventricular canal defect Occasional [Orphanet] 24664498 IBIS 27 / 7739
34
(HPO:0001678) Atrioventricular block 25216260 IBIS 59 / 7739
35
(HPO:0004383) Hypoplastic left heart Occasional [Orphanet] 2766565 IBIS 29 / 7739
36
(HPO:0011675) Arrhythmia 25216260 IBIS 226 / 7739
37
(HPO:0010772) Anomalous pulmonary venous return Occasional [Orphanet] 24879328 IBIS 11 / 7739
38
(HPO:0001688) Sinus bradycardia 15292570 IBIS 18 / 7739
39
(HPO:0001961) Hypoplastic heart 2766565 IBIS 9 / 7739
40
(OMIM) Asymmetric involvement 8730285 IBIS 1 / 7739
41
(HPO:0001199) Triphalangeal thumb Frequent [Orphanet] 26243320 IBIS 56 / 7739
42
(OMIM) Limited forearm pronation and supination 14402857 IBIS 3 / 7739
43
(MedDRA:10000032) Cardiac conduction disorders 25216260 IBIS 5 / 7739
44
(OMIM) Congenital heart malformation 25216260 IBIS 3 / 7739
45
(OMIM) Radial-ulnar anomalies 12789647 IBIS 1 / 7739

Associated genes:

TBX5;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
TBX5 rs104894377 pathogenic RCV000008456.3
TBX5 rs104894379 pathogenic RCV000008463.2
TBX5 rs104894381 pathogenic RCV000008458.2
TBX5 rs104894382 pathogenic RCV000008459.2
TBX5 rs104894383 pathogenic RCV000008461.2
TBX5 rs104894384 pathogenic RCV000008462.2

Additional Information:

Molecular genetics OMIM Li et al. (1997) and Basson et al. (1997) demonstrated mutations in the TBX5 (601620) gene as the basis of this disorder. The dominant phenotype of HOS appears to result from haploinsufficiency of TBX5. The glu69-to-ter mutation (601620.0002) identified ...
Diagnosis GeneReviews The diagnosis of Holt-Oram syndrome (HOS) can be established clinically. The diagnostic criteria have been validated with molecular testing [McDermott et al 2005]. Clinical findings in HOS:...
Clinical Description GeneReviews Holt-Oram syndrome is characterized by upper-limb defects, congenital heart malformation, and cardiac conduction disease [Holt & Oram 1960]....
Genotype-Phenotype Correlations GeneReviews It has been reported that missense mutations at the 5' end of the T-box (which binds the major groove of the target DNA sequence) are associated with more serious cardiac defects. ...
Differential Diagnosis GeneReviews The following diagnoses can be considered when anomalies involving the ulna, lower limbs, kidneys, genitourinary system, vertebrae, craniofaces, and auditory or ocular systems are present [Newbury-Ecob et al 1996, Allanson & Newbury-Ecob 2003, Bressan et al 2003]: ...
Management GeneReviews To establish the extent of disease and needs in an individual diagnosed with Holt-Oram syndrome, the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....