Format

Send to:

Choose Destination

Links from PubMed

Holt-Oram syndrome(HOS)

MedGen UID:
120524
Concept ID:
C0265264
Congenital Abnormality; Disease or Syndrome
Synonyms: Atrio digital syndrome; Atriodigital dysplasia; Cardiac-limb syndrome; Heart-hand syndrome; Heart-hand syndrome, type 1; HOS; HOS 1; TBX5-Related Holt-Oram Syndrome; Ventriculo-radial syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
892334
Concept ID:
CN000007
Functional Concept
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
SNOMED CT: Holt Oram syndrome (19092004); Holt-Oram syndrome (19092004); Cardiac-limb syndrome (19092004); Atrio-digital syndrome (19092004)
 
Gene (location): TBX5 (12q24.21)
OMIM®: 142900

Disease characteristics

Excerpted from the GeneReview: Holt-Oram Syndrome
Holt-Oram syndrome (HOS) is characterized by: Upper-extremity malformations involving radial, thenar, or carpal bones; and Variably, one or both of the following: Personal and/or family history of congenital heart malformation, most commonly ostium secundum atrial septal defect (ASD) and ventricular septal defect (VSD), especially those occurring in the muscular trabeculated septum. Cardiac conduction disease. An abnormal carpal bone is present in all affected individuals and may be the only evidence of disease. Seventy-five percent of individuals with HOS have a congenital heart malformation. [from GeneReviews]
Authors:
Deborah A McDermott  |  Jamie C Fong  |  Craig T Basson   view full author information

Additional descriptions

From OMIM
Holt-Oram syndrome is an autosomal dominant disorder characterized by abnormalities of the upper limbs and shoulder girdle, associated with a congenital heart lesion. The typical combination is considered to be a triphalangeal thumb with a secundum atrial septal defect (ASD), but there is a great range in the severity of both the heart and skeletal lesions (summary by Hurst et al., 1991).  http://www.omim.org/entry/142900
From GHR
Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals. Often, these wrist bone abnormalities can be detected only by x-ray. Individuals with Holt-Oram syndrome may have additional bone abnormalities including a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, the bone abnormalities can be the same or different on each side. In cases where the skeletal abnormalities are not the same on both sides of the body, the left side is usually more severely affected than the right side.About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. The most common problem is a defect in the muscular wall (septum) that separates the right and left sides of the heart. A hole in the septum between the upper chambers of the heart (atria) is called an atrial septal defect (ASD), and a hole in the septum between the lower chambers of the heart (ventricles) is called a ventricular septal defect (VSD). Some people with Holt-Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slower-than-normal heart rate (bradycardia) or a rapid and uncoordinated contraction of the heart muscle (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as ASD or VSD) or as the only heart problem in people with Holt-Oram syndrome.The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome; however, these two disorders are caused by mutations in different genes.  https://ghr.nlm.nih.gov/condition/holt-oram-syndrome

Clinical features

Conduction disorder of the heart
MedGen UID:
78114
Concept ID:
C0264886
Disease or Syndrome
Abnormality in rhythm of heartbeat, including rate, regularity, and/or sequence of activation abnormalities
Phocomelia
MedGen UID:
10721
Concept ID:
C0031575
Congenital Abnormality
Missing or malformed long bones of the extremities with the distal parts (such as hands and/or feet) connected to the variably shortened or even absent extremity, leading to a flipper-like appearance, as opposed to other forms of limb malformations were either the hole limb is missing (such as amelia), or the distal part of a limb is absent (peromelia).
Partial duplication of thumb phalanx
MedGen UID:
82716
Concept ID:
C0265608
Congenital Abnormality
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the thumb. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
A congenital deformity characterized by the presence of hypoplastic radius. It is usually associated with club hand deformity.
Abnormality of the carpal bones
MedGen UID:
374491
Concept ID:
C1840535
Finding
An abnormality affecting the carpal bones of the wrist (scaphoid, lunate, triquetral, pisiform, trapezium, trapezoid, capitate, hamate).
Aplasia/Hypoplasia of the radius
MedGen UID:
411844
Concept ID:
C2749463
Finding
A small/hypoplastic or absent/aplastic radius.
Aplasia/Hypoplasia of the thumb
MedGen UID:
465975
Concept ID:
C3179508
Finding
Hypoplastic/small or absent thumb.
Absent thumb
MedGen UID:
480441
Concept ID:
C3278811
Finding
Absent thumb, i.e., the absence of both phalanges of a thumb and the associated soft tissues.
Abnormality of the wrist
MedGen UID:
867379
Concept ID:
C4021744
Anatomical Abnormality
Abnormality of the wrist, the structure connecting the hand and the forearm.
Abnormality of the metacarpal bones
MedGen UID:
867414
Concept ID:
C4021785
Anatomical Abnormality
An abnormality of the metacarpal bones.
Aplasia of the pectoralis major muscle
MedGen UID:
869784
Concept ID:
C4024213
Anatomical Abnormality
Absence of the pectoralis major muscle.
Triphalangeal thumb
MedGen UID:
504759
Concept ID:
CN001116
Finding
A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.
Radioulnar synostosis
MedGen UID:
505426
Concept ID:
CN002691
Finding
An abnormal osseous union (fusion) between the radius and the ulna.
Abnormality of the humerus
MedGen UID:
428325
Concept ID:
CN002762
Finding
An abnormality of the humerus (i.e., upper arm bone).
Finger syndactyly
MedGen UID:
505885
Concept ID:
CN005347
Finding
Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are revered to as \
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Anatomical Abnormality
Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.
Pulmonary venous return anomaly
MedGen UID:
20675
Concept ID:
C0036400
Congenital Abnormality
Total anomalous pulmonary venous return (TAPVR) is a cyanotic form of congenital heart defect in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or one of the venous tributaries (summary by Bleyl et al., 1994).
Hypoplastic left heart syndrome
MedGen UID:
57746
Concept ID:
C0152101
Disease or Syndrome
Hypoplastic left heart syndrome results from defective development of the aorta proximal to the entrance of the ductus arteriosus and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged (Brekke, 1953). Genetic Heterogeneity of Hypoplastic Left Heart Syndrome Hypoplastic left heart syndrome-2 (HLHS2; 614435) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q35.1. Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with HLHS.
Conduction disorder of the heart
MedGen UID:
78114
Concept ID:
C0264886
Disease or Syndrome
Abnormality in rhythm of heartbeat, including rate, regularity, and/or sequence of activation abnormalities
Abnormality of the aorta
MedGen UID:
871269
Concept ID:
C4025756
Anatomical Abnormality
An abnormality of the aorta.
Patent ductus arteriosus
MedGen UID:
504886
Concept ID:
CN001496
Finding
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Pulmonary venous return anomaly
MedGen UID:
20675
Concept ID:
C0036400
Congenital Abnormality
Total anomalous pulmonary venous return (TAPVR) is a cyanotic form of congenital heart defect in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or one of the venous tributaries (summary by Bleyl et al., 1994).
Aplasia of the pectoralis major muscle
MedGen UID:
869784
Concept ID:
C4024213
Anatomical Abnormality
Absence of the pectoralis major muscle.
Phocomelia
MedGen UID:
10721
Concept ID:
C0031575
Congenital Abnormality
Missing or malformed long bones of the extremities with the distal parts (such as hands and/or feet) connected to the variably shortened or even absent extremity, leading to a flipper-like appearance, as opposed to other forms of limb malformations were either the hole limb is missing (such as amelia), or the distal part of a limb is absent (peromelia).
Partial duplication of thumb phalanx
MedGen UID:
82716
Concept ID:
C0265608
Congenital Abnormality
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the thumb. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
A congenital deformity characterized by the presence of hypoplastic radius. It is usually associated with club hand deformity.
Scoliosis
MedGen UID:
195976
Concept ID:
C0700208
Finding
The presence of an abnormal lateral curvature of the spine.
Abnormality of the carpal bones
MedGen UID:
374491
Concept ID:
C1840535
Finding
An abnormality affecting the carpal bones of the wrist (scaphoid, lunate, triquetral, pisiform, trapezium, trapezoid, capitate, hamate).
Abnormality of the ribs
MedGen UID:
330763
Concept ID:
C1842083
Anatomical Abnormality
An anomaly of the rib.
Thoracic scoliosis
MedGen UID:
387910
Concept ID:
C1857790
Finding
Abnormality of the sternum
MedGen UID:
349830
Concept ID:
C1860493
Finding
An anomaly of the sternum, also known as the breastbone.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest (\
Aplasia/Hypoplasia of the radius
MedGen UID:
411844
Concept ID:
C2749463
Finding
A small/hypoplastic or absent/aplastic radius.
Aplasia/Hypoplasia of the thumb
MedGen UID:
465975
Concept ID:
C3179508
Finding
Hypoplastic/small or absent thumb.
Absent thumb
MedGen UID:
480441
Concept ID:
C3278811
Finding
Absent thumb, i.e., the absence of both phalanges of a thumb and the associated soft tissues.
Abnormality of the wrist
MedGen UID:
867379
Concept ID:
C4021744
Anatomical Abnormality
Abnormality of the wrist, the structure connecting the hand and the forearm.
Abnormality of the metacarpal bones
MedGen UID:
867414
Concept ID:
C4021785
Anatomical Abnormality
An abnormality of the metacarpal bones.
Sprengel anomaly
MedGen UID:
504649
Concept ID:
CN000854
Finding
A congenital skeletal deformity characterized by the elevation of one scapula (thus, one scapula is located superior to the other).
Triphalangeal thumb
MedGen UID:
504759
Concept ID:
CN001116
Finding
A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.
Radioulnar synostosis
MedGen UID:
505426
Concept ID:
CN002691
Finding
An abnormal osseous union (fusion) between the radius and the ulna.
Abnormality of the shoulder
MedGen UID:
446468
Concept ID:
CN002749
Finding
An abnormality of the shoulder, which is defined as the structures surrounding the shoulder joint where the humerus attaches to the scapula.
Abnormality of the humerus
MedGen UID:
428325
Concept ID:
CN002762
Finding
An abnormality of the humerus (i.e., upper arm bone).
Finger syndactyly
MedGen UID:
505885
Concept ID:
CN005347
Finding
Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are revered to as \

Recent clinical studies

Etiology

Sunagawa S, Kikuchi A, Sano Y, Kita M, Ono K, Horikoshi T, Takagi K, Kawame H
Congenit Anom (Kyoto) 2009 Mar;49(1):38-41. doi: 10.1111/j.1741-4520.2008.00211.x. PMID: 19243417
Yoshihara A, Tanabe A, Saito H, Hizuka N, Ishizawa A, Horikawa R, Takano K
Endocr J 2008 Mar;55(1):153-9. Epub 2008 Feb 4 PMID: 18250543
Debeer P, Race V, Gewillig M, Devriendt K, Frijns JP
Clin Orthop Relat Res 2007 Sep;462:20-6. doi: 10.1097/BLO.0b013e3181123ffe. PMID: 17534187
Borozdin W, Bravo Ferrer Acosta AM, Bamshad MJ, Botzenhart EM, Froster UG, Lemke J, Schinzel A, Spranger S, McGaughran J, Wand D, Chrzanowska KH, Kohlhase J
Hum Mutat 2006 Sep;27(9):975-6. doi: 10.1002/humu.9449. PMID: 16917909
Kohlhase J, Schubert L, Liebers M, Rauch A, Becker K, Mohammed SN, Newbury-Ecob R, Reardon W
J Med Genet 2003 Jul;40(7):473-8. PMID: 12843316Free PMC Article

Diagnosis

Aung TT, Roberto ES, Wase A
Am J Case Rep 2016 Feb 17;17:93-6. PMID: 26882979Free PMC Article
Morine M, Kohmoto T, Masuda K, Inagaki H, Watanabe M, Naruto T, Kurahashi H, Maeda K, Imoto I
Am J Med Genet A 2015 Dec;167A(12):3192-6. Epub 2015 Sep 28 doi: 10.1002/ajmg.a.37359. PMID: 26780237
Wall LB, Piper SL, Habenicht R, Oishi SN, Ezaki M, Goldfarb CA
J Hand Surg Am 2015 Sep;40(9):1764-8. Epub 2015 Aug 1 doi: 10.1016/j.jhsa.2015.06.102. PMID: 26243320Free PMC Article
Jhang WK, Lee BH, Kim GH, Lee JO, Yoo HW
Cardiol Young 2015 Aug;25(6):1093-8. Epub 2014 Sep 12 doi: 10.1017/S1047951114001656. PMID: 25216260
Atik T, Dervisoglu H, Onay H, Ozkinay F, Cogulu O
J Trop Pediatr 2014 Jun;60(3):257-9. Epub 2014 Jan 9 doi: 10.1093/tropej/fmt109. PMID: 24408148

Therapy

Franklin AD, Lorinc AN, Donahue BS
J Cardiothorac Vasc Anesth 2014 Oct;28(5):1326-7. Epub 2013 Sep 5 doi: 10.1053/j.jvca.2013.03.017. PMID: 24011877
Tsai TC, Lu JK, Choo SL, Yeh SY, Tang RB, Lee HY, Lu JH
J Biomed Sci 2012 Jul 9;19:63. doi: 10.1186/1423-0127-19-63. PMID: 22776023Free PMC Article
Kohlhase J, Schubert L, Liebers M, Rauch A, Becker K, Mohammed SN, Newbury-Ecob R, Reardon W
J Med Genet 2003 Jul;40(7):473-8. PMID: 12843316Free PMC Article
el-Gindi E, Ahmed-Nasr M
Cardiovasc Surg 1993 Aug;1(4):381-3. PMID: 8076064
Van Regemorter N, Haumont D, Kirkpatrick C, Viseur P, Jeanty P, Dodion J, Milaire J, Rooze M, Rodesch F
Eur J Pediatr 1982 Feb;138(1):77-80. PMID: 7075631

Prognosis

Morine M, Kohmoto T, Masuda K, Inagaki H, Watanabe M, Naruto T, Kurahashi H, Maeda K, Imoto I
Am J Med Genet A 2015 Dec;167A(12):3192-6. Epub 2015 Sep 28 doi: 10.1002/ajmg.a.37359. PMID: 26780237
Yoshihara A, Tanabe A, Saito H, Hizuka N, Ishizawa A, Horikawa R, Takano K
Endocr J 2008 Mar;55(1):153-9. Epub 2008 Feb 4 PMID: 18250543
Le Meur N, Goldenberg A, Michel-Adde C, Drouin-Garraud V, Blaysat G, Marret S, Amara SA, Moirot H, Joly-Hélas G, Mace B, Kleinfinger P, Saugier-Veber P, Frébourg T, Rossi A
Am J Med Genet A 2005 May 1;134(4):439-42. doi: 10.1002/ajmg.a.30660. PMID: 15810003
He J, McDermott DA, Song Y, Gilbert F, Kligman I, Basson CT
Am J Med Genet A 2004 Apr 1;126A(1):93-8. doi: 10.1002/ajmg.a.20487. PMID: 15039979
Brassington AM, Sung SS, Toydemir RM, Le T, Roeder AD, Rutherford AE, Whitby FG, Jorde LB, Bamshad MJ
Am J Hum Genet 2003 Jul;73(1):74-85. Epub 2003 Jun 3 doi: 10.1086/376436. PMID: 12789647Free PMC Article

Clinical prediction guides

Morine M, Kohmoto T, Masuda K, Inagaki H, Watanabe M, Naruto T, Kurahashi H, Maeda K, Imoto I
Am J Med Genet A 2015 Dec;167A(12):3192-6. Epub 2015 Sep 28 doi: 10.1002/ajmg.a.37359. PMID: 26780237
Yoshihara A, Tanabe A, Saito H, Hizuka N, Ishizawa A, Horikawa R, Takano K
Endocr J 2008 Mar;55(1):153-9. Epub 2008 Feb 4 PMID: 18250543
Le Meur N, Goldenberg A, Michel-Adde C, Drouin-Garraud V, Blaysat G, Marret S, Amara SA, Moirot H, Joly-Hélas G, Mace B, Kleinfinger P, Saugier-Veber P, Frébourg T, Rossi A
Am J Med Genet A 2005 May 1;134(4):439-42. doi: 10.1002/ajmg.a.30660. PMID: 15810003
He J, McDermott DA, Song Y, Gilbert F, Kligman I, Basson CT
Am J Med Genet A 2004 Apr 1;126A(1):93-8. doi: 10.1002/ajmg.a.20487. PMID: 15039979
Brassington AM, Sung SS, Toydemir RM, Le T, Roeder AD, Rutherford AE, Whitby FG, Jorde LB, Bamshad MJ
Am J Hum Genet 2003 Jul;73(1):74-85. Epub 2003 Jun 3 doi: 10.1086/376436. PMID: 12789647Free PMC Article

Recent systematic reviews

Baban A, Postma AV, Marini M, Trocchio G, Santilli A, Pelegrini M, Sirleto P, Lerone M, Albanese SB, Barnett P, Boogerd CJ, Dallapiccola B, Digilio MC, Ravazzolo R, Pongiglione G
Am J Med Genet A 2014 Dec;164A(12):3100-7. Epub 2014 Sep 26 doi: 10.1002/ajmg.a.36783. PMID: 25263169
Stoll C, Dott B, Alembik Y, Roth MP
Genet Couns 2013;24(2):223-34. PMID: 24032294

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center