Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and often causes heart problems.[1] The syndrome may include an absent radial bone in the forearm, an atrial septal defect in the heart, or heart block.[2] It affects approximately 1 in 100,000 people.[2]
All people with Holt-Oram syndrome have, at least one, abnormal wrist bone, which can often only be detected by X-ray.[1] Other bone abnormalities are associated with the syndrome. These vary widely in severity, and include a missing thumb, a thumb that looks like a finger, upper arm bones of unequal length or underdeveloped, partial or complete absence of bones in the forearm, and abnormalities in the collar bone or shoulder blade.[1][2] Bone abnormalities may affect only one side of the body or both sides; if both sides are affected differently, the left side is usually affected more severely.[1]
About 75 percent of individuals with Holt–Oram syndrome also have congenital heart problems,[2] with the most common being defects in the tissue wall between the upper chambers of the heart (atrial septal defect) or the lower chambers of the heart (ventricular septal defect).[3] People with Holt–Oram syndrome may also have abnormalities in the electrical system that coordinates contractions of the heart chambers.[1] Cardiac conduction disease can lead to slow heart rate (bradycardia); rapid, ineffective contraction of the heart muscles (fibrillation); and heart block.[1][2] People with Holt-Oram syndrome may have only congenital heart defects, only cardiac conduction disease, both or neither.[1][2]
GeneticsEdit
Mutations in the TBX5 gene cause Holt–Oram syndrome.[1] The TBX5 gene produces a protein that is critical for the proper development of the heart and upper limbs before birth.[1]
Holt–Oram syndrome has an autosomal dominant pattern of inheritance, meaning one abnormal copy of the gene is sufficient to cause disease, which each child has a 50% chance of inheriting from an affected parent.[1] However, in 85 percent of cases, the gene mutation isn't inherited, but a new mutation.[2]
DiagnosisEdit
Diagnosis may be made on physical features alone, if a person has an arm or hand bone abnormality and a personal or family history of heart problems.[2] If the symptoms aren't enough to diagnose, a person may undergo genetic testing for the mutations associated with the syndrome.[2]
TreatmentEdit
A person with Holt-Oram syndrome may need various treatments, depending on how the syndrome manifests. Surgery, prosthetics and physical or occupational therapy can help people with bone abnormalities.[2] Heart defects may call for surgery, medication, pacemakers or close monitoring.[2] Pregnant women with Holt-Oram syndrome and heart abnormalities should be followed by a cardiologist during pregnancy.[2]
HistoryEdit
It is named for Mary Holt and Samuel Oram, who published a paper on it in 1960.[4][5]
^ abcdefghij"Holt-Oram syndrome". Genetics Home Reference. U.S. National Library of Medicine. June 2014. Retrieved 18 April 2018.
^ abcdefghijklMcDermott, Deborah A.; Fong, Jamie C.; Basson, Craig T. (2015-10-08) [2004-07-20]. Adam, MP; Ardinger, HH; Pagon, RA; et al. (eds.). "Holt-Oram Syndrome". GeneReviews. Seattle, WA: University of Washington. PMID 20301290. Retrieved 2018-01-01 – via NCBI Bookshelf.
^Bossert, T; Walther, T; Gummert, J; Hubald, R; Kostelka, M; Mohr, FW (October 2002). "Cardiac malformations associated with the Holt-Oram syndrome—report on a family and review of the literature". The Thoracic and Cardiovascular Surgeon. 50 (5): 312–4. doi:10.1055/s-2002-34573. PMID 12375192.
^Virdis, G.; Dessole, M.; Dessole, S.; Ambrosini, G.; Cosmi, E.; Cherchil, P. L.; Capobianco, G. (2016-01-01). "Holt Oram syndrome: a case report and review of the literature". Clinical and Experimental Obstetrics & Gynecology. 43 (1): 137–139. doi:10.12891/ceog3060.2016. ISSN 0390-6663. PMID 27048037. S2CID 11803484.
^Holt, Mary; Oram, Samuel (1960-04-01). "Familial Heart Disease with Skeletal Malformations". British Heart Journal. 22 (2): 236–242. doi:10.1136/hrt.22.2.236. ISSN 0007-0769. PMC1017650. PMID 14402857.
Further readingEdit
GeneReview/NIH/UW entry on Holt-Oram Syndrome
External linksEdit
October 22, 2023
holt, oram, syndrome, also, called, atrio, digital, syndrome, atriodigital, dysplasia, cardiac, limb, syndrome, heart, hand, syndrome, type, ventriculo, radial, syndrome, autosomal, dominant, disorder, that, affects, bones, arms, hands, upper, limbs, often, ca. Holt Oram syndrome also called atrio digital syndrome atriodigital dysplasia cardiac limb syndrome heart hand syndrome type 1 HOS ventriculo radial syndrome is an autosomal dominant disorder that affects bones in the arms and hands the upper limbs and often causes heart problems 1 The syndrome may include an absent radial bone in the forearm an atrial septal defect in the heart or heart block 2 It affects approximately 1 in 100 000 people 2 Holt Oram syndromeOther namesHeart hand syndrome Atrio digital syndrome Atriodigital dysplasiaHolt Oram syndrome has an autosomal dominant pattern of inheritanceSpecialtyMedical genetics CausesMutations in the TBX5 gene Contents 1 Presentation 2 Genetics 3 Diagnosis 4 Treatment 5 History 6 See also 7 References 8 Further reading 9 External linksPresentation EditAll people with Holt Oram syndrome have at least one abnormal wrist bone which can often only be detected by X ray 1 Other bone abnormalities are associated with the syndrome These vary widely in severity and include a missing thumb a thumb that looks like a finger upper arm bones of unequal length or underdeveloped partial or complete absence of bones in the forearm and abnormalities in the collar bone or shoulder blade 1 2 Bone abnormalities may affect only one side of the body or both sides if both sides are affected differently the left side is usually affected more severely 1 About 75 percent of individuals with Holt Oram syndrome also have congenital heart problems 2 with the most common being defects in the tissue wall between the upper chambers of the heart atrial septal defect or the lower chambers of the heart ventricular septal defect 3 People with Holt Oram syndrome may also have abnormalities in the electrical system that coordinates contractions of the heart chambers 1 Cardiac conduction disease can lead to slow heart rate bradycardia rapid ineffective contraction of the heart muscles fibrillation and heart block 1 2 People with Holt Oram syndrome may have only congenital heart defects only cardiac conduction disease both or neither 1 2 Genetics EditMutations in the TBX5 gene cause Holt Oram syndrome 1 The TBX5 gene produces a protein that is critical for the proper development of the heart and upper limbs before birth 1 Holt Oram syndrome has an autosomal dominant pattern of inheritance meaning one abnormal copy of the gene is sufficient to cause disease which each child has a 50 chance of inheriting from an affected parent 1 However in 85 percent of cases the gene mutation isn t inherited but a new mutation 2 Diagnosis EditDiagnosis may be made on physical features alone if a person has an arm or hand bone abnormality and a personal or family history of heart problems 2 If the symptoms aren t enough to diagnose a person may undergo genetic testing for the mutations associated with the syndrome 2 Treatment EditA person with Holt Oram syndrome may need various treatments depending on how the syndrome manifests Surgery prosthetics and physical or occupational therapy can help people with bone abnormalities 2 Heart defects may call for surgery medication pacemakers or close monitoring 2 Pregnant women with Holt Oram syndrome and heart abnormalities should be followed by a cardiologist during pregnancy 2 History EditIt is named for Mary Holt and Samuel Oram who published a paper on it in 1960 4 5 See also EditAbsent radius Heart hand diseasesReferences Edit a b c d e f g h i j Holt Oram syndrome Genetics Home Reference U S National Library of Medicine June 2014 Retrieved 18 April 2018 a b c d e f g h i j k l McDermott Deborah A Fong Jamie C Basson Craig T 2015 10 08 2004 07 20 Adam MP Ardinger HH Pagon RA et al eds Holt Oram Syndrome GeneReviews Seattle WA University of Washington PMID 20301290 Retrieved 2018 01 01 via NCBI Bookshelf Bossert T Walther T Gummert J Hubald R Kostelka M Mohr FW October 2002 Cardiac malformations associated with the Holt Oram syndrome report on a family and review of the literature The Thoracic and Cardiovascular Surgeon 50 5 312 4 doi 10 1055 s 2002 34573 PMID 12375192 Virdis G Dessole M Dessole S Ambrosini G Cosmi E Cherchil P L Capobianco G 2016 01 01 Holt Oram syndrome a case report and review of the literature Clinical and Experimental Obstetrics amp Gynecology 43 1 137 139 doi 10 12891 ceog3060 2016 ISSN 0390 6663 PMID 27048037 S2CID 11803484 Holt Mary Oram Samuel 1960 04 01 Familial Heart Disease with Skeletal Malformations British Heart Journal 22 2 236 242 doi 10 1136 hrt 22 2 236 ISSN 0007 0769 PMC 1017650 PMID 14402857 Further reading EditGeneReview NIH UW entry on Holt Oram SyndromeExternal links Edit Retrieved from https en wikipedia org w index php title Holt Oram syndrome amp oldid 1144082740, wikipedia, wiki, book, books, library,
