Holt–Oram syndrome

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Holt-Oram syndrome
Autosomal dominant - en.svg
Holt-Oram syndrome has an autosomal dominant pattern of inheritance
Specialty Medical genetics Edit this on Wikidata

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]

Presentation[edit]

All people with Holt-Oram syndrome have an abnormality in a wrist bone (carpal bones), which can often only be detected X-ray.[1] Bone abnormalities associated with the syndrome otherwise vary widely in severity, and include a missing thumb, a thumb that looks like a finger (Triphalangeal thumb), upper arm bones of unequal length, partial or complete absence of bones in the forearm, an underdeveloped upper arm bone (Humerus), and abnormalities in the collar bone (clavicle) or shoulder blade (scapula).[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 cardiac conduction disease, or 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[edit]

Mutations in the TBX5 gene cause Holt–Oram syndrome.[1] The TBX5 gene is critical for a protein that affects development of the heart and upper limbs before birth.[1]

Holt–Oram syndrome has an autosomal dominant pattern of inheritance, meaning a child can inherit the affected gene from just one affected parent.[1] However, in 85 percent of cases, the gene mutation isn't inherited, but a new (de novo) mutation.[2]

Diagnosis[edit]

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]

Treatment[edit]

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]

History[edit]

It is named for Mary Holt and Samuel Oram, who published a paper on it in 1960.[4][5]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ a b c d e f g h i j k l McDermott DA, Fong JC, Basson CT. Holt-Oram Syndrome. 2004 Jul 20 [Updated 2015 Oct 8]. In Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1111/
  3. ^ 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. Retrieved 7 November 2012. 
  4. ^ 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. ISSN 0390-6663. PMID 27048037. 
  5. ^ 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 1017650Freely accessible. PMID 14402857. 

Further reading[edit]

External links[edit]

Classification
External resources