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Sheldon-Hall syndrome

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Description

Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term "arthrogryposis" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). "Distal" refers to areas of the body away from the center. The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity called ulnar deviation in which all of the fingers are angled outward toward the fifth (pinky) finger. Inward- and upward-turning feet (a condition called clubfoot) is also commonly seen in Sheldon-Hall syndrome. The specific hand and foot abnormalities vary among affected individuals; the abnormalities are present at birth and generally do not get worse over time.

People with Sheldon-Hall syndrome also usually have distinctive facial features, which include a triangular face; outside corners of the eyes that point downward (down-slanting palpebral fissures); deep folds in the skin between the nose and lips (nasolabial folds); and a small mouth with a high, arched roof of the mouth (palate). Other features that may occur in Sheldon-Hall syndrome include extra folds of skin on the neck (webbed neck) and short stature.

Sheldon-Hall syndrome does not usually affect other parts of the body, and intelligence and life expectancy are normal in this disorder.

Frequency

The prevalence of Sheldon-Hall syndrome is unknown; however, it is thought to be the most common type of distal arthrogryposis. About 100 affected individuals have been described in the medical literature.

Causes

Sheldon-Hall syndrome can be caused by mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene. These genes provide instructions for making proteins that are involved in muscle tensing (contraction).

Muscle contraction occurs when thick filaments made of proteins called myosins slide past thin filaments made of proteins called actins. The MYH3 gene provides instructions for making a myosin protein that is normally active only before birth and is important for early development of the muscles.

The process of muscle contraction is controlled (regulated) by other proteins called troponins and tropomyosins, which affect the interaction of myosin and actin. Certain troponin proteins are produced from the TNNI2 and TNNT3 genes. The TPM2 gene provides instructions for making a tropomyosin protein.

Mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene likely interfere with normal muscle development or prevent muscle contractions from being properly controlled, resulting in the contractures and other muscle and skeletal abnormalities associated with Sheldon-Hall syndrome. It is unknown why the contractures mainly affect the hands and feet or how these gene mutations are related to other features of this disorder.

Inheritance

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 50 percent of cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Other Names for This Condition

  • arthrogryposis multiplex congenita, distal, type 2B
  • DA2B
  • distal arthrogryposis type 2B
  • SHS

Additional Information & Resources

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am. 2009 Jul;91 Suppl 4:40-6. doi: 10.2106/JBJS.I.00281. Review. Citation on PubMed or Free article on PubMed Central
  • Beck AE, McMillin MJ, Gildersleeve HI, Kezele PR, Shively KM, Carey JC, Regnier M, Bamshad MJ. Spectrum of mutations that cause distal arthrogryposis types 1 and 2B. Am J Med Genet A. 2013 Mar;161A(3):550-5. doi: 10.1002/ajmg.a.35809. Epub 2013 Feb 7. Citation on PubMed or Free article on PubMed Central
  • Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M. Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet. 2003 Mar;72(3):681-90. Citation on PubMed or Free article on PubMed Central
  • Toydemir RM, Bamshad MJ. Sheldon-Hall syndrome. Orphanet J Rare Dis. 2009 Mar 23;4:11. doi: 10.1186/1750-1172-4-11. Review. Citation on PubMed or Free article on PubMed Central
  • Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet. 2006 May;38(5):561-5. Epub 2006 Apr 16. Citation on PubMed
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