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Genotype-phenotype relationships in Freeman-Sheldon syndrome.
Am J Med Genet A. 2014 Nov; 164A(11):2808-13.AJ

Abstract

Distal arthrogryposis (DA) syndromes are a group of disorders characterized by multiple congenital contractures. DA type 2A (DA2A or Freeman-Sheldon syndrome), caused by mutations in MYH3, is typically considered the most severe of the DA syndromes. However, there is wide phenotypic variability among individuals with DA2A. We characterized genotype-phenotype relationships in 46 families with DA2A. MYH3 mutations were found in 43/46 (93%) kindreds, with three mutations (p.T178I, p.R672C, and p.R672H) explaining 39/43 (91%) of cases. Phenotypic severity varied significantly by genotype (P=0.0055). Individuals with p.T178I were the most severely affected with both facial contractures and congenital scoliosis. Classification of individuals with DA2A into phenotypic groups of varying severity should facilitate providing families with more accurate information about natural history and suggests that individuals might benefit from personalized medical management motivated by MYH3 genotype.

Authors+Show Affiliations

Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington; Seattle Children's Hospital, Seattle, Washington.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25256237

Citation

Beck, Anita E., et al. "Genotype-phenotype Relationships in Freeman-Sheldon Syndrome." American Journal of Medical Genetics. Part A, vol. 164A, no. 11, 2014, pp. 2808-13.
Beck AE, McMillin MJ, Gildersleeve HI, et al. Genotype-phenotype relationships in Freeman-Sheldon syndrome. Am J Med Genet A. 2014;164A(11):2808-13.
Beck, A. E., McMillin, M. J., Gildersleeve, H. I., Shively, K. M., Tang, A., & Bamshad, M. J. (2014). Genotype-phenotype relationships in Freeman-Sheldon syndrome. American Journal of Medical Genetics. Part A, 164A(11), 2808-13. https://doi.org/10.1002/ajmg.a.36762
Beck AE, et al. Genotype-phenotype Relationships in Freeman-Sheldon Syndrome. Am J Med Genet A. 2014;164A(11):2808-13. PubMed PMID: 25256237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-phenotype relationships in Freeman-Sheldon syndrome. AU - Beck,Anita E, AU - McMillin,Margaret J, AU - Gildersleeve,Heidi I S, AU - Shively,Kathryn M B, AU - Tang,Andy, AU - Bamshad,Michael J, Y1 - 2014/09/25/ PY - 2014/05/01/received PY - 2014/08/08/accepted PY - 2014/9/27/entrez PY - 2014/9/27/pubmed PY - 2016/5/18/medline KW - arthrogryposis KW - clubfoot KW - congenital foot deformities KW - congenital hand deformities KW - congenital limb deformities KW - congenital lower extremity deformities KW - congenital upper extremity deformities KW - contracture KW - distal arthrogryposis KW - distal arthrogryposis type 2A KW - human MYH3 polypeptide KW - muscle KW - musculoskeletal abnormalities KW - myosin heavy chains KW - skeletal muscle SP - 2808 EP - 13 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 164A IS - 11 N2 - Distal arthrogryposis (DA) syndromes are a group of disorders characterized by multiple congenital contractures. DA type 2A (DA2A or Freeman-Sheldon syndrome), caused by mutations in MYH3, is typically considered the most severe of the DA syndromes. However, there is wide phenotypic variability among individuals with DA2A. We characterized genotype-phenotype relationships in 46 families with DA2A. MYH3 mutations were found in 43/46 (93%) kindreds, with three mutations (p.T178I, p.R672C, and p.R672H) explaining 39/43 (91%) of cases. Phenotypic severity varied significantly by genotype (P=0.0055). Individuals with p.T178I were the most severely affected with both facial contractures and congenital scoliosis. Classification of individuals with DA2A into phenotypic groups of varying severity should facilitate providing families with more accurate information about natural history and suggests that individuals might benefit from personalized medical management motivated by MYH3 genotype. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/25256237/Genotype_phenotype_relationships_in_Freeman_Sheldon_syndrome_ L2 - https://doi.org/10.1002/ajmg.a.36762 DB - PRIME DP - Unbound Medicine ER -