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A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions.
Am J Med Genet A. 2018 03; 176(3):663-667.AJ

Abstract

Sheldon-Hall syndrome (SHS) is the most common of the distal arthrogryposes (DAs), a group of disorders characterized by congenital non-progressive contractures. Patients with SHS present with contractures of the limbs and a distinctive triangular facies with prominent nasolabial folds. Calcaneovalgus deformity is frequent, as well as camptodactyly and ulnar deviation. Causative mutations in at least four different genes have been reported (MYH3, TNNI2, TPM2, and TNNT3). MYH3 plays a pivotal role in fetal muscle development and mutations in this gene are associated with Freeman-Sheldon syndrome, distal arthrogryposis 8 (DA8), and autosomal dominant spondylocarpotarsal synostosis. The last two disorders are characterized by skeletal abnormalities, in particular bony fusions. The observation that MYH3 may be mutated in these syndromes has suggested the involvement of this gene in bone development. We report the case of a boy with a novel pathogenic MYH3 mutation, presenting with the classical clinical features of SHS in association with unilateral carpal bone fusion and multiple vertebral fusions. This distinctive phenotype has never been reported in the literature so far and expands the phenotypic spectrum of SHS, endorsing the clinical variability of patients with MYH3-related disorders. Our findings also support a role for MYH3 in both muscle and bone development, suggesting a phenotypic continuum in MYH3-related disorders.

Authors+Show Affiliations

UOC Neurochirurgia, Istituto Giannina Gaslini, Genoa, Italy.UOC Neurochirurgia, Istituto Giannina Gaslini, Genoa, Italy.UOC Neuropsichiatria, Istituto Giannina Gaslini, Genoa, Italy.UOC Clinica Pediatrica, Endocrinologia Clinica e Sperimentale, Istituto Giannina Gaslini, Università di Genova, Genoa, Italy.Prenatal Medicine Munich, Department of Molecular Genetics, Munich, Germany.Prenatal Medicine Munich, Department of Molecular Genetics, Munich, Germany.UOC Clinica Pediatrica, Endocrinologia Clinica e Sperimentale, Istituto Giannina Gaslini, Università di Genova, Genoa, Italy.UOC Neurochirurgia, Istituto Giannina Gaslini, Genoa, Italy.

Pub Type(s)

Case Reports
Journal Article
Review

Language

eng

PubMed ID

29314551

Citation

Scala, Marcello, et al. "A Novel Pathogenic MYH3 Mutation in a Child With Sheldon-Hall Syndrome and Vertebral Fusions." American Journal of Medical Genetics. Part A, vol. 176, no. 3, 2018, pp. 663-667.
Scala M, Accogli A, De Grandis E, et al. A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions. Am J Med Genet A. 2018;176(3):663-667.
Scala, M., Accogli, A., De Grandis, E., Allegri, A., Bagowski, C. P., Shoukier, M., Maghnie, M., & Capra, V. (2018). A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions. American Journal of Medical Genetics. Part A, 176(3), 663-667. https://doi.org/10.1002/ajmg.a.38593
Scala M, et al. A Novel Pathogenic MYH3 Mutation in a Child With Sheldon-Hall Syndrome and Vertebral Fusions. Am J Med Genet A. 2018;176(3):663-667. PubMed PMID: 29314551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions. AU - Scala,Marcello, AU - Accogli,Andrea, AU - De Grandis,Elisa, AU - Allegri,Anna, AU - Bagowski,Christoph P, AU - Shoukier,Moneef, AU - Maghnie,Mohamad, AU - Capra,Valeria, Y1 - 2018/01/05/ PY - 2017/09/12/received PY - 2017/11/27/revised PY - 2017/12/01/accepted PY - 2018/1/10/pubmed PY - 2019/3/1/medline PY - 2018/1/10/entrez KW - Sheldon-Hall syndrome KW - arthrogryposis KW - embryonic myosin heavy chain KW - vertebral fusions SP - 663 EP - 667 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 176 IS - 3 N2 - Sheldon-Hall syndrome (SHS) is the most common of the distal arthrogryposes (DAs), a group of disorders characterized by congenital non-progressive contractures. Patients with SHS present with contractures of the limbs and a distinctive triangular facies with prominent nasolabial folds. Calcaneovalgus deformity is frequent, as well as camptodactyly and ulnar deviation. Causative mutations in at least four different genes have been reported (MYH3, TNNI2, TPM2, and TNNT3). MYH3 plays a pivotal role in fetal muscle development and mutations in this gene are associated with Freeman-Sheldon syndrome, distal arthrogryposis 8 (DA8), and autosomal dominant spondylocarpotarsal synostosis. The last two disorders are characterized by skeletal abnormalities, in particular bony fusions. The observation that MYH3 may be mutated in these syndromes has suggested the involvement of this gene in bone development. We report the case of a boy with a novel pathogenic MYH3 mutation, presenting with the classical clinical features of SHS in association with unilateral carpal bone fusion and multiple vertebral fusions. This distinctive phenotype has never been reported in the literature so far and expands the phenotypic spectrum of SHS, endorsing the clinical variability of patients with MYH3-related disorders. Our findings also support a role for MYH3 in both muscle and bone development, suggesting a phenotypic continuum in MYH3-related disorders. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/29314551/A_novel_pathogenic_MYH3_mutation_in_a_child_with_Sheldon_Hall_syndrome_and_vertebral_fusions_ L2 - https://doi.org/10.1002/ajmg.a.38593 DB - PRIME DP - Unbound Medicine ER -