PATOLOGIAS CONCRETAS. ARTICULOS RECIENTES RELACIONADOS

MIOPATIAS CONGENITAS
http://www.ncbi.nlm.nih.gov/pubmed/18769251?dopt=AbstractPlus

1: Curr Opin Neurol. 2008 Oct;21(5):569-75. Links
Congenital myopathies.
Sewry CA, Jimenez-Mallebrera C, Muntoni F.
Dubowitz Neuromuscular Centre, Nationally Commissioned Centre for Congenital Muscular Dystrophies and Congenital Myopathies Institute of Child Health and Great Ormond Street Hospital for Children, London, UK. c.sewry@imperial.ac.uk

PURPOSE OF REVIEW: The present review aims to discuss the pathological and clinical heterogeneity of congenital myopathies, and the overlap between the different variants highlighted by recent studies. RECENT FINDINGS: The spectrum of pathological changes associated with known gene defects has widened, and new genes responsible for rare structural defects have been identified. The complexity of the classification of these conditions is highlighted by the realization that defects in the same gene can result in diverse phenotypes, including disorders traditionally classified as congenital myopathies with structural abnormalities, adult-onset disorders, conditions characterized by distal weakness and wasting, or distal arthrogryposis. There is a wider appreciation of the complexities of inheritance and of the value of noninvasive assessment, such as muscle MRI. New animal models provide a better understanding of pathogenesis and are highlighting therapeutic possibilities. SUMMARY: The overlap of clinical and pathological features in the congenital myopathies has led to the recognition that diverse disorders are often associated with the same causative gene, and is challenging traditional classifications. Identification of further causative genes and development of new models will further the understanding of pathogenesis and development of therapies.

Related Articles Review Distal myopathies. [Semin Neurol. 1999] ReviewCongenital myopathies and related disorders. [Curr Opin Neurol. 2002] ReviewCongenital myopathies. [Curr Opin Neurol. 2007] The heterogeneity of distal arthrogryposis. [Brain Dev. 1984] ReviewCongenital myopathies: diseases of the actin cytoskeleton. [J Pathol. 2004] » See Reviews... | » See All...


SINDROME DE FREEMAN-SHELDON

-ETIOLOGÍA:

Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally.Tajsharghi H, Kimber E, Kroksmark AK, Jerre R, Tulinius M, Oldfors A.
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden. homa.tajsharghi@gu.se

BACKGROUND: Myosin is a molecular motor and the essential part of the thick filament of striated muscle. The expression of myosin heavy-chain (MyHC) isoforms is developmentally regulated. The embryonic isoform encoded from MYH3 (OMIM *160720) is expressed during fetal life. Recently, mutations in MYH3 were demonstrated to be associated with congenital joint contractures, that is, Freeman-Sheldon and Sheldon-Hall syndromes, which are both distal arthrogryposis syndromes. Mutations in other MyHC isoforms cause myopathy. It is unknown whether MYH3 mutations cause myopathy because muscle tissue has not been studied. OBJECTIVES: To determine whether novel MYH3 mutations are associated with distal arthrogryposis and to demonstrate myopathic changes in muscle biopsy specimens from 4 patients with distal arthrogryposis and MYH3 mutations. DESIGN: In a cohort of patients with distal arthrogryposis, we analyzed the entire coding sequence of MYH3. Muscle biopsy specimens were obtained, and in addition to morphologic analysis, the expression of MyHC isoforms was investigated at the protein and transcript levels. RESULTS: We identified patients from 3 families with novel MYH3 mutations. These mutations affect developmentally conserved residues that are located in different regions of the adenosine triphosphate-binding pocket of the MyHC head. The embryonic (MYH3) isoform was not detected in any of the muscle biopsy samples, indicating a normal developmental downregulation of MYH3 in these patients. However, morphologic analysis of muscle biopsy specimens from the 4 patients revealed mild and variable myopathic features and a pathologic upregulation of the fetal MyHC isoform (MYH8) in 1 patient. CONCLUSIONS: Distal arthrogryposis associated with MYH3 mutations is secondary to myosin myopathy, and postnatal muscle manifestations are variable.

PMID: 18695058 [PubMed - in process]

Related ArticlesHereditary myosin myopathies. [Neuromuscul Disord. 2007] Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. [Nat Genet. 2006] Myopathies associated with myosin heavy chain mutations. [Acta Myol. 2004] A mutation in the fast skeletal muscle troponin I gene causes myopathy and distal arthrogryposis. [Neurology. 2006] Induced shift in myosin heavy chain expression in myosin myopathy by endurance training. [J Neurol. 2004] » See all Related Articles...

SINDROME DE SHELDON HALL

1: Orphanet J Rare Dis. 2009 Mar 23;4(1):11.
Sheldon-Hall syndrome.Toydemir RM, Bamshad MJ.
ABSTRACT: Sheldon-Hall syndrome (SHS) is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate. Epidemiological data for the prevalence of SHS are not available, but less than 100 cases have been reported in the literature. Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. Typically, the contractures are most severe at birth and non-progressive. SHS is inherited in an autosomal dominant pattern but about half the cases are sporadic. Mutations in either MYH3, TNNI2, or TNNT3 have been found in about 50% of cases. These genes encode proteins of the contractile apparatus of fast twitch skeletal muscle fibers. The diagnosis of SHS is based on clinical criteria. Mutation analysis is useful to distinguish SHS from arthrogryposis syndromes with similar features (e.g. distal arthrogryposis 1 and Freeman-Sheldon syndrome). Prenatal diagnosis by ultrasonography is feasible at 18-24 weeks of gestation. If the family history is positive and the mutation is known in the family, prenatal molecular genetic diagnosis is possible. There is no specific therapy for SHS. However, patients benefit from early intervention with occupational and physical therapy, serial casting, and/or surgery. Life expectancy and cognitive abilities are normal.

PMID: 19309503 [PubMed - as supplied by publisher]

Related Articles:
-Clinical analysis of a variant of Freeman-Sheldon syndrome (DA2B). [Am J Med Genet. 1998]
-Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. [Nat Genet. 2006]
-Skeletal Muscle Contractile Gene (TNNT3, MYH3, TPM2) Mutations Not Found in Vertical Talus or Clubfoot.[Clin Orthop Relat Res. 2009]
-The distal arthrogryposes: delineation of new entities--review and nosologic discussion. [Am J Med Genet. 1982]
-Freeman-Sheldon syndrome. A case report and review of the literature. [Chir Organi Mov. 2008] »