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Erschienen in: Journal of Neurology 6/2013

01.06.2013 | Original Communication

A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene

verfasst von: Sissel Løseth, Nicol C. Voermans, Torberg Torbergsen, Sue Lillis, Christoffer Jonsrud, Sigurd Lindal, Erik-Jan Kamsteeg, Martin Lammens, Marcus Broman, Gabriele Dekomien, Paul Maddison, Francesco Muntoni, Caroline Sewry, Aleksandar Radunovic, Marianne de Visser, Volker Straub, Baziel van Engelen, Heinz Jungbluth

Erschienen in: Journal of Neurology | Ausgabe 6/2013

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Abstract

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are a common cause of inherited neuromuscular disorders and have been associated with a wide clinical spectrum, ranging from various congenital myopathies to the malignant hyperthermia susceptibility (MHS) trait without any associated weakness. RYR1-related myopathies are usually of early-childhood onset. Here we present 11 patients from 8 families with a late-onset axial myopathy associated with RYR1 variants. Patients presented between the third and seventh decade of life to neuromuscular centres in Norway, the Netherlands and the United Kingdom with predominant axial muscle involvement, comprising variable degrees of lumbar hyperlordosis, scapular winging and/or camptocormia. Marked myalgia was commonly associated. Serum creatine kinase levels were normal or moderately elevated. Muscle imaging showed consistent involvement of the lower paravertebral muscles and the posterior thigh. Muscle biopsy findings were often discrete, featuring variability in fibre size, increased internal nuclei and unevenness of oxidative enzyme staining, but only rarely overt cores. RYR1 sequencing revealed heterozygous missense variants, either previously associated with the MHS trait or localizing to known MHS mutational hotspots. These findings indicate that MHS-related RYR1 mutations may present later in life with prominent axial weakness but not always typical histopathological features. We propose a combined effect of RyR1 dysfunction, aging and particular vulnerability of axial muscle groups as a possible pathogenic mechanism. RYR1 is a candidate for cases with “idiopathic” camptocormia or bent spine syndrome (BSS).
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Metadaten
Titel
A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene
verfasst von
Sissel Løseth
Nicol C. Voermans
Torberg Torbergsen
Sue Lillis
Christoffer Jonsrud
Sigurd Lindal
Erik-Jan Kamsteeg
Martin Lammens
Marcus Broman
Gabriele Dekomien
Paul Maddison
Francesco Muntoni
Caroline Sewry
Aleksandar Radunovic
Marianne de Visser
Volker Straub
Baziel van Engelen
Heinz Jungbluth
Publikationsdatum
01.06.2013
Verlag
Springer-Verlag
Erschienen in
Journal of Neurology / Ausgabe 6/2013
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-012-6817-7

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