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

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A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. / Løseth, Sissel; Voermans, Nicol C; Torbergsen, Torberg; Lillis, Sue; Jonsrud, Christoffer; Lindal, Sigurd; Kamsteeg, Erik-Jan; Lammens, Martin; Broman, Marcus; Dekomien, Gabriele; Maddison, Paul; Muntoni, Francesco; Sewry, Caroline; Radunovic, Aleksandar; de Visser, Marianne; Straub, Volker; van Engelen, Baziel; Jungbluth, Heinz.

In: Journal of Neurology, Vol. 260, No. 6, 06.2013, p. 1504-10.

Research output: Contribution to journalArticle

Harvard

Løseth, S, Voermans, NC, Torbergsen, T, Lillis, S, Jonsrud, C, Lindal, S, Kamsteeg, E-J, Lammens, M, Broman, M, Dekomien, G, Maddison, P, Muntoni, F, Sewry, C, Radunovic, A, de Visser, M, Straub, V, van Engelen, B & Jungbluth, H 2013, 'A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene', Journal of Neurology, vol. 260, no. 6, pp. 1504-10. https://doi.org/10.1007/s00415-012-6817-7

APA

Løseth, S., Voermans, N. C., Torbergsen, T., Lillis, S., Jonsrud, C., Lindal, S., ... Jungbluth, H. (2013). A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Journal of Neurology, 260(6), 1504-10. https://doi.org/10.1007/s00415-012-6817-7

Vancouver

Løseth S, Voermans NC, Torbergsen T, Lillis S, Jonsrud C, Lindal S et al. A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Journal of Neurology. 2013 Jun;260(6):1504-10. https://doi.org/10.1007/s00415-012-6817-7

Author

Løseth, Sissel ; Voermans, Nicol C ; Torbergsen, Torberg ; Lillis, Sue ; Jonsrud, Christoffer ; Lindal, Sigurd ; Kamsteeg, Erik-Jan ; Lammens, Martin ; Broman, Marcus ; Dekomien, Gabriele ; Maddison, Paul ; Muntoni, Francesco ; Sewry, Caroline ; Radunovic, Aleksandar ; de Visser, Marianne ; Straub, Volker ; van Engelen, Baziel ; Jungbluth, Heinz. / A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. In: Journal of Neurology. 2013 ; Vol. 260, No. 6. pp. 1504-10.

Bibtex Download

@article{2bbd1e18cff948e9ab8677a22bafb972,
title = "A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene",
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).",
author = "Sissel L{\o}seth and Voermans, {Nicol C} and Torberg Torbergsen and Sue Lillis and Christoffer Jonsrud and Sigurd Lindal and Erik-Jan Kamsteeg and Martin Lammens and Marcus Broman and Gabriele Dekomien and Paul Maddison and Francesco Muntoni and Caroline Sewry and Aleksandar Radunovic and {de Visser}, Marianne and Volker Straub and {van Engelen}, Baziel and Heinz Jungbluth",
year = "2013",
month = "6",
doi = "10.1007/s00415-012-6817-7",
language = "English",
volume = "260",
pages = "1504--10",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "D. Steinkopff-Verlag",
number = "6",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene

AU - Løseth, Sissel

AU - Voermans, Nicol C

AU - Torbergsen, Torberg

AU - Lillis, Sue

AU - Jonsrud, Christoffer

AU - Lindal, Sigurd

AU - Kamsteeg, Erik-Jan

AU - Lammens, Martin

AU - Broman, Marcus

AU - Dekomien, Gabriele

AU - Maddison, Paul

AU - Muntoni, Francesco

AU - Sewry, Caroline

AU - Radunovic, Aleksandar

AU - de Visser, Marianne

AU - Straub, Volker

AU - van Engelen, Baziel

AU - Jungbluth, Heinz

PY - 2013/6

Y1 - 2013/6

N2 - 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).

AB - 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).

U2 - 10.1007/s00415-012-6817-7

DO - 10.1007/s00415-012-6817-7

M3 - Article

C2 - 23329375

VL - 260

SP - 1504

EP - 1510

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

IS - 6

ER -

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