Journal of Neurology

, Volume 260, Issue 6, pp 1504–1510 | Cite as

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

  • 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 JungbluthEmail author
Original Communication


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).


Skeletal muscle ryanodine receptor (RYR1) gene RYR1 mutations Malignant hyperthermia susceptibility (MHS) Axial myopathy Camptocormia 



The authors wish to thank all participating families. Family members gave consent to the publication of their photographs and information. Support from the National Commissioning Group (NCG) of the United Kingdom to the Dubowitz Neuromuscular Centre and Guy’s Hospital is gratefully acknowledged. We would like to thank Dr Mark Davis, Perth, Western Australia, for constructive discussions and critically reading our manuscript.

Conflicts of interest

The authors do have no conflict of interest to declare.

Supplementary material

415_2012_6817_MOESM1_ESM.doc (59 kb)
Supplementary material 1 (DOC 59 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sissel Løseth
    • 1
    • 2
  • Nicol C. Voermans
    • 3
  • Torberg Torbergsen
    • 1
  • Sue Lillis
    • 4
  • Christoffer Jonsrud
    • 5
  • Sigurd Lindal
    • 6
    • 7
  • Erik-Jan Kamsteeg
    • 8
  • Martin Lammens
    • 9
  • Marcus Broman
    • 10
  • Gabriele Dekomien
    • 11
  • Paul Maddison
    • 12
  • Francesco Muntoni
    • 13
  • Caroline Sewry
    • 13
  • Aleksandar Radunovic
    • 14
  • Marianne de Visser
    • 15
  • Volker Straub
    • 16
  • Baziel van Engelen
    • 3
  • Heinz Jungbluth
    • 17
    • 18
    • 19
    Email author
  1. 1.Department of Neurology and NeurophysiologyUniversity Hospital of North NorwayTromsøNorway
  2. 2.Department of Clinical MedicineUniversity of TromsøTromsøNorway
  3. 3.Department of NeurologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  4. 4.Diagnostic DNA Laboratory, GSTS PathologyLondonUK
  5. 5.Department of Medical GeneticsUniversity Hospital of North NorwayTromsøNorway
  6. 6.Department of PathologyUniversity Hospital of North NorwayTromsøNorway
  7. 7.Department of Medical BiologyUniversity of TromsøTromsøNorway
  8. 8.Department of Human GeneticsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  9. 9.Department of PathologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  10. 10.Department of Anaesthesiology and Intensive CareSkåne University Hospital LundMalmøSweden
  11. 11.Department of Human GeneticsRuhr UniversityBochumGermany
  12. 12.Department of NeurologyNottingham University HospitalsNottinghamUK
  13. 13.Dubowitz Neuromuscular Centre, ICHLondonUK
  14. 14.Department of NeurologyRoyal London HospitalLondonUK
  15. 15.Department of NeurologyAcademic Medical CentreAmsterdamThe Netherlands
  16. 16.Institute of Genetic Medicine, International Centre for LifeUniversity of Newcastle upon TyneNewcastle upon TyneUK
  17. 17.Clinical Neuroscience Division, IOPKing’s CollegeLondonUK
  18. 18.Department of Paediatric Neurology, Neuromuscular, ServiceEvelina Children’s Hospital, St Thomas’ HospitalLondonUK
  19. 19.Children’s Neurosciences CentreSt Thomas’ HospitalLondonUK

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