RYR1-related myopathies: a wide spectrum of phenotypes throughout life

被引：105

作者：

Snoeck, M. ^{[1
]}

van Engelen, B. G. M. ^{[2
]}

Kusters, B. ^{[3
,4
]}

Lammens, M. ^{[3
,5
]}

Meijer, R. ^{[6
]}

Molenaar, J. P. F. ^{[2
]}

Raaphorst, J. ^{[2
,7
]}

Verschuuren-Bemelmans, C. C. ^{[8
]}

Straathof, C. S. M. ^{[9
]}

Sie, L. T. L. ^{[10
]}

de Coo, I. F. ^{[11
]}

van der Pol, W. L. ^{[12
]}

de Visser, M. ^{[7
]}

Scheffer, H. ^{[6
]}

Treves, S. ^{[13
,14
]}

Jungbluth, H. ^{[15
,16
,17
]}

Voermans, N. C. ^{[2
]}

Kamsteeg, E. -J. ^{[6
]}

机构：

[1] Canisius Wilhelmina Hosp, Dept Anesthesiol, Natl MH Invest Unit, Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 HB Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands

[4] Maastricht Univ, Med Ctr, Dept Pathol, NL-6200 MD Maastricht, Netherlands

[5] Univ Antwerp, Univ Antwerp Hosp, Dept Pathol, Edegem, Belgium

[6] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[7] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands

[8] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[9] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands

[10] Haga Hosp, Juliana Childrens Hospital, Dept Neuropediat, Nijmegen, Netherlands

[11] Erasmus MC, Dept Neurol, Rotterdam, Netherlands

[12] Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands

[13] Univ Basel Hosp, Dept Anesthesia, CH-4031 Basel, Switzerland

[14] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland

[15] Guys & St Thomas Hosp NHS Fdn Trust, Evelina Childrens Hosp, Dept Paediat Neurol, Neuromuscular Serv, London, England

[16] Kings Coll London, Muscle Signalling Sect, Randall Div Cell & Mol Biophys, London, England

[17] Kings Coll London, IoPPN, Dept Basic & Clin Neurosci, London, England

来源：

EUROPEAN JOURNAL OF NEUROLOGY | 2015年 / 22卷 / 07期

关键词：

anaesthesia; congenital myopathy; core myopathy; malignant hyperthermia susceptibility; ryanodine receptor; RYR1; RECESSIVE RYR1 MUTATIONS; CENTRAL CORE DISEASE; RYANODINE RECEPTOR RYR1; MALIGNANT HYPERTHERMIA; CONGENITAL MYOPATHY; COMMON-CAUSE; GENE; IDENTIFICATION; DOMINANT; DEPLETION;

D O I：

10.1111/ene.12713

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and purposeAlthough several recent studies have implicated RYR1 mutations as a common cause of various myopathies and the malignant hyperthermia susceptibility (MHS) trait, many of these studies have been limited to certain age groups, confined geographical regions or specific conditions. The aim of the present study was to investigate the full spectrum of RYR1-related disorders throughout life and to use this knowledge to increase vigilance concerning malignant hyperthermia. MethodsA retrospective cohort study was performed on the clinical, genetic and histopathological features of all paediatric and adult patients in whom an RYR1 mutation was detected in a national referral centre for both malignant hyperthermia and inherited myopathies (2008-2012). ResultsThe cohort of 77 non-related patients (detection rate 28%) included both congenital myopathies with permanent weakness and induced' myopathies such as MHS and non-anaesthesia-related episodes of rhabdomyolysis or hyperCKemia, manifested throughout life and triggered by various stimuli. Sixty-one different mutations were detected, of which 24 were novel. Some mutations are present in both dominant (MHS) and recessive modes (congenital myopathy) of inheritance, even within families. Histopathological features included an equally wide spectrum, ranging from only subtle abnormalities to prominent cores. ConclusionsThis broad range of RYR1-related disorders often presents to the general paediatric and adult neurologist. Its recognition is essential for genetic counselling and improving patients' safety during anaesthesia. Future research should focus on invitro testing by the invitro contracture test and functional characterization of the large number of RYR1 variants whose precise effects currently remain uncertain.

引用

页码：1094 / 1112

页数：19

共 48 条

[1] Genotype-phenotype correlations in recessive RYR1-related myopathies [J].

Amburgey, Kimberly ;

Bailey, Angela ;

Hwang, Jean H. ;

Tarnopolsky, Mark A. ;

Bonnemann, Carsten G. ;

Medne, Livija ;

Mathews, Katherine D. ;

Collins, James ;

Daube, Jasper R. ;

Wellman, Gregory P. ;

Callaghan, Brian ;

Clarke, Nigel F. ;

Dowling, James J. .

ORPHANET JOURNAL OF RARE DISEASES, 2013, 8

[2]

Barone V, 1999, J MED GENET, V36, P115

[3] Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization [J].

Bevilacqua, J. A. ;

Monnier, N. ;

Bitoun, M. ;

Eymard, B. ;

Ferreiro, A. ;

Monges, S. ;

Lubieniecki, F. ;

Taratuto, A. L. ;

Laquerriere, A. ;

Claeys, K. G. ;

Marty, I. ;

Fardeau, M. ;

Guicheney, P. ;

Lunardi, J. ;

Romero, N. B. .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2011, 37 (03) :271-284

[4] Severe congenital RYR1-associated myopathy The expanding clinicopathologic and genetic spectrum [J].

Bharucha-Goebel, Diana Xerxes ;

Santi, Mariarita ;

Medne, Livija ;

Zukosky, Kristin ;

Dastgir, Jahannaz ;

Shieh, Perry B. ;

Winder, Thomas ;

Tennekoon, Gihan ;

Finkel, Richard S. ;

Dowling, James J. ;

Monnier, Nicole ;

Boennemann, Carsten G. .

NEUROLOGY, 2013, 80 (17) :1584-1589

[5] An Integrated Diagnosis Strategy for Congenital Myopathies [J].

Bohm, Johann ;

Vasli, Nasim ;

Malfatti, Edoardo ;

Le Gras, Stephanie ;

Feger, Claire ;

Jost, Bernard ;

Monnier, Nicole ;

Brocard, Julie ;

Karasoy, Hatice ;

Gerard, Marion ;

Walter, Maggie C. ;

Reilich, Peter ;

Biancalana, Valerie ;

Kretz, Christine ;

Messaddeq, Nadia ;

Marty, Isabelle ;

Lunardi, Joel ;

Romero, Norma B. ;

Laporte, Jocelyn .

PLOS ONE, 2013, 8 (06)

[6] Ryanodine Receptor Type I Gene Variants in the Malignant Hyperthermia-Susceptible Population of the United States [J].

Brandom, Barbara W. ;

Bina, Saiid ;

Wong, Cynthia A. ;

Wallace, Tarina ;

Visoiu, Mihaela ;

Isackson, Paul J. ;

Vladutiu, Georgirene D. ;

Sambuughin, Nyamkhishig ;

Muldoon, Sheila M. .

ANESTHESIA AND ANALGESIA, 2013, 116 (05) :1078-1086

[7] Mutation screening of the RYR1-cDNA from peripheral B-lymphocytes in 15 Swedish malignant hyperthermia index cases [J].

Broman, M. ;

Gehrig, A. ;

Islander, G. ;

Bodelsson, M. ;

Ranklev-Twetman, E. ;

Ruffert, H. ;

Muller, C. R. .

BRITISH JOURNAL OF ANAESTHESIA, 2009, 102 (05) :642-649

[8] A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree [J].

Brown, RL ;

Pollock, AN ;

Couchman, KG ;

Hodges, M ;

Hutchinson, DO ;

Waaka, R ;

Lynch, P ;

McCarthy, TV ;

Stowell, KM .

HUMAN MOLECULAR GENETICS, 2000, 9 (10) :1515-1524

[9] A RYR1 MUTATION ASSOCIATED WITH RECESSIVE CONGENITAL MYOPATHY AND DOMINANT MALIGNANT HYPERTHERMIA IN ASIAN FAMILIES [J].

Carpenter, Danielle ;

Ismail, Azzam ;

Robinson, Rachel L. ;

Ringrose, Christopher ;

Booms, Patrick ;

Iles, David E. ;

Halsall, P. Jane ;

Steele, Derek ;

Shaw, Marie-Anne ;

Hopkins, Philip M. .

MUSCLE & NERVE, 2009, 40 (04) :633-639

[10] Exercise-Induced Rhabdomyolysis and Stress-Induced Malignant Hyperthermia Events, Association with Malignant Hyperthermia Susceptibility, and RYR1 Gene Sequence Variations [J].

Carsana, Antonella .

SCIENTIFIC WORLD JOURNAL, 2013,

← 1 2 3 4 5 →