MALIGNANT hyperthermia (MH) is an inherited disorder of skeletal muscle that manifests clinically as a hypermetabolic crisis when a susceptible individual receives a halogenated inhalational anesthetic agent or succinylcholine.1–3  The clinical signs that ensue from this exposure in susceptible individuals include hypercapnia, masseter muscle and/or generalized muscle rigidity, acidosis, peaked T waves that indicate hyperkalemia, and hyperthermia and are caused by the dysregulated entry of myoplasmic calcium, which results in a hypermetabolic cascade involving sustained muscular contractures, depletion of adenosine triphosphate, and muscle cell death.4  The inheritance of pathogenic variants (i.e., mutations) in three genes are primarily associated with MH susceptibility and account for the genetic basis of approximately 70% of patients investigated (fig. 1). The majority of MH–associated variants are found within the RYR1 gene that encodes the skeletal muscle ryanodine receptor type I protein.2,5–7  This protein regulates the movement of calcium from the sarcoplasmic reticulum into the intracellular space of the muscle cell. In MH–susceptible individuals, abnormalities of the ryanodine receptor result in the accumulation of excessive myoplasmic calcium in the presence of one of the anesthetic triggering agents. Nearly 700 variants have been identified in RYR1; however, only 35 have been functionally validated as MH–causative pathogenic variants (an up-to-date list as well as the criteria for causality may be found at the European Malignant Hyperthermia Group website).8  The remainder await validation studies.

Fig. 1.

Depiction of the skeletal muscle cell excitation–contraction complex and the different pathologic variants that may result in malignant hyperthermia susceptibility. ADP = adenosine diphosphate; ATP = adenosine triphosphate; CCD = central core disease; CFTD = congenital fiber type disproportion; CNM = centronuclear myopathy; DHP = dihydropyridine; KDS = King–Denborough syndrome; SERCA = sarcoplasmic/endoplasmic reticulum Ca2+-adenosine triphosphatase.

Fig. 1.

Depiction of the skeletal muscle cell excitation–contraction complex and the different pathologic variants that may result in malignant hyperthermia susceptibility. ADP = adenosine diphosphate; ATP = adenosine triphosphate; CCD = central core disease; CFTD = congenital fiber type disproportion; CNM = centronuclear myopathy; DHP = dihydropyridine; KDS = King–Denborough syndrome; SERCA = sarcoplasmic/endoplasmic reticulum Ca2+-adenosine triphosphatase.

The most common RYR1 variants that confer susceptibility to MH result from gain-of-function mutations in specific amino acids and regions of the RYR1 protein. These mutations may arise de novo or may be inherited, and the MH phenotype manifests variable expressivity and incomplete penetrance. Inheritance of MH causative pathogenic variants is suspected in individuals with a history of a likely MH clinical event or in those patients with a family history of MH susceptibility or a likely MH event. The mainstay of prevention of MH is the identification of these genetically susceptible individuals so that clinicians can then avoid triggering anesthetic agents.

There is a wide range of both dominant and recessive disorders associated with RYR1 pathogenic variants, and many of these inherited myopathies and related conditions have been linked with MH susceptibility.9–11  Therefore, in clinical anesthesia practice, MH susceptibility has often been assumed in patients with nonspecific muscle weakness but without a definitive diagnosis. This shotgun approach is less than ideal because most causes of muscle weakness are not associated with MH susceptibility, and this process then only results in the inaccurate labeling of patients (and their families) who would otherwise be able to safely receive volatile anesthetic agents and succinylcholine.

In this article, we build upon and summarize a body of data that have linked specific genotypic or phenotypic findings with susceptibility to MH and offer suggestions to anesthesiologists about the types of patients that should or should not receive a trigger-free general anesthetic. We discuss anesthetic management of certain congenital myopathies that may predispose to MH–like symptoms during general anesthesia, and we offer an approach to the anesthetic management of the undiagnosed patient with muscle weakness.

Diseases Associated with MH Susceptibility

The most common diseases associated with MH susceptibility are those associated with known RYR1-associated phenotypes, the “ryanodinopathies” (table 1). Not all patients with one of these clinical phenotypes or a proven RYR1 myopathy will assuredly be susceptible to MH, but because MH susceptibility and myopathy co-occur in a relatively large percentage of individuals with an RYR1 pathogenic variant (estimated to be at least 30% of individuals with RYR1 myopathies),12  they should be considered MH–susceptible unless proven negative by a specialized MH contracture biopsy.*17,18  In addition, it must be stressed that the clinical spectrum of the ryanodinopathies is broad, often changes with the age of the patient, and is potentially variable even within the same family where the causative pathogenic variants are the same.10 

Table 1.

Phenotypes Associated with MH Susceptibility

Phenotypes Associated with MH Susceptibility
Phenotypes Associated with MH Susceptibility

Patients with an RYR1 pathogenic variant, whether or not they exhibit MH susceptibility, may appear clinically normal and may not demonstrate typical phenotypic findings of a neuromuscular disease. In fact, most patients who have demonstrated clinical MH and who have an RYR1 variant have no overt clinical phenotype.19–21  Some may even demonstrate enhanced muscle mass and above average athletic skills.22  A subset of these phenotypically normal patients may develop rhabdomyolysis in response to certain conditions such as heat, exercise, administration of statin medications, or viral illness.23–32  It is estimated that MH–related RYR1 pathogenic variants may account for between 20 and 30% of cases of heat- or exercise-induced rhabdomyolysis.4  Some of these patients may demonstrate an elevated baseline serum creatine kinase level,6  and some may exhibit bleeding tendencies.33  Patients without a phenotypic or genotypic diagnosis that have demonstrated exaggerated or frequent muscle breakdown under normal or atypical conditions should be assumed to have an underlying RYR1 pathogenic variant that confers MH susceptibility, should not receive anesthetic triggering agents, and should undergo diagnostic neuromuscular and genetic evaluation.34–38 

Some patients with an RYR1 variant demonstrate a clinically evident myopathy of varying degrees in the absence of administration of anesthetic triggering agents.39,40  In fact, RYR1 variants are the most common cause of nondystrophic muscle disease in children.4  Histopathologic phenotypes that have been associated with RYR1 variants include central core disease,40,41  multiminicore myopathy,40,42–45  congenital myopathy with cores and rods,46,47  centronuclear myopathy,48  and congenital fiber type disproportion.49  Importantly, however, patients with RYR1 variants may have histopathologic findings that change with age and also may only have nonspecific myopathic or dystrophic changes. Patients with an RYR1 variant may manifest King–Denborough syndrome, an extremely rare but classically described condition that is characterized by dysmorphic features, abnormal gait, and MH susceptibility.50–53 

For the various histopathologic subtypes of congenital myopathy, only those individuals with an RYR1 variant (as well as CACNA1S and STAC3, see below) are linked to MH susceptibility. However, many of these patients have been phenotyped (i.e., histologic findings on muscle biopsy plus clinical characteristics) without confirmatory genetic analysis and thus are also considered MH–susceptible before genetic testing studies. Conversely, patients with these phenotypes and a confirmed causative variant other than RYR1 are not considered MH–susceptible. As an example, a patient with nemaline myopathy associated with a confirmed RYR1 variant is considered MH–susceptible,54  whereas a patient with the same disease caused by a variant of NEB or ACTA1 (among others) would not be considered MH–susceptible and does not need MH precautions.

It is well known that patients with acute or progressive muscle atrophy (i.e., congenital myopathy patients and many individuals with other forms of muscle disease) may demonstrate exaggerated release of myoplasmic potassium after administration of succinylcholine.55,56  Although these patients should not receive succinylcholine, it is not for the purpose of avoiding MH. This is discussed more fully below.

Less common loci of causality of MH susceptibility (approximately 2% of cases) are variants in the α-1 subunit of the dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor (CACNA1S), also part of the excitation–contraction complex in skeletal muscle. MH causative variants in CACNA1S have been associated with a normal clinical phenotype,57–59  as well as with congenital myopathies that resemble some subtypes of RYR1 myopathy60,61  and dynamic phenotypes like potassium-related periodic paralysis.62,63  Patients with periodic paralysis without genetic confirmation and those with a documented MH–causative RYR1 or CACNA1S variant should be considered MH–susceptible. It is not yet clear whether patients with recessive CACNA1S-related myopathies will be at risk of MH and for now should be considered MH–susceptible until further data are available.61  Periodic paralysis is also associated with variants in SCN4A, which is not associated with MH susceptibility.64,65 

Last, MH susceptibility is associated with pathologic variants in the STAC3 gene. These variants are manifested most commonly as Native American myopathy,66–68  a rare disorder found in the Lumbee Native Americans of North Carolina. More recently, individuals with MH outside of the Lumbee population have also been reported to have STAC3 variants, but the exact association between STAC3, MH susceptibility, and the other features of Native American Myopathy are not yet clear.

In the modern era of increasingly accessible genetic analysis, we can now more precisely associate certain diseases with MH susceptibility based on the presence of similar variants that alter the contractile apparatus and its response to exposure to anesthetic triggering agents. However, there is no definitive method by which to characterize with certainty the link between an inherited condition and MH susceptibility. Therefore, patients with a personal or family history of an MH–like event related to the administration of general anesthesia and who have demonstrated the presence of an RYR1, CACNA1S, or STAC3 gene variant should be considered MH–susceptible unless proven negative by contracture biopsy. Patients with associated phenotypes that have not been characterized by genotype should also be considered MH–susceptible until found to have an unrelated variant that is not associated with MH susceptibility.

Diseases Associated with Non-MH Anesthetic-induced Rhabdomyolysis

Some myopathic conditions have been associated with the development of fatal or life-threatening rhabdomyolysis upon exposure to volatile anesthetic agents or succinylcholine (table 2). The most common of these conditions are Duchenne and Becker muscular dystrophy. Although rhabdomyolysis with hyperkalemia can be a feature of MH, the MH syndrome usually manifests signs of hypermetabolism, such as respiratory acidosis, metabolic acidosis, and excessive heat production. The development of life-threatening rhabdomyolysis with hyperkalemia after administration of succinylcholine to patients with Duchenne or Becker muscular dystrophy is well documented;69  therefore, succinylcholine is contraindicated in patients with these disorders and other conditions with acute or progressive muscle atrophy (e.g., acute burns, stroke, and others).55  The use of volatile anesthetics without succinylcholine have been reported to cause non–MH–related rhabdomyolysis and hyperkalemia in patients with these dystrophies,70–75  and even though published case series have documented the safe administration of volatile agents to patients with Duchenne and Becker dystrophy,76,77  some authors and patient organizations have advocated the strict avoidance of volatile anesthetics in this patient population.78–81  Conversely, the use of intravenous anesthesia alone has been implicated in the development of heart failure related to preexisting disease in patients with Duchenne dystrophy.82,83  Thus, existing and potential comorbidities (i.e., cardiac and respiratory dysfunction) in this patient population may also be important factors that determine overall perioperative outcomes.84  Other myopathies reported to be associated with rhabdomyolysis around the time of administration of general anesthesia include carnitine palmitoyltransferase type 2 deficiency85,86  and merosin-deficient congenital muscular dystrophy.87,88  There is currently insufficient evidence to make firm suggestions for avoidance of MH–triggering anesthetics in patients with these phenotypic entities.

Table 2.

Diseases Associated with Non-MH Anesthetic-induced Rhabdomyolysis

Diseases Associated with Non-MH Anesthetic-induced Rhabdomyolysis
Diseases Associated with Non-MH Anesthetic-induced Rhabdomyolysis

There exist a number of case reports that describe distinct phenotypic entities that have, on occasion, demonstrated MH or an MH–like syndrome (i.e., hyperthermia, rhabdomyolysis, and others) in response to volatile anesthetic agents. Invariably, these reports do not contain enough information to confirm a clinical diagnosis of MH, and there is not an established genetic link between the phenotype and an MH–associated genotype. For these reasons, we do not consider them to have a known or suggested association with MH susceptibility. They include Schwartz–Jampel syndrome, Noonan syndrome, arthrogryposis multiplex congenita, all mitochondrial myopathies, osteogenesis imperfecta, and Freeman–Sheldon syndrome.89–94 

Approach to Undiagnosed Hypotonic Patients

One of the most vexing clinical situations faced by anesthesiologists is how to determine the MH–susceptibility status of a hypotonic and/or weak patient that has not yet received a phenotypic or genotypic diagnosis. Although the clinical spectrum of the ryanodinopathies is extensive,95  it would be unreasonably cautious to consider all hypotonic patients (and their extended families) to be MH–susceptible because most hypotonia in children is central in origin.96  Because RYR1 variants presently constitute the most common nondystrophic type of congenital muscle disease, we suggest that genetic testing be performed before muscle biopsy because current recommendations for the evaluation of congenital myopathies and congenital muscular dystrophies are now favoring genetic testing before biopsy in the diagnostic process.97  However, in the absence of a diagnosis, patients should be considered MH–susceptible when they possess any of the following clinical characteristics: (1) statement from the patient’s primary physician or other healthcare worker that they or a closely related family member are suspected to have an RYR1-, CACNA1S-, or STAC3-related myopathy based on their medical history or physical findings; (2) personal or closely related family history of suspected MH during general anesthesia with triggering agents in the absence of a negative contracture biopsy (i.e., caffeine–halothane contracture test or in vitro contracture test); or (3) personal or closely related family history of frequent exaggerated episodes of creatine kinase increase, rigidity, or evidence of rhabdomyolysis in response to exercise, heat exposure, or statin administration.

Ideally, infants with hypotonia should have a neurologic consultation before the administration of general anesthesia to provide the anesthesia team with the best possible information about their diagnosis and risk of MH susceptibility. In neonates with hypotonia, nearly all underlying diagnoses are not associated with an increased risk of MH. Most cases of neonatal hypotonia are caused by central nervous system dysfunction such as hypoxic ischemic encephalopathy or chromosomal syndromes such as trisomy 21, and these conditions are distinguishable from myopathies by history and examination. In the setting of weakness in an older child where a muscle disease may be suspected, nontriggering agents may be considered until the appropriate diagnosis has been established or when RYR1, CACNA1S, and STAC3 mutations have been excluded. However, the extensive clinical experience of the authors has shown that these conservative measures are unnecessary because of the paucity of cases of intraoperative MH in these undiagnosed children when triggering anesthetics are used.

Anesthesiologists should be well versed about the anesthetic implications of the diagnoses and should consult with an MH expert from the Malignant Hyperthermia Association of the United States to determine the risk of MH with triggering agents. The decision about the most appropriate anesthetic technique should be discussed beforehand with the surgical team as well as with the patient, and/or their parents when applicable, especially when the diagnosis is unknown.

Who Needs a Nontriggering Technique?

In this review, we attempted to develop a categorization scheme that uses phenotypic and genotypic classifications to determine the types of diseases that are linked with MH susceptibility (table 3). Nearly all of the diseases associated with MH susceptibility can reasonably be assumed to be due to pathogenic variants in RYR1, with a few additional patients having variants of CACNA1S and STAC3 that are also associated with MH susceptibility. Although the preponderance of patients with MH susceptibility may appear phenotypically normal, MH is associated with certain defined clinical phenotypes related to RYR1 variants including but not limited to central core disease, multiminicore myopathy, congenital myopathy with cores and rods, congenital fiber type disproportion, centronuclear myopathy, and, rarely, King–Denborough syndrome. An increased incidence of MH susceptibility has also been noted in patients that have experienced exaggerated and repeated (and sometimes fatal38 ) rhabdomyolysis as a result of heat, exercise, or statin administration. A unique situation that may occasionally be encountered is a patient with a proven RYR1 variant that has not been strictly characterized as causative according to the European Malignant Hyperthermia Group criteria. The MH susceptibility status of these patients should be made on a case-by-case basis, taking into account other pertinent factors in the history and physical examination, such as evidence of previous MH in the patient or their family and input from experts in the genetic testing for MH.14 

Table 3.

Who Needs a Nontriggering Technique?

Who Needs a Nontriggering Technique?
Who Needs a Nontriggering Technique?

Until further knowledge in this area has accumulated, there will be areas of uncertainty where anesthesiologists will have to use their contextual clinical judgment regarding whether to proceed with a nontriggering technique without definitive cause, thus labeling the patient and their family as MH–susceptible for an indefinite period. For example, in Brody myopathy with fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ adenosine triphosphatase mutations,98  there is only slight evidence of a possible link between the disease and MH susceptibility,99  but the pathophysiologic aspects of the disease would suggest that anesthetic triggering agents may cause an abnormal increase in myoplasmic calcium, triggering an MH–like event. In cases like this, avoidance of triggering agents is probably the safest approach, even though a definitive link is unproven. A more common example where anesthesiologists must use their contextual judgment is when a healthy patient presents with a vague history of a relative who developed hyperthermia in the perioperative period, often in the distant past, and no medical records about that relative’s episode are available. This situation should prompt a thorough, yet time-sensitive review of the medical history of the family in an attempt to search for comorbidities, other complications or MH–like episodes during anesthesia, and occurrences of previous anesthetics with and without triggering agents. Administration of both triggering and nontriggering agents may be reasonably justifiable, depending on the individual circumstances.

Other degenerative primary muscle disorders, such as Duchenne or Becker muscular dystrophy, are associated with development of life-threatening rhabdomyolysis during or immediately after exposure to triggering agents, but this response does not represent classic MH because of the lack of concomitant hypermetabolic symptoms. These patients should not receive succinylcholine or inhaled anesthetic agents unless indicated for unavoidable clinical reasons.

Acknowledments

The authors gratefully acknowledge the assistance of the anonymous reviewers, who greatly enhanced the quality of this paper, and Henry Rosenberg, M.D., director of medical education and clinical research, Saint Barnabas Medical Center, Livingston, New Jersey, for his lifelong dedication to helping patients with MH, and for his unselfish collegiality that made possible the academic careers of many MH researchers and educators, and resulted in the publication of this paper.

Research Support

Support was provided solely from institutional and/or departmental sources.

Competing Interests

The authors declare no competing interests.

*

MH contracture testing is considered the “gold standard” for diagnosis of an individual’s MH susceptibility and is the only way to rule out MH susceptibility. In North America, it is referred to as the caffeine–halothane contracture test (CHCT), and in Europe, it is referred to as the in vitro contracture test (IVCT). Although there are minor differences in methodology, both contracture tests are based on the contractile response of the individual’s fresh muscle tissue when it is bathed in caffeine and halothane. The sensitivity (true negative) of the CHCT is 97% (95% CI, 84 to 100%),13  and the sensitivity of the IVCT conducted according to the European Malignant Hyperthermia Group protocol has been reevaluated as 100%.14  Therefore, patients who have tested negative by CHCT or IVCT are ruled out for MH susceptibility and may safely receive triggering agents.15,16 

References

References
1.
Denborough
M
:
Malignant hyperthermia.
Lancet
1998
;
352
:
1131
6
2.
Rosenberg
H
,
Pollock
N
,
Schiemann
A
,
Bulger
T
,
Stowell
K
:
Malignant hyperthermia: A review.
Orphanet J Rare Dis
2015
;
10
:
93
3.
Hopkins
PM
:
Malignant hyperthermia: Advances in clinical management and diagnosis.
Br J Anaesth
2000
;
85
:
118
28
4.
Jungbluth
H
,
Dowling
JJ
,
Ferreiro
A
,
Muntoni
F
;
RYR1 Myopathy Consortium
:
217th ENMC International Workshop: RYR1-related myopathies, Naarden, The Netherlands, 29–31 January 2016.
Neuromuscul Disord
2016
;
26
:
624
33
5.
Litman
RS
,
Rosenberg
H
:
Malignant hyperthermia: Update on susceptibility testing.
JAMA
2005
;
293
:
2918
24
6.
Riazi
S
,
Kraeva
N
,
Muldoon
SM
,
Dowling
J
,
Ho
C
,
Petre
MA
,
Parness
J
,
Dirksen
RT
,
Rosenberg
H
:
Malignant hyperthermia and the clinical significance of type-1 ryanodine receptor gene (RYR1) variants: Proceedings of the 2013 MHAUS Scientific Conference.
Can J Anaesth
2014
;
61
:
1040
9
7.
Murayama
T
,
Kurebayashi
N
,
Ogawa
H
,
Yamazawa
T
,
Oyamada
H
,
Suzuki
J
,
Kanemaru
K
,
Oguchi
K
,
Iino
M
,
Sakurai
T
:
Genotype-phenotype correlations of malignant hyperthermia and central core disease mutations in the central region of the RYR1 channel.
Hum Mutat
2016
;
37
:
1231
41
8.
European Malignant Hypothermia Group
:
CACNA1S mutations.
Available at: https://emhg.org/genetics/mutations-in-ryr1/. Accessed August 20, 2017
.
9.
Dowling
JJ
,
Lawlor
MW
,
Dirksen
RT
:
Triadopathies: An emerging class of skeletal muscle diseases.
Neurotherapeutics
2014
;
11
:
773
85
10.
Snoeck
M
,
van Engelen
BG
,
Küsters
B
,
Lammens
M
,
Meijer
R
,
Molenaar
JP
,
Raaphorst
J
,
Verschuuren-Bemelmans
CC
,
Straathof
CS
,
Sie
LT
,
de Coo
IF
,
van der Pol
WL
,
de Visser
M
,
Scheffer
H
,
Treves
S
,
Jungbluth
H
,
Voermans
NC
,
Kamsteeg
EJ
:
RYR1-related myopathies: A wide spectrum of phenotypes throughout life.
Eur J Neurol
2015
;
22
:
1094
112
11.
Bamaga
AK
,
Riazi
S
,
Amburgey
K
,
Ong
S
,
Halliday
W
,
Diamandis
P
,
Guerguerian
AM
,
Dowling
JJ
,
Yoon
G
:
Neuromuscular conditions associated with malignant hyperthermia in paediatric patients: A 25-year retrospective study.
Neuromuscul Disord
2016
;
26
:
201
6
12.
Amburgey
K
,
Bailey
A
,
Hwang
JH
,
Tarnopolsky
MA
,
Bonnemann
CG
,
Medne
L
,
Mathews
KD
,
Collins
J
,
Daube
JR
,
Wellman
GP
,
Callaghan
B
,
Clarke
NF
,
Dowling
JJ
:
Genotype-phenotype correlations in recessive RYR1-related myopathies.
Orphanet J Rare Dis
2013
;
8
:
117
13.
Allen
GC
,
Larach
MG
,
Kunselman
AR
:
The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States: The sensitivity and specificity of the caffeine-halothane contracture test: A report from the North American Malignant Hyperthermia Registry.
Anesthesiology
1998
;
88
:
579
88
14.
Hopkins
PM
,
Rüffert
H
,
Snoeck
MM
,
Girard
T
,
Glahn
KP
,
Ellis
FR
,
Müller
CR
,
Urwyler
A
;
European Malignant Hyperthermia Group
:
European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility.
Br J Anaesth
2015
;
115
:
531
9
15.
Allen
GC
,
Rosenberg
H
,
Fletcher
JE
:
Safety of general anesthesia in patients previously tested negative for malignant hyperthermia susceptibility.
Anesthesiology
1990
;
72
:
619
22
16.
Pollock
N
,
Langton
EE
,
Stowell
KM
,
Bulger
TF
:
Safety of exposure of malignant hyperthermia non-susceptible patients and their relatives to anaesthetic triggering agents.
Anaesth Intensive Care
2011
;
39
:
887
94
17.
Avila
G
,
Dirksen
RT
:
Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor.
J Gen Physiol
2001
;
118
:
277
90
18.
Avila
G
,
O’Brien
JJ
,
Dirksen
RT
:
Excitation–contraction uncoupling by a human central core disease mutation in the ryanodine receptor.
Proc Natl Acad Sci U S A
2001
;
98
:
4215
20
19.
Larach
MG
,
Gronert
GA
,
Allen
GC
,
Brandom
BW
,
Lehman
EB
:
Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006.
Anesth Analg
2010
;
110
:
498
507
20.
Riazi
S
,
Larach
MG
,
Hu
C
,
Wijeysundera
D
,
Massey
C
,
Kraeva
N
:
Malignant hyperthermia in Canada: Characteristics of index anesthetics in 129 malignant hyperthermia susceptible probands.
Anesth Analg
2014
;
118
:
381
7
21.
Nelson
P
,
Litman
RS
:
Malignant hyperthermia in children: An analysis of the North American malignant hyperthermia registry.
Anesth Analg
2014
;
118
:
369
74
22.
Poussel
M
,
Guerci
P
,
Kaminsky
P
,
Heymonet
M
,
Roux-Buisson
N
,
Faure
J
,
Fronzaroli
E
,
Chenuel
B
:
Exertional heat stroke and susceptibility to malignant hyperthermia in an athlete: Evidence for a link?
J Athl Train
2015
;
50
:
1212
4
23.
Köchling
A
,
Wappler
F
,
Winkler
G
,
Schulte am Esch
JS
:
Rhabdomyolysis following severe physical exercise in a patient with predisposition to malignant hyperthermia.
Anaesth Intensive Care
1998
;
26
:
315
8
24.
Capacchione
JF
,
Muldoon
SM
:
The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia.
Anesth Analg
2009
;
109
:
1065
9
25.
Sambuughin
N
,
Capacchione
J
,
Blokhin
A
,
Bayarsaikhan
M
,
Bina
S
,
Muldoon
S
:
The ryanodine receptor type 1 gene variants in African American men with exertional rhabdomyolysis and malignant hyperthermia susceptibility.
Clin Genet
2009
;
76
:
564
8
26.
Wappler
F
,
Fiege
M
,
Steinfath
M
,
Agarwal
K
,
Scholz
J
,
Singh
S
,
Matschke
J
,
Schulte Am Esch
J
:
Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis.
Anesthesiology
2001
;
94
:
95
100
27.
Muldoon
S
,
Deuster
P
,
Voelkel
M
,
Capacchione
J
,
Bunger
R
:
Exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia: Is there a link?
Curr Sports Med Rep
2008
;
7
:
74
80
28.
Sagui
E
,
Montigon
C
,
Abriat
A
,
Jouvion
A
,
Duron-Martinaud
S
,
Canini
F
,
Zagnoli
F
,
Bendahan
D
,
Figarella-Branger
D
,
Brégigeon
M
,
Brosset
C
:
Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia?
PLoS One
2015
;
10
:
e0135496
29.
Krivosic-Horber
R
,
Dépret
T
,
Wagner
JM
,
Maurage
CA
:
Malignant hyperthermia susceptibility revealed by increased serum creatine kinase concentrations during statin treatment.
Eur J Anaesthesiol
2004
;
21
:
572
4
30.
Roux-Buisson
N
,
Monnier
N
,
Sagui
E
,
Abriat
A
,
Brosset
C
,
Bendahan
D
,
Kozak-Ribbens
G
,
Gazzola
S
,
Quesada
JL
,
Foutrier-Morello
C
,
Rendu
J
,
Figarella-Branger
D
,
Cozonne
P
,
Aubert
M
,
Bourdon
L
,
Lunardi
J
,
Fauré
J
:
Identification of variants of the ryanodine receptor type 1 in patients with exertional heat stroke and positive response to the malignant hyperthermia in vitro contracture test.
Br J Anaesth
2016
;
116
:
566
8
31.
Molenaar
JP
,
Voermans
NC
,
van Hoeve
BJ
,
Kamsteeg
EJ
,
Kluijtmans
LA
,
Kusters
B
,
Jungbluth
HJ
,
van Engelen
BG
:
Fever-induced recurrent rhabdomyolysis due to a novel mutation in the ryanodine receptor type 1 gene.
Intern Med J
2014
;
44
:
819
20
32.
Dlamini
N
,
Voermans
NC
,
Lillis
S
,
Stewart
K
,
Kamsteeg
EJ
,
Drost
G
,
Quinlivan
R
,
Snoeck
M
,
Norwood
F
,
Radunovic
A
,
Straub
V
,
Roberts
M
,
Vrancken
AF
,
van der Pol
WL
,
de Coo
RI
,
Manzur
AY
,
Yau
S
,
Abbs
S
,
King
A
,
Lammens
M
,
Hopkins
PM
,
Mohammed
S
,
Treves
S
,
Muntoni
F
,
Wraige
E
,
Davis
MR
,
van Engelen
B
,
Jungbluth
H
:
Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis.
Neuromuscul Disord
2013
;
23
:
540
8
33.
Lopez
RJ
,
Byrne
S
,
Vukcevic
M
,
Sekulic-Jablanovic
M
,
Xu
L
,
Brink
M
,
Alamelu
J
,
Voermans
N
,
Snoeck
M
,
Clement
E
,
Muntoni
F
,
Zhou
H
,
Radunovic
A
,
Mohammed
S
,
Wraige
E
,
Zorzato
F
,
Treves
S
,
Jungbluth
H
:
An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities.
Sci Signal
2016
;
9
:
ra68
34.
Hedenmalm
K
,
Granberg
AG
,
Dahl
ML
:
Statin-induced muscle toxicity and susceptibility to malignant hyperthermia and other muscle diseases: A population-based case-control study including 1st and 2nd degree relatives.
Eur J Clin Pharmacol
2015
;
71
:
117
24
35.
Hopkins
PM
:
Is there a link between malignant hyperthermia and exertional heat illness?
Br J Sports Med
2007
;
41
:
283
4
36.
Weglinski
MR
,
Wedel
DJ
,
Engel
AG
:
Malignant hyperthermia testing in patients with persistently increased serum creatine kinase levels.
Anesth Analg
1997
;
84
:
1038
41
37.
Malandrini
A
,
Orrico
A
,
Gaudiano
C
,
Gambelli
S
,
Galli
L
,
Berti
G
,
Tegazzin
V
,
Dotti
MT
,
Federico
A
,
Sorrentino
V
:
Muscle biopsy and in vitro contracture test in subjects with idiopathic HyperCKemia.
Anesthesiology
2008
;
109
:
625
8
38.
Groom
L
,
Muldoon
SM
,
Tang
ZZ
,
Brandom
BW
,
Bayarsaikhan
M
,
Bina
S
,
Lee
HS
,
Qiu
X
,
Sambuughin
N
,
Dirksen
RT
:
Identical de novo mutation in the type 1 ryanodine receptor gene associated with fatal, stress-induced malignant hyperthermia in two unrelated families.
Anesthesiology
2011
;
115
:
938
45
39.
Bharucha-Goebel
DX
,
Santi
M
,
Medne
L
,
Zukosky
K
,
Zukosky
K
,
Dastgir
J
,
Shieh
PB
,
Winder
T
,
Tennekoon
G
,
Finkel
RS
,
Dowling
JJ
,
Monnier
N
,
Bönnemann
CG
:
Severe congenital RYR1-associated myopathy: The expanding clinicopathologic and genetic spectrum.
Neurology
2013
;
80
:
1584
9
40.
Brislin
RP
,
Theroux
MC
:
Core myopathies and malignant hyperthermia susceptibility: A review.
Paediatr Anaesth
2013
;
23
:
834
41
41.
Klingler
W
,
Rueffert
H
,
Lehmann-Horn
F
,
Girard
T
,
Hopkins
PM
:
Core myopathies and risk of malignant hyperthermia.
Anesth Analg
2009
;
109
:
1167
73
42.
Taylor
A
,
Lachlan
K
,
Manners
RM
,
Lotery
AJ
:
A study of a family with the skeletal muscle RYR1 mutation (c.7354C>T) associated with central core myopathy and malignant hyperthermia susceptibility.
J Clin Neurosci
2012
;
19
:
65
70
43.
Jungbluth
H
,
Zhou
H
,
Hartley
L
,
Halliger-Keller
B
,
Messina
S
,
Longman
C
,
Brockington
M
,
Robb
SA
,
Straub
V
,
Voit
T
,
Swash
M
,
Ferreiro
A
,
Bydder
G
,
Sewry
CA
,
Müller
C
,
Muntoni
F
:
Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.
Neurology
2005
;
65
:
1930
5
44.
Kaplan
JC
,
Hamroun
D
:
The 2015 version of the gene table of monogenic neuromuscular disorders (nuclear genome).
Neuromuscul Disord
2014
;
24
:
1123
53
45.
Mathews
KD
,
Moore
SA
:
Multiminicore myopathy, central core disease, malignant hyperthermia susceptibility, and RYR1 mutations: One disease with many faces?
Arch Neurol
2004
;
61
:
27
9
46.
Monnier
N
,
Romero
NB
,
Lerale
J
,
Nivoche
Y
,
Qi
D
,
MacLennan
DH
,
Fardeau
M
,
Lunardi
J
:
An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor.
Hum Mol Genet
2000
;
9
:
2599
608
47.
Kraeva
N
,
Heytens
L
,
Jungbluth
H
,
Treves
S
,
Voermans
N
,
Kamsteeg
E
,
Ceuterick-de Groote
C
,
Baets
J
,
Riazi
S
:
Compound RYR1 heterozygosity resulting in a complex phenotype of malignant hyperthermia susceptibility and a core myopathy.
Neuromuscul Disord
2015
;
25
:
567
76
48.
Wilmshurst
JM
,
Lillis
S
,
Zhou
H
,
Pillay
K
,
Henderson
H
,
Kress
W
,
Müller
CR
,
Ndondo
A
,
Cloke
V
,
Cullup
T
,
Bertini
E
,
Boennemann
C
,
Straub
V
,
Quinlivan
R
,
Dowling
JJ
,
Al-Sarraj
S
,
Treves
S
,
Abbs
S
,
Manzur
AY
,
Sewry
CA
,
Muntoni
F
,
Jungbluth
H
:
RYR1 mutations are a common cause of congenital myopathies with central nuclei.
Ann Neurol
2010
;
68
:
717
26
49.
Clarke
NF
,
Waddell
LB
,
Cooper
ST
,
Perry
M
,
Smith
RL
,
Kornberg
AJ
,
Muntoni
F
,
Lillis
S
,
Straub
V
,
Bushby
K
,
Guglieri
M
,
King
MD
,
Farrell
MA
,
Marty
I
,
Lunardi
J
,
Monnier
N
,
North
KN
:
Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.
Hum Mutat
2010
;
31
:
E1544
50
50.
Dowling
JJ
,
Lillis
S
,
Amburgey
K
,
Zhou
H
,
Al-Sarraj
S
,
Buk
SJ
,
Wraige
E
,
Chow
G
,
Abbs
S
,
Leber
S
,
Lachlan
K
,
Baralle
D
,
Taylor
A
,
Sewry
C
,
Muntoni
F
,
Jungbluth
H
:
King–Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.
Neuromuscul Disord
2011
;
21
:
420
7
51.
D’Arcy
CE
,
Bjorksten
A
,
Yiu
EM
,
Bankier
A
,
Gillies
R
,
McLean
CA
,
Shield
LK
,
Ryan
MM
:
King–Denborough syndrome caused by a novel mutation in the ryanodine receptor gene.
Neurology
2008
;
71
:
776
7
52.
Heiman-Patterson
TD
,
Rosenberg
HR
,
Binning
CP
,
Tahmoush
AJ
:
King–Denborough syndrome: Contracture testing and literature review.
Pediatr Neurol
1986
;
2
:
175
7
53.
Joseph
MR
,
Theroux
MC
,
Mooney
JJ
,
Falitz
S
,
Brandom
BW
,
Byler
DL
:
Intraoperative presentation of malignant hyperthermia (confirmed by RYR1 gene mutation, c.7522C>T; p.R2508C) leads to diagnosis of King–Denborough syndrome in a child with hypotonia and dysmorphic features: A case report.
A A Case Rep
2017
;
8
:
55
7
54.
Kondo
E
,
Nishimura
T
,
Kosho
T
,
Inaba
Y
,
Mitsuhashi
S
,
Ishida
T
,
Baba
A
,
Koike
K
,
Nishino
I
,
Nonaka
I
,
Furukawa
T
,
Saito
K
:
Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing.
Am J Med Genet A
2012
;
158A
:
772
8
55.
Gronert
GA
,
Theye
RA
:
Pathophysiology of hyperkalemia induced by succinylcholine.
Anesthesiology
1975
;
43
:
89
99
56.
Gurnaney
H
,
Brown
A
,
Litman
RS
:
Malignant hyperthermia and muscular dystrophies.
Anesth Analg
2009
;
109
:
1043
8
57.
Monnier
N
,
Krivosic-Horber
R
,
Payen
JF
,
Kozak-Ribbens
G
,
Nivoche
Y
,
Adnet
P
,
Reyford
H
,
Lunardi
J
:
Presence of two different genetic traits in malignant hyperthermia families: Implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility.
Anesthesiology
2002
;
97
:
1067
74
58.
Monnier
N
,
Procaccio
V
,
Stieglitz
P
,
Lunardi
J
:
Malignant-hyperthermia susceptibility is associated with a mutation of the α1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle.
Am J Hum Genet
1997
;
60
:
1316
25
59.
Toppin
PJ
,
Chandy
TT
,
Ghanekar
A
,
Kraeva
N
,
Beattie
WS
,
Riazi
S
:
A report of fulminant malignant hyperthermia in a patient with a novel mutation of the CACNA1S gene.
Can J Anaesth
2010
;
57
:
689
93
60.
Hunter
JM
,
Ahearn
ME
,
Balak
CD
,
Liang
WS
,
Kurdoglu
A
,
Corneveaux
JJ
,
Russell
M
,
Huentelman
MJ
,
Craig
DW
,
Carpten
J
,
Coons
SW
,
DeMello
DE
,
Hall
JG
,
Bernes
SM
,
Baumbach-Reardon
L
:
Novel pathogenic variants and genes for myopathies identified by whole exome sequencing.
Mol Genet Genomic Med
2015
;
3
:
283
301
61.
Schartner
V
,
Romero
NB
,
Donkervoort
S
,
Treves
S
,
Munot
P
,
Pierson
TM
,
Dabaj
I
,
Malfatti
E
,
Zaharieva
IT
,
Zorzato
F
,
Abath Neto
O
,
Brochier
G
,
Lornage
X
,
Eymard
B
,
Taratuto
AL
,
Böhm
J
,
Gonorazky
H
,
Ramos-Platt
L
,
Feng
L
,
Phadke
R
,
Bharucha-Goebel
DX
,
Sumner
CJ
,
Bui
MT
,
Lacene
E
,
Beuvin
M
,
Labasse
C
,
Dondaine
N
,
Schneider
R
,
Thompson
J
,
Boland
A
,
Deleuze
JF
,
Matthews
E
,
Pakleza
AN
,
Sewry
CA
,
Biancalana
V
,
Quijano-Roy
S
,
Muntoni
F
,
Fardeau
M
,
Bönnemann
CG
,
Laporte
J
:
Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy.
Acta Neuropathol
2017
;
133
:
517
33
62.
Marchant
CL
,
Ellis
FR
,
Halsall
PJ
,
Hopkins
PM
,
Robinson
RL
:
Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia.
Muscle Nerve
2004
;
30
:
114
7
63.
Rajabally
YA
,
El Lahawi
M
:
Hypokalemic periodic paralysis associated with malignant hyperthermia.
Muscle Nerve
2002
;
25
:
453
5
64.
Bulman
DE
,
Scoggan
KA
,
van Oene
MD
,
Nicolle
MW
,
Hahn
AF
,
Tollar
LL
,
Ebers
GC
:
A novel sodium channel mutation in a family with hypokalemic periodic paralysis.
Neurology
1999
;
53
:
1932
6
65.
Sternberg
D
,
Maisonobe
T
,
Jurkat-Rott
K
,
Nicole
S
,
Launay
E
,
Chauveau
D
,
Tabti
N
,
Lehmann-Horn
F
,
Hainque
B
,
Fontaine
B
:
Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A.
Brain
2001
;
124
:
1091
9
66.
Stamm
DS
,
Aylsworth
AS
,
Stajich
JM
,
Kahler
SG
,
Thorne
LB
,
Speer
MC
,
Powell
CM
:
Native American myopathy: Congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia.
Am J Med Genet A
2008
;
146A
:
1832
41
67.
Stamm
DS
,
Powell
CM
,
Stajich
JM
,
Zismann
VL
,
Stephan
DA
,
Chesnut
B
,
Aylsworth
AS
,
Kahler
SG
,
Deak
KL
,
Gilbert
JR
,
Speer
MC
:
Novel congenital myopathy locus identified in Native American Indians at 12q13.13–14.1.
Neurology
2008
;
71
:
1764
9
68.
Bailey
AG
,
Bloch
EC
:
Malignant hyperthermia in a three-month-old American Indian infant.
Anesth Analg
1987
;
66
:
1043
5
69.
Larach
MG
,
Rosenberg
H
,
Gronert
GA
,
Allen
GC
:
Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies.
Clin Pediatr (Phila)
1997
;
36
:
9
16
70.
Boba
A
:
Fatal postanesthetic complications in two muscular dystrophic patients.
J Pediatr Surg
1970
;
5
:
71
5
71.
Kelfer
HM
,
Singer
WD
,
Reynolds
RN
:
Malignant hyperthermia in a child with Duchenne muscular dystrophy.
Pediatrics
1983
;
71
:
118
9
72.
Sethna
NF
,
Rockoff
MA
:
Cardiac arrest following inhalation induction of anaesthesia in a child with Duchenne’s muscular dystrophy.
Can Anaesth Soc J
1986
;
33
:
799
802
73.
Rubiano
R
,
Chang
JL
,
Carroll
J
,
Sonbolian
N
,
Larson
CE
:
Acute rhabdomyolysis following halothane anesthesia without succinylcholine.
Anesthesiology
1987
;
67
:
856
7
74.
Marks
WA
,
Bodensteiner
JB
,
Reitz
RD
:
Cardiac arrest during anesthetic induction in a child with Becker type muscular dystrophy.
J Child Neurol
1987
;
2
:
160
1
75.
Poole
TC
,
Lim
TY
,
Buck
J
,
Kong
AS
:
Perioperative cardiac arrest in a patient with previously undiagnosed Becker’s muscular dystrophy after isoflurane anaesthesia for elective surgery.
Br J Anaesth
2010
;
104
:
487
9
76.
Flick
RP
,
Gleich
SJ
,
Herr
MM
,
Wedel
DJ
:
The risk of malignant hyperthermia in children undergoing muscle biopsy for suspected neuromuscular disorder.
Paediatr Anaesth
2007
;
17
:
22
7
77.
Shapiro
F
,
Athiraman
U
,
Clendenin
DJ
,
Hoagland
M
,
Sethna
NF
:
Anesthetic management of 877 pediatric patients undergoing muscle biopsy for neuromuscular disorders: A 20-year review.
Paediatr Anaesth
2016
;
26
:
710
21
78.
Hayes
J
,
Veyckemans
F
,
Bissonnette
B
:
Duchenne muscular dystrophy: An old anesthesia problem revisited.
Paediatr Anaesth
2008
;
18
:
100
6
79.
Yemen
TA
,
McClain
C
:
Muscular dystrophy, anesthesia and the safety of inhalational agents revisited; again.
Paediatr Anaesth
2006
;
16
:
105
8
80.
Birnkrant
DJ
:
The American College of Chest Physicians consensus statement on the respiratory and related management of patients with Duchenne muscular dystrophy undergoing anesthesia or sedation.
Pediatrics
2009
;
123
(
Suppl 4
):
S242
4
81.
American Academy of Pediatrics Section on C, Cardiac S
:
Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy.
Pediatrics
2005
;
116
:
1569
73
82.
Irwin
MG
,
Henderson
M
:
Cardiac arrest during major spinal scoliosis surgery in a patient with Duchenne’s muscular dystrophy undergoing intravenous anaesthesia.
Anaesth Intensive Care
1995
;
23
:
626
9
83.
Schmidt
GN
,
Burmeister
MA
,
Lilje
C
,
Wappler
F
,
Bischoff
P
:
Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy.
Br J Anaesth
2003
;
90
:
800
4
84.
Segura
LG
,
Lorenz
JD
,
Weingarten
TN
,
Scavonetto
F
,
Bojanić
K
,
Selcen
D
,
Sprung
J
:
Anesthesia and Duchenne or Becker muscular dystrophy: Review of 117 anesthetic exposures.
Paediatr Anaesth
2013
;
23
:
855
64
85.
Wieser
T
,
Kraft
B
,
Kress
HG
:
No carnitine palmitoyltransferase deficiency in skeletal muscle in 18 malignant hyperthermia susceptible individuals.
Neuromuscul Disord
2008
;
18
:
471
4
86.
Hogan
KJ
,
Vladutiu
GD
:
Malignant hyperthermia-like syndrome and carnitine palmitoyltransferase II deficiency with heterozygous R503C mutation.
Anesth Analg
2009
;
109
:
1070
2
87.
Shukry
M
,
Guruli
ZV
,
Ramadhyani
U
:
Suspected malignant hyperthermia in a child with laminin α2 (merosin) deficiency in the absence of a triggering agent.
Paediatr Anaesth
2006
;
16
:
462
5
88.
Scrivener
TA
,
Ross
SM
,
Street
NE
,
Webster
RI
,
De Lima
JC
:
A case series of general anesthesia in children with laminin α2 (merosin)-deficient congenital muscular dystrophy.
Paediatr Anaesth
2014
;
24
:
464
5
89.
Fricker
RM
,
Raffelsberger
T
,
Rauch-Shorny
S
,
Finsterer
J
,
Müller-Reible
C
,
Gilly
H
,
Bittner
RE
:
Positive malignant hyperthermia susceptibility in vitro test in a patient with mitochondrial myopathy and myoadenylate deaminase deficiency.
Anesthesiology
2002
;
97
:
1635
7
90.
Benca
J
,
Hogan
K
:
Malignant hyperthermia, coexisting disorders, and enzymopathies: Risks and management options.
Anesth Analg
2009
;
109
:
1049
53
91.
Ghert
M
,
Allen
B
,
Davids
J
,
Stasikelis
P
,
Nicholas
D
:
Increased postoperative febrile response in children with osteogenesis imperfecta.
J Pediatr Orthop
2003
;
23
:
261
4
92.
Ryan
CA
,
Al-Ghamdi
AS
,
Gayle
M
,
Finer
NN
:
Osteogenesis imperfecta and hyperthermia.
Anesth Analg
1989
;
68
:
811
4
93.
Porsborg
P
,
Astrup
G
,
Bendixen
D
,
Lund
AM
,
Ording
H
:
Osteogenesis imperfecta and malignant hyperthermia: Is there a relationship?
Anaesthesia
1996
;
51
:
863
5
94.
Gleich
SJ
,
Tien
M
,
Schroeder
DR
,
Hanson
AC
,
Flick
R
,
Nemergut
ME
:
Anesthetic outcomes of children with arthrogryposis syndromes: No evidence of hyperthermia.
Anesth Analg
2017
;
124
:
908
14
95.
Witherspoon
JW
,
Meilleur
KG
:
Review of RyR1 pathway and associated pathomechanisms.
Acta Neuropathol Commun
2016
;
4
:
121
96.
Peredo
DE
,
Hannibal
MC
:
The floppy infant: Evaluation of hypotonia.
Pediatr Rev
2009
;
30
:
e66
76
97.
O’Grady
GL
,
Lek
M
,
Lamande
SR
,
Waddell
L
,
Oates
EC
,
Punetha
J
,
Ghaoui
R
,
Sandaradura
SA
,
Best
H
,
Kaur
S
,
Davis
M
,
Laing
NG
,
Muntoni
F
,
Hoffman
E
,
MacArthur
DG
,
Clarke
NF
,
Cooper
S
,
North
K
:
Diagnosis and etiology of congenital muscular dystrophy: We are halfway there.
Ann Neurol
2016
;
80
:
101
11
98.
Odermatt
A
,
Taschner
PE
,
Khanna
VK
,
Busch
HF
,
Karpati
G
,
Jablecki
CK
,
Breuning
MH
,
MacLennan
DH
:
Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease.
Nat Genet
1996
;
14
:
191
4
99.
Sambuughin
N
,
Zvaritch
E
,
Kraeva
N
,
Sizova
O
,
Sivak
E
,
Dickson
K
,
Weglinski
M
,
Capacchione
J
,
Muldoon
S
,
Riazi
S
,
Hamilton
S
,
Brandom
B
,
MacLennan
DH
:
Exome analysis identifies Brody myopathy in a family diagnosed with malignant hyperthermia susceptibility.
Mol Genet Genomic Med
2014
;
2
:
472
83