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MCID: MLG147
MIFTS: 36

Malignant Hyperthermia 1

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Fetal diseases
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Drugs
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Aliases & Classifications for Malignant Hyperthermia 1

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MalaCards integrated aliases for Malignant Hyperthermia 1:

Name: Malignant Hyperthermia 1 57 75
King Denborough Syndrome 53 29 6 73
Malignant Hyperthermia, Susceptibility to, 1 57 29 6
Malignant Hyperthermia Susceptibility Type 1 76 53 73
Mhs1 57 53 75
Malignant Hyperthermia Susceptibility 1 57 13
Hyperthermia of Anesthesia 57 53
King-Denborough Syndrome 57 59
Hyperpyrexia, Malignant 57 53
Mhs 57 53
Anesthetic-Induced Malignant Hyperpyrexia in Children 53
Hyperthermia, Malignant, Susceptibility, Type 1 40
Malignant Hyperpyrexia Due to Anesthesia 73
Hyperpyrexia, Malignant; Mh 57
Koussef-Nichols Syndrome 59
King Syndrome 53
Mh 57

Characteristics:

Orphanet epidemiological data:

59
king-denborough syndrome
Inheritance: Autosomal dominant;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
heterogeneous disorder
precipitated by general anesthesia
elevated body temperatures to 42 degrees celsius
incidence of mh in anesthetized children is 1 in 15,000
incidence of mh in anesthetized adults is 1 in 50,000-100,000


HPO:

32
malignant hyperthermia 1:
Inheritance autosomal dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 34
Orphanet: 59  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM 57 145600
Orphanet 59 ORPHA99741
UMLS via Orphanet 74 C1840365
ICD10 via Orphanet 34 G71.2
MESH via Orphanet 45 C536883
Sources

Summaries for Malignant Hyperthermia 1

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UniProtKB/Swiss-Prot : 75 Malignant hyperthermia 1: Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively).

MalaCards based summary : Malignant Hyperthermia 1, also known as king denborough syndrome, is related to malignant hyperthermia of anesthesia and central core disease of muscle, and has symptoms including fever, muscle rigidity and pain, postoperative. An important gene associated with Malignant Hyperthermia 1 is RYR1 (Ryanodine Receptor 1). Affiliated tissues include skeletal muscle, testes and heart, and related phenotypes are tachycardia and fever

OMIM : 57 Malignant hyperthermia susceptibility (MHS), a skeletal muscle disorder most often inherited as an autosomal dominant trait, is one of the main causes of death due to anesthesia. In susceptible people, a malignant hyperthermia episode is triggered by exposure to commonly used volatile anesthetic agents such as halothane or depolarizing muscle relaxants such as succinyl choline. A fulminant MH crisis is characterized by any combination of hyperthermia, skeletal muscle rigidity, tachycardia or arrhythmia, respiratory and metabolic acidosis, and rhabdomyolysis. Except for this susceptibility to triggering agents, MHS patients are not clinically distinguishable from the general population (summary by Monnier et al., 1997). (145600)

NIH Rare Diseases : 53 The King-Denborough syndrome (KDS) is a congenital myopathy associated with susceptibility to malignant hyperthermia, skeletal abnormalities and dysmorphic features with characteristic facial appearance. Although the cause of King-Denborough syndrome is not fully understood, at least some cases have been attributed to the ryanodine receptor gene (RYR1), which has been tied to malignant hyperthermia and central core disease.

Wikipedia : 76 Malignant hyperthermia (MH) is a type of severe reaction that occurs to particular medications used... more...

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Related Diseases for Malignant Hyperthermia 1

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Diseases in the Malignant Hyperthermia family:

Malignant Hyperthermia 1 Malignant Hyperthermia 2
Malignant Hyperthermia 3 Malignant Hyperthermia 4
Malignant Hyperthermia 5 Malignant Hyperthermia 6

Diseases related to Malignant Hyperthermia 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 malignant hyperthermia of anesthesia 12.2
2 central core disease of muscle 11.0
3 malignant hyperthermia 10.0
4 cleft palate, isolated 9.6

Sources

Symptoms & Phenotypes for Malignant Hyperthermia 1

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Symptoms via clinical synopsis from OMIM:

57
Cardiovascular Vascular:
hypotension

Cardiovascular Heart:
tachycardia
cardiac arrhythmias

Neurologic Central Nervous System:
hyperthermia

Hematology:
coagulopathy

Laboratory Abnormalities:
hyperkalemia
hyperphosphatemia
myoglobinuria
elevated serum cpk
diagnosis by exposing muscle biopsy to caffeine and/or halothane

Muscle Soft Tissue:
rhabdomyolysis
muscle rigidity

Metabolic Features:
mixed respiratory and metabolic acidosis


Clinical features from OMIM:

145600

Human phenotypes related to Malignant Hyperthermia 1:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 tachycardia 32 HP:0001649
2 fever 32 HP:0001945
3 malignant hyperthermia 32 HP:0002047
4 rigidity 32 HP:0002063
5 hyperkalemia 32 HP:0002153
6 hypotension 32 HP:0002615
7 hyperphosphatemia 32 HP:0002905
8 myoglobinuria 32 HP:0002913
9 rhabdomyolysis 32 HP:0003201
10 elevated serum creatine phosphokinase 32 HP:0003236
11 abnormality of the coagulation cascade 32 HP:0003256
12 mixed respiratory and metabolic acidosis 32 HP:0005967

UMLS symptoms related to Malignant Hyperthermia 1:


fever, muscle rigidity, pain, postoperative, postoperative nausea and vomiting
Sources

Drugs & Therapeutics for Malignant Hyperthermia 1

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Search Clinical Trials , NIH Clinical Center for Malignant Hyperthermia 1

Inferred drug relations via UMLS 73 / NDF-RT 51 :
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Genetic Tests for Malignant Hyperthermia 1

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Genetic tests related to Malignant Hyperthermia 1:

# Genetic test Affiliating Genes
1 Malignant Hyperthermia, Susceptibility to, 1 29 RYR1
2 King Denborough Syndrome 29
Sources

Anatomical Context for Malignant Hyperthermia 1

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MalaCards organs/tissues related to Malignant Hyperthermia 1:

41
Skeletal Muscle, Testes, Heart
Sources

Publications for Malignant Hyperthermia 1

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Articles related to Malignant Hyperthermia 1:

# Title Authors Year
1
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. ( 27918309 )
2016
2
King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene. ( 21514828 )
2011
3
King-denborough syndrome caused by a novel mutation in the ryanodine receptor gene. ( 18765655 )
2008
4
Anesthetic management of a ventilator-dependent parturient with the King-Denborough syndrome. ( 12826552 )
2003
5
King-Denborough Syndrome: report of two Brazilian cases. ( 12364941 )
2002
6
Dominantly inherited malignant hyperthermia (MH) in the King-Denborough syndrome. ( 1508238 )
1992
7
King-Denborough syndrome: contracture testing and literature review. ( 2907859 )
1986
Sources

Variations for Malignant Hyperthermia 1

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UniProtKB/Swiss-Prot genetic disease variations for Malignant Hyperthermia 1:

75 (show top 50) (show all 93)
# Symbol AA change Variation ID SNP ID
1 RYR1 p.Cys35Arg VAR_005589 rs193922747
2 RYR1 p.Arg163Cys VAR_005590 rs118192161
3 RYR1 p.Gly341Arg VAR_005592 rs121918592
4 RYR1 p.Ile403Met VAR_005593 rs118192116
5 RYR1 p.Tyr522Ser VAR_005595 rs118192162
6 RYR1 p.Arg552Trp VAR_005596 rs193922770
7 RYR1 p.Arg614Cys VAR_005597 rs118192172
8 RYR1 p.Arg614Leu VAR_005598 rs193922772
9 RYR1 p.Arg2163Cys VAR_005601 rs118192175
10 RYR1 p.Arg2163His VAR_005602 rs118192163
11 RYR1 p.Val2168Met VAR_005603 rs118192176
12 RYR1 p.Thr2206Met VAR_005604 rs118192177
13 RYR1 p.Gly2434Arg VAR_005605 rs121918593
14 RYR1 p.Arg2435His VAR_005606 rs28933396
15 RYR1 p.Arg533His VAR_008971 rs144336148
16 RYR1 p.Arg2163Pro VAR_008972 rs118192163
17 RYR1 p.Thr2206Arg VAR_008973 rs118192177
18 RYR1 p.Arg2435Leu VAR_008974 rs28933396
19 RYR1 p.Arg2454Cys VAR_008975 rs193922816
20 RYR1 p.Arg2454His VAR_008976 rs118192122
21 RYR1 p.Arg2458Cys VAR_008977 rs28933397
22 RYR1 p.Arg2458His VAR_008978 rs121918594
23 RYR1 p.Arg44Cys VAR_045695 rs193922748
24 RYR1 p.Arg163Leu VAR_045697 rs193922753
25 RYR1 p.Gly165Arg VAR_045698 rs193922754
26 RYR1 p.Asp166Asn VAR_045699 rs193922755
27 RYR1 p.Arg177Cys VAR_045700 rs193922757
28 RYR1 p.Tyr178Cys VAR_045701
29 RYR1 p.Asp227Val VAR_045703 rs193922760
30 RYR1 p.Arg328Trp VAR_045704 rs193922762
31 RYR1 p.Arg401Cys VAR_045705 rs193922764
32 RYR1 p.Arg401His VAR_045706 rs193922766
33 RYR1 p.Arg401Ser VAR_045707
34 RYR1 p.Arg533Cys VAR_045708 rs193922768
35 RYR1 p.Val2117Leu VAR_045712 rs193922788
36 RYR1 p.Asp2129Glu VAR_045713 rs117886618
37 RYR1 p.Val2214Ile VAR_045714 rs193922795
38 RYR1 p.Val2280Ile VAR_045715 rs193922797
39 RYR1 p.Asn2342Ser VAR_045716 rs147213895
40 RYR1 p.Val2346Met VAR_045718 rs193922799
41 RYR1 p.Glu2348Gly VAR_045720 rs193922801
42 RYR1 p.Ala2350Thr VAR_045721 rs193922802
43 RYR1 p.Arg2355Cys VAR_045722
44 RYR1 p.Ala2367Thr VAR_045723 rs146306934
45 RYR1 p.Ala2428Thr VAR_045725 rs193922809
46 RYR1 p.Asp2431Asn VAR_045726 rs193922810
47 RYR1 p.Ala2437Val VAR_045727 rs193922812
48 RYR1 p.Arg2452Trp VAR_045728 rs118192124
49 RYR1 p.Ile3916Met VAR_045735 rs193922840
50 RYR1 p.Arg4136Ser VAR_045736 rs193922849

ClinVar genetic disease variations for Malignant Hyperthermia 1:

6
(show top 50) (show all 201)
# Gene Variation Type Significance SNP ID Assembly Location
1 RYR1 NM_000540.2(RYR1): c.1840C> T (p.Arg614Cys) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs118192172 GRCh37 Chromosome 19, 38948185: 38948185
2 RYR1 NM_000540.2(RYR1): c.1840C> T (p.Arg614Cys) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs118192172 GRCh38 Chromosome 19, 38457545: 38457545
3 RYR1 NM_000540.2(RYR1): c.742G> A (p.Gly248Arg) single nucleotide variant risk factor rs1801086 GRCh37 Chromosome 19, 38937350: 38937350
4 RYR1 NM_000540.2(RYR1): c.742G> A (p.Gly248Arg) single nucleotide variant risk factor rs1801086 GRCh38 Chromosome 19, 38446710: 38446710
5 RYR1 NM_000540.2(RYR1): c.487C> T (p.Arg163Cys) single nucleotide variant Pathogenic rs118192161 GRCh37 Chromosome 19, 38934851: 38934851
6 RYR1 NM_000540.2(RYR1): c.487C> T (p.Arg163Cys) single nucleotide variant Pathogenic rs118192161 GRCh38 Chromosome 19, 38444211: 38444211
7 RYR1 NM_000540.2(RYR1): c.487C> T (p.Arg163Cys) single nucleotide variant Pathogenic rs118192161 NCBI36 Chromosome 19, 43626691: 43626691
8 RYR1 NM_000540.2(RYR1): c.1021G> A (p.Gly341Arg) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs121918592 GRCh37 Chromosome 19, 38939352: 38939352
9 RYR1 NM_000540.2(RYR1): c.1021G> A (p.Gly341Arg) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs121918592 GRCh38 Chromosome 19, 38448712: 38448712
10 RYR1 NM_000540.2(RYR1): c.7300G> A (p.Gly2434Arg) single nucleotide variant Pathogenic rs121918593 GRCh37 Chromosome 19, 38990633: 38990633
11 RYR1 NM_000540.2(RYR1): c.7300G> A (p.Gly2434Arg) single nucleotide variant Pathogenic rs121918593 GRCh38 Chromosome 19, 38499993: 38499993
12 RYR1 NM_000540.2(RYR1): c.7372C> T (p.Arg2458Cys) single nucleotide variant Likely pathogenic rs28933397 GRCh37 Chromosome 19, 38991294: 38991294
13 RYR1 NM_000540.2(RYR1): c.7372C> T (p.Arg2458Cys) single nucleotide variant Likely pathogenic rs28933397 GRCh38 Chromosome 19, 38500654: 38500654
14 RYR1 NM_000540.2(RYR1): c.7373G> A (p.Arg2458His) single nucleotide variant Pathogenic rs121918594 GRCh37 Chromosome 19, 38991295: 38991295
15 RYR1 NM_000540.2(RYR1): c.7373G> A (p.Arg2458His) single nucleotide variant Pathogenic rs121918594 GRCh38 Chromosome 19, 38500655: 38500655
16 RYR1 NM_000540.2(RYR1): c.6487C> T (p.Arg2163Cys) single nucleotide variant Pathogenic rs118192175 GRCh37 Chromosome 19, 38985204: 38985204
17 RYR1 NM_000540.2(RYR1): c.6487C> T (p.Arg2163Cys) single nucleotide variant Pathogenic rs118192175 GRCh38 Chromosome 19, 38494564: 38494564
18 RYR1 NM_000540.2(RYR1): c.6488G> A (p.Arg2163His) single nucleotide variant Likely pathogenic rs118192163 GRCh37 Chromosome 19, 38985205: 38985205
19 RYR1 NM_000540.2(RYR1): c.6488G> A (p.Arg2163His) single nucleotide variant Likely pathogenic rs118192163 GRCh38 Chromosome 19, 38494565: 38494565
20 RYR1 NM_000540.2(RYR1): c.14693T> C (p.Ile4898Thr) single nucleotide variant Pathogenic rs118192170 GRCh37 Chromosome 19, 39075629: 39075629
21 RYR1 NM_000540.2(RYR1): c.14693T> C (p.Ile4898Thr) single nucleotide variant Pathogenic rs118192170 GRCh38 Chromosome 19, 38584989: 38584989
22 RYR1 NM_000540.2(RYR1): c.6502G> A (p.Val2168Met) single nucleotide variant Pathogenic rs118192176 GRCh37 Chromosome 19, 38985219: 38985219
23 RYR1 NM_000540.2(RYR1): c.6502G> A (p.Val2168Met) single nucleotide variant Pathogenic rs118192176 GRCh38 Chromosome 19, 38494579: 38494579
24 RYR1 NM_000540.2(RYR1): c.6617C> T (p.Thr2206Met) single nucleotide variant Pathogenic rs118192177 GRCh37 Chromosome 19, 38986923: 38986923
25 RYR1 NM_000540.2(RYR1): c.6617C> T (p.Thr2206Met) single nucleotide variant Pathogenic rs118192177 GRCh38 Chromosome 19, 38496283: 38496283
26 RYR1 NM_000540.2(RYR1): c.14477C> T (p.Thr4826Ile) single nucleotide variant risk factor rs121918595 GRCh37 Chromosome 19, 39070734: 39070734
27 RYR1 NM_000540.2(RYR1): c.14477C> T (p.Thr4826Ile) single nucleotide variant risk factor rs121918595 GRCh38 Chromosome 19, 38580094: 38580094
28 RYR1 NM_000540.2(RYR1): c.14387A> G (p.Tyr4796Cys) single nucleotide variant Pathogenic,risk factor rs118192167 GRCh37 Chromosome 19, 39070644: 39070644
29 RYR1 NM_000540.2(RYR1): c.14387A> G (p.Tyr4796Cys) single nucleotide variant Pathogenic,risk factor rs118192167 GRCh38 Chromosome 19, 38580004: 38580004
30 RYR1 NM_000540.2(RYR1): c.1565A> C (p.Tyr522Ser) single nucleotide variant Pathogenic,risk factor rs118192162 GRCh37 Chromosome 19, 38945999: 38945999
31 RYR1 NM_000540.2(RYR1): c.1565A> C (p.Tyr522Ser) single nucleotide variant Pathogenic,risk factor rs118192162 GRCh38 Chromosome 19, 38455359: 38455359
32 RYR1 NM_000540.2(RYR1): c.97A> G (p.Lys33Glu) single nucleotide variant Pathogenic rs193922746 GRCh37 Chromosome 19, 38931436: 38931436
33 RYR1 NM_000540.2(RYR1): c.97A> G (p.Lys33Glu) single nucleotide variant Pathogenic rs193922746 GRCh38 Chromosome 19, 38440796: 38440796
34 RYR1 NM_000540.2(RYR1): c.7522C> T (p.Arg2508Cys) single nucleotide variant Pathogenic/Likely pathogenic rs118192178 GRCh37 Chromosome 19, 38991538: 38991538
35 RYR1 NM_000540.2(RYR1): c.7522C> T (p.Arg2508Cys) single nucleotide variant Pathogenic/Likely pathogenic rs118192178 GRCh38 Chromosome 19, 38500898: 38500898
36 RYR1 NM_000540.2(RYR1): c.11958C> G (p.Asp3986Glu) single nucleotide variant Pathogenic rs193922842 GRCh38 Chromosome 19, 38543821: 38543821
37 RYR1 NM_000540.2(RYR1): c.11958C> G (p.Asp3986Glu) single nucleotide variant Pathogenic rs193922842 GRCh37 Chromosome 19, 39034461: 39034461
38 RYR1 NM_000540.2(RYR1): c.14918C> T (p.Pro4973Leu) single nucleotide variant Likely pathogenic rs146876145 GRCh38 Chromosome 19, 38586140: 38586140
39 RYR1 NM_000540.2(RYR1): c.14918C> T (p.Pro4973Leu) single nucleotide variant Likely pathogenic rs146876145 GRCh37 Chromosome 19, 39076780: 39076780
40 RYR1 NM_000540.2(RYR1): c.1589G> A (p.Arg530His) single nucleotide variant Pathogenic rs111888148 GRCh38 Chromosome 19, 38455463: 38455463
41 RYR1 NM_000540.2(RYR1): c.1589G> A (p.Arg530His) single nucleotide variant Pathogenic rs111888148 GRCh37 Chromosome 19, 38946103: 38946103
42 RYR1 NM_000540.2(RYR1): c.1841G> T (p.Arg614Leu) single nucleotide variant Pathogenic rs193922772 GRCh38 Chromosome 19, 38457546: 38457546
43 RYR1 NM_000540.2(RYR1): c.1841G> T (p.Arg614Leu) single nucleotide variant Pathogenic rs193922772 GRCh37 Chromosome 19, 38948186: 38948186
44 RYR1 NM_000540.2(RYR1): c.5183C> T (p.Ser1728Phe) single nucleotide variant Pathogenic rs193922781 GRCh38 Chromosome 19, 38485838: 38485838
45 RYR1 NM_000540.2(RYR1): c.5183C> T (p.Ser1728Phe) single nucleotide variant Pathogenic rs193922781 GRCh37 Chromosome 19, 38976478: 38976478
46 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh38 Chromosome 19, 38499649: 38499651
47 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh37 Chromosome 19, 38990289: 38990291
48 RYR1 NM_000540.2(RYR1): c.7048G> A (p.Ala2350Thr) single nucleotide variant Pathogenic rs193922802 GRCh38 Chromosome 19, 38499655: 38499655
49 RYR1 NM_000540.2(RYR1): c.7048G> A (p.Ala2350Thr) single nucleotide variant Pathogenic rs193922802 GRCh37 Chromosome 19, 38990295: 38990295
50 RYR1 NM_000540.2(RYR1): c.7360C> T (p.Arg2454Cys) single nucleotide variant Pathogenic/Likely pathogenic rs193922816 GRCh38 Chromosome 19, 38500642: 38500642
Sources

Expression for Malignant Hyperthermia 1

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Search GEO for disease gene expression data for Malignant Hyperthermia 1.
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Pathways for Malignant Hyperthermia 1

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GO Terms for Malignant Hyperthermia 1

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Sources for Malignant Hyperthermia 1

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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