OMIA 000621-9615 : Malignant hyperthermia in Canis lupus familiaris |
Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT
History: Malignant hyperthermia was first reported in humans in 1960 and in dogs in 1973 (Short and Paddleford, 1973). Mapping: CFA1 Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the known molecular cause of the same disorder in pigs and humans, and reinforced by showing the candidate gene to be very tightly linked to MHS in dogs), Roberts et al. (2001) identified the causative mutation as a T to C substitution that changes an amino acid codon from valine to alanine (V547A) in a highly conserved region of the canine RYR1 gene. Clinical features: Dogs with malignant hyperthermia present as an outwardly healthy dog, but develop hypercapnea, tachycardia, and hyperthermia during general anesthesia. Signs can progress to cardiac dysrhythmia, rhabdomyolysis, renal failure, and death if the anesthetic is not discontinued. Common triggers of clinical signs include volatile inhalants (halothane, isoflurane, and sevoflurane) and depolarizing muscle relaxants such as succinylcholine (Roberts et al., 2001, Brunson et al., 2004).Treatment involves cessation of the causative anesthetic, supportive care, cooling, and dantrolene administration. Unlike affected humans or pigs (Nelson et al., 2002), affected dogs develop signs primarily in response to chemical triggers and exhibit less severe metabolic acidosis and muscle rigidity during a clinical episode (Roberts et al., 2001). Alternative anesthetic protocols for affected dogs can include nitrous oxide, benzodiazepines, phenothiazines, barbiturates, etomidate, propofol, dissociative agents, opioids, nondepolarizing neuromuscular blockers, or a combination of intravenous and local or regional anesthesia. Sufficient premedication is important, since stress can be a contributing factor to development of clinical signs (Brunson et al., 2004).
Pathology: The ryanodine receptor is part of the calcium-releasing channel in skeletal muscle. In affected dogs, chemical triggers interact directly with the ryanodine receptor to increase and prolong sarcoplasmic calcium release. This increases muscle contraction and muscle metabolism, resulting in hyperthermia (Brunson et al., 2004). Dantrolene is a muscle relaxant that blocks calcium release inside myocytes (Brunson et al., 2004). Prevalence: Although prevalence is thought to be low, it is difficult to estimate because affected dogs appear normal unless they are exposed to a trigger, and some may die before diagnosis is achieved. Control: Relatives of affected dogs should be tested. Breeding of affected dogs is discouraged. Because dogs with this mutation are often not identified before undergoing anesthesia, it is recommended that dantrolene be stocked in the surgical suite. Genetic testing: There is a test for this mutation in dogs (Roberts et al., 2001). Breeds: Collie, Doberman Pinscher, English Springer Spaniel, German Shepherd Dog, Greyhound, Labrador Retriever, Pointer, Saint Bernard. Associated gene:Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
---|---|---|---|---|---|---|
RYR1 | ryanodine receptor 1 (skeletal) | Canis lupus familiaris | 1 | NC_051805.1 (115181223..115063307) | RYR1 | Homologene, Ensembl, NCBI gene |
Variants
By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Collie Doberman Pinscher German Shepherd Dog Labrador Retriever | Malignant hyperthermia | RYR1 | missense | 1 | c.1640T>C | p.V547A | "The nucleotide sequences of canine regions I and II have been submitted to GenBank (accession No. A302128 and AF302129, respectively)" (Roberts et al., 2001) | 2001 | 11575546 |
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 | Thrift, E., Wimpole, J.A., Child, G., Brown, N., Gandolfi, B., Malik, R. : | |
Exercise-induced hyperthermia syndrome (canine stress syndrome) in four related male English springer spaniels. Vet Med (Auckl) 8:59-68, 2017. Pubmed reference: 30050857. DOI: 10.2147/VMRR.S123836. | ||
2012 | Adami, C., Axiak, S., Raith, K., Spadavecchia, C. : | |
Unusual perianesthetic malignant hyperthermia in a dog. J Am Vet Med Assoc 240:450-3, 2012. Pubmed reference: 22309018. DOI: 10.2460/javma.240.4.450. | ||
2004 | Brunson, DB., Hogan, KJ. : | |
Malignant hyperthermia: a syndrome not a disease. Vet Clin North Am Small Anim Pract 34:1419-33, 2004. Pubmed reference: 15474681. DOI: 10.1016/j.cvsm.2004.05.010. | ||
2002 | Nelson, T.E. : | |
Malignant hyperthermia: a pharmacogenetic disease of Ca++ regulating proteins. Curr Mol Med 2:347-69, 2002. Pubmed reference: 12108947. | ||
2001 | Roberts, M.C., Mickelson, J.R., Patterson, E.E., Nelson, T.E., Armstrong, P.J., Brunson, D.B., Hogan, K. : | |
Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1) Anesthesiology 95:716-725, 2001. Pubmed reference: 11575546. | ||
1998 | Xu, L., Eu, J.P., Meissner, G., Stamler, J.S. : | |
Activation of the cardiac calcium release channel (ryanodine receptor) by poly-s-nitrosylation Science 279:234-237, 1998. Pubmed reference: 9422697. | ||
1997 | Duncan, K.L., Hare, W.R., Buck, W.B. : | |
Malignant hyperthermia-like reaction secondary to ingestion of hops in five dogs Journal of the American Veterinary Medical Association 210:51 ff., 1997. | ||
Sudo, R.T., Nelson, T.E. : | ||
Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle Journal of Pharmacology & Experimental Therapeutics 282:1331-1336, 1997. | ||
1992 | Cosgrove, S.B., Eisele, P.H., Martucci, R.W., Gronert, G.A. : | |
Evaluation of Greyhound Susceptibility to Malignant Hyperthermia Using Halothane-Succinylcholine Anesthesia and Caffeine-Halothane Muscle Contractures Laboratory Animal Science 42:482-485, 1992. Pubmed reference: 1460848. | ||
1991 | Nelson, T.E. : | |
Malignant hyperthermia in dogs. J Am Vet Med Assoc 198:989-94, 1991. Pubmed reference: 2032926. | ||
1990 | Obrien, P.J., Pook, H.A., Klip, A., Britt, B.A., Kalow, B.I., Mclaughlin, R.N., Scott, E., Elliott, M.E. : | |
Canine Stress Syndrome Malignant Hyperthermia Susceptibility - Calcium-Homeostasis Defect in Muscle and Lymphocytes Research in Veterinary Science 48:124-128, 1990. Pubmed reference: 2300706. | ||
1987 | O'Brien, P.J., Fletcher, T.F., Metz, A.L., Kurtz, H.J., Reed, B.K., Rempel, W.E., Clark, E.G., Louis, C.F. : | |
Malignant hyperthermia susceptibility: cardiac histomorphometry of dogs and young and market-weight swine. Can J Vet Res 51:50-5, 1987. Pubmed reference: 3567752. | ||
O'brien, P.J. : | ||
Malignant hyperthermia in dogs. Can Vet J 28:302-3, 1987. Pubmed reference: 17422791. | ||
Rand, J.S., O'Brien, P.J. : | ||
Exercise-induced malignant hyperthermia in an English springer spaniel. J Am Vet Med Assoc 190:1013-4, 1987. Pubmed reference: 3570952. | ||
1986 | Cribb, P.H., Olfert, E.A., Reynolds, F.B. : | |
Erythrocyte osmotic fragility testing and the prediction of canine malignant hyperthermia susceptibility. Can Vet J 27:517-22, 1986. Pubmed reference: 17422730. | ||
1985 | O'Brien, P.J., Rand, J.S. : | |
Canine stress syndrome. J Am Vet Med Assoc 186:432-3, 1985. Pubmed reference: 3972704. | ||
1984 | Kirmayer, A.H., Klide, A.M., Purvance, J.E. : | |
Malignant hyperthermia in a dog: case report and review of the syndrome. J Am Vet Med Assoc 185:978-82, 1984. Pubmed reference: 6511640. | ||
O'Brien, P.J., Forsyth, G.W., Olexson, D.W., Thatte, H.S., Addis, P.B. : | ||
Canine malignant hyperthermia susceptibility: erythrocytic defects--osmotic fragility, glucose-6-phosphate dehydrogenase deficiency and abnormal Ca2+ homeostasis. Can J Comp Med 48:381-9, 1984. Pubmed reference: 6150753. | ||
1983 | Leary, S.L., Anderson, L.C., Manning, P.J., Bache, R.J., Zweber, B.A. : | |
Recurrent malignant hyperthermia in a Greyhound. J Am Vet Med Assoc 182:521-2, 1983. Pubmed reference: 6833093. | ||
O'brien, P.J., Cribb, P.H., White, R.J., Olfert, E.D., Steiss, J.E. : | ||
Canine malignant hyperthermia: diagnosis of susceptibility in a breeding colony. Can Vet J 24:172-7, 1983. Pubmed reference: 17422267. | ||
1978 | Bagshaw, R.J., Cox, R.H., Knight, D.H., Detweiler, D.K. : | |
Malignant hyperthermia in a Greyhound. J Am Vet Med Assoc 172:61-2, 1978. Pubmed reference: 624662. | ||
Cohen, C.A. : | ||
Malignant hyperthermia in a greyhound. J Am Vet Med Assoc 172:1254, 1256, 1978. Pubmed reference: 659305. | ||
1973 | Short, C.E., Paddleford, R.R. : | |
Letter: Malignant hyperthermia in the dog. Anesthesiology 39:462-3, 1973. Pubmed reference: 4758363. |
Edit History
- Created by Frank Nicholas on 12 Sep 2005
- Changed by Martha MaloneyHuss on 10 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 18 Sep 2012
- Changed by Frank Nicholas on 20 Oct 2020