Peer-reviewed veterinary case report
Fatal malignant hyperthermia in two pet dogs linked to new gene
By Perez Jimenez, Tania E et al.·Published in Veterinary anaesthesia and analgesia·2025·Department of Veterinary Clinical Sciences, United States·View original on PubMed →
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Original publication title: Novel ryanodine receptor 1 (RYR1) missense gene variants in two pet dogs with fatal malignant hyperthermia identified by next-generation sequencing.
- Species:
- dog
Plain-English summary
A 7-year-old male Pit Bull mix and a 12-month-old male Golden Retriever both experienced severe reactions during anesthesia, showing symptoms like rapid breathing, fast heart rate, high fever, and muscle stiffness. Unfortunately, despite efforts to cool them down and other treatments, both dogs suffered cardiac arrest and died shortly after these symptoms appeared. Genetic testing revealed that both dogs had specific gene variants linked to a condition called malignant hyperthermia, which can cause dangerous reactions to certain anesthetics. This case highlights the importance of genetic testing in diagnosing such conditions in dogs.
People also search for: dog anesthesia reaction · malignant hyperthermia in dogs · Pit Bull anesthesia risks · Golden Retriever anesthesia complications
Abstract
OBJECTIVE: Evaluate a precision medicine approach to confirm a tentative diagnosis of fatal malignant hyperthermia (MH) in isoflurane-anesthetized pet dogs by identifying novel risk variants in known MH susceptibility genes. STUDY DESIGN: Retrospective case series. ANIMALS: A male Pit Bull mix aged 7 years (case #1), a male Golden Retriever aged 12 months (case #2) and the dam and sire of case #2. METHODS: Available case histories and medical records were reviewed. Missense variants in MH susceptibility genes RYR-1, CACNA1S and STAC3 (case #2 only) were identified by next-generation sequencing of DNA from each case and the parents of case #2 with confirmation by Sanger sequencing. The pathogenicity of variants was evaluated by multiple in silico approaches. RESULTS: Both cases demonstrated clinical signs during isoflurane anesthesia consistent with volatile anesthetic-induced MH, including tachypnea, tachycardia, severe hyperthermia and muscle rigidity. Despite whole body cooling and other treatments, both dogs died after cardiac arrest within 15 minutes of detecting hyperthermia. Gene sequencing identified novel missense RYR-1 variants in case #1 (p.Gly2375Arg) and case #2 (p.Pro152Leu). Both variants were likely pathogenic based on multiple criteria, including gene location, amino acid alteration and population allele frequency. The case #1 variant was identical to a known human diagnostic MH variant (p.Gly2375Arg). Neither parent of case #2 had the case #2 variant, indicating this variant was not inherited, but arose de novo in a germ cell of either parent or early in embryogenesis. Whole genome sequence analysis confirmed parentage. Two missense variants were identified in CACNA1S. Both variants were considered nonpathogenic. No variants were identified in STAC3. CONCLUSIONS AND CLINICAL RELEVANCE: Like humans, MH susceptibility in dogs is associated with different rare variants located in pathogenic hotspots in the RYR-1 gene. Next-generation sequencing is a useful tool to assist in the definitive diagnosis of MH in dogs.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/39516111/