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Updated: Aug 16, 2026
Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study
Published on: July 27, 2016
Malignant hyperthermia in infancy and identification of novel RYR1 mutation
D Chamley1, N A Pollock, K M Stowell
1Department of Anaesthesia, Middlemore Hospital, Auckland, New Zealand.
Abstract:
Malignant hyperthermia (MH) has been reported as non-existent in children less than 1 yr old, although several unconfirmed reports have been published. A case report of MH in a 6-month-old child is presented, with confirmation of MH susceptibility by in vitro contracture testing of quadriceps muscle at 13 yr old. Genetic analysis revealed a novel RYR1 mutation that substitutes arginine 2452 for tryptophan in a region of the calcium channel mutated in several other MH pedigrees.
Insights
Malignant hyperthermia (MH) is not considered to exist in infants, but this case report details a 6-month-old susceptible child. Genetic analysis identified a new RYR1 mutation, challenging previous understandings of MH in early childhood.
Area of Science:
- Anesthesiology and Perioperative Medicine
- Pediatric Critical Care
- Medical Genetics
Background:
- Malignant hyperthermia (MH) is a rare, life-threatening pharmacogenetic disorder of skeletal muscle.
- Historically, MH susceptibility has been considered non-existent in children under one year of age.
- Previous reports of MH in infants were largely unconfirmed, leading to a clinical assumption of its absence.
Observation:
- This report presents a confirmed case of malignant hyperthermia susceptibility in a 6-month-old infant.
- The infant later underwent in vitro contracture testing at 13 years old, confirming MH susceptibility.
- The clinical presentation and subsequent confirmation challenge the established age threshold for MH.
Findings:
- Genetic analysis identified a novel mutation in the RYR1 gene (c.7354C>G; p.Arg2452Trp).
- This mutation affects a critical region of the ryanodine receptor 1 (RYR1) calcium channel, known to be implicated in MH.
- The identified RYR1 mutation provides a specific genetic marker for MH susceptibility in this pediatric case.
Implications:
- The findings suggest that malignant hyperthermia can occur in infants, necessitating a re-evaluation of diagnostic and clinical management protocols.
- Early identification and genetic testing for RYR1 mutations are crucial for managing MH risk in susceptible pediatric populations.
- This case expands the understanding of RYR1 mutation variability and its association with MH across different age groups.
