[Malignant Hyperthermia - Update on Pathophysiology, Diagnostics and Treatment].

Area of Science:

• Anesthesiology
• Genetics
• Pharmacology

Background:

• Malignant hyperthermia (MH) is a rare, life-threatening pharmacogenetic disorder of skeletal muscle.
• It is triggered by volatile anesthetics and succinylcholine, leading to hypermetabolism.
• Pathogenic variants in the RYR1 gene are identified in over 50% of MH cases, causing uncontrolled calcium release.

Purpose of the Study:

• To review the pathophysiology, clinical presentation, and diagnostic approaches for Malignant hyperthermia.
• To highlight the role of genetic testing and in-vitro contracture testing in MH diagnosis.
• To provide guidance on investigating MH predisposition in at-risk individuals.

Main Methods:

• Review of current literature and European guidelines on Malignant hyperthermia diagnosis and management.
• Discussion of genetic testing strategies, including RYR1 gene sequencing.
• Emphasis on the diagnostic utility of in-vitro contracture testing (IVCT) when genetic screening is inconclusive.

Main Results:

• The genetic prevalence of MH susceptibility is estimated at 1:2750, with incomplete penetrance.
• Characteristic symptoms of MH crisis include hypercarbia, tachycardia, acidosis, hyperthermia, rigidity, and rhabdomyolysis.
• DNA screening is a primary diagnostic tool, but IVCT remains the gold standard for safely excluding MH predisposition when genetic variants are not found.

Conclusions:

• Early diagnosis and prompt treatment with dantrolene are crucial for managing MH crises.
• Genetic screening is a valuable first step in diagnosing MH predisposition.
• In vitro contracture testing is essential for definitive exclusion of MH susceptibility when genetic tests are negative.