Skip to main content

Calcium Voltage-Gated Channel subunit alpha 1S (CACNA1S)

CACNA1S is part of the calcium channel receptor that instructs the nerve to the muscle to cause a muscle contraction.  Variations in the CACNA1S gene cause the muscles to be very sensitive to certain medications. Two of these variations are associated with a serious side effect called malignant hyperthermia that may occur after exposure to certain medicines. Clinical features of malignant hyperthermia include prolonged muscle contraction which can lead to a fast or irregular heartbeat, fever, and possibly severe muscle breakdown if untreated. Genetic testing of the CACNA1S and the related RYR1 gene can assist in identifying patients at high risk of developing malignant hyperthermia (MH).

Priority CACNA1S phenotype

  • Increased risk of developing malignant hyperthermia – Patients who have inherited a known malignant hyperthermia-causative variant (also called pathogenic variant) in the CACNA1S gene are susceptible to developing malignant hyperthermia when exposed to the depolarizing neuromuscular blocker succinylcholine and/or the volatile inhaled anesthetics (enflurane, methoxyflurane, desflurane, halothane, isoflurane, sevoflurane). Less than 0.07% of people have a known malignant hyperthermia-causative variant in RYR1 or CACNA1S.
    • Drugs we recommend to avoid due to a high risk of developing malignant hyperthermia:
      • Halogenated volatile anesthetics: Enflurane, methoxyflurane, desflurane, halothane, isoflurane, sevoflurane. Use alternative anesthetic medications such as propofol supplemented by benzodiazepines, opioids, nitrous oxide, and regional anesthetic techniques if needed. Amide and ester local anesthetic agents can be used in these patients.
      • Depolarizing neuromuscular blocker: Succinylcholine. Use non-depolarizing neuromuscular blockers such as mivacurium, atracurium, rocuronium, pancuronium, cisatracurium, and vecuronium.

Routine CACNA1S phenotype

  • Normal risk of developing malignant hyperthermia– In patients with this genotype, the risk of developing malignant hyperthermia after exposure to succinylcholine or halogenated volatile anesthetics is the same as the general population. It should be noted that these medicines might still cause malignant hyperthermia even for people in this category. Family history, clinical findings, and other laboratory tests should be considered in making clinical decisions regarding anesthetic agent selection.

More information for patients

  • If you have questions or concerns about pharmacogenetic testing done at St. Jude,  you can email the pharmacogenetics team at pharmacogenomics@stjude.org, or call one of the Pharmaceutical Sciences Research Nurses at 901-595-2482. If you are calling from outside of the Memphis area, dial toll free 1-866-2ST-JUDE (1-866-278-5833), then dial extension 2482.

More information for healthcare professionals

 
 

Legal Disclaimer: This page is intended to provide implementers with guidance on establishing a clinical pharmacogenetic program at their institution. Information contained on this page is for information and educational purposes only. Although reasonable efforts have been made to ensure that the information provided on this page is current, complete and, where appropriate, based on scientific evidence, St. Jude Children's Research Hospital makes no assurances as to whether the provided information will at all times be current or complete. St. Jude Children's Research Hospital, in offering this document, is not providing medical advice or offering a consultative opinion, and is not establishing a treatment relationship with any given individual. You, therefore, should not substitute information contained herein for your own professional judgment, nor should you rely on information provided herein in rendering a diagnosis or choosing a course of treatment for a particular individual.