DGM (Dutch-German Mennonite)

Inheritance: autosomal dominant
Genes: RYR1

MHS1
MH
Hyperthermia of anesthesia
King Syndrome

Myopathy
Hyperpyrexia
Post-anesthesia hyperthermia
Rhabdomyolysis

Malignant Hyperthermia, Susceptibility to

Clinical Characteristics

General description (for patients):

During and after general anesthesia, some patients develop severe muscle damage and extremely high body temperatures.  It may even result in death.  Some individuals who are susceptible to such post-anesthesia complications may have similar muscle damage following severe exercise in hot weather, certain drugs including alcohol, and viral infections.

Medical description: 

Susceptibility to hyperthermia is widely known as a complication of general anesthesia with certain agents, particularly volatile inhalation anesthetics and succinylcholine.  It can be detected pre-operatively with the in vitro caffeine/halothane contracture test (CHCT) in fresh muscle biopsies but this test lacks 100% specificity.  Since the inheritance pattern is usually autosomal dominant, a good family history is vital.  Myopathy and rhabdomyolysis, sometimes severe, are common as evidenced by elevated creatinine kinase and by myoglobinuria.  Susceptible individuals may exhibit the same symptoms and signs after ingesting certain drugs including alcohol, during viral illness, and after intense exercise in hot weather.

Genetics:

This may be a heterogeneous category of disease.  At least eight different genes on different chromosomes have been associated with susceptibility to malignant hyperthermia but perhaps 50% have a mutation of the skeletal muscle ryanodine receptor gene RYR1 located on chromosome 19 (19q13.1). Familial cases show an autosomal dominant pattern of inheritance.  An 1840C>T substitution at 19q13.1 has been identified in a large Manitoba Mennonite kindred.

Treatment:

Dantrolene sodium can be given intravenously for malignant hyperthermia, and the oral form has been approved for prophylactic use.  Ice water immersion for dangerous levels of hyperpyrexia is used as well.
PROGNOSIS:  Prompt recognition and treatment of this complication can be life-saving.  Susceptible individuals may be treated prophylactically with Dantrium.

Ancillary treatments and support:

Pre-operative ascertainment is important but those who live through an episode may require various levels of care commensurate with the muscle and neurological damage.

Specialists and specialty centers:

Anesthesiologist, Internist.

References:

Serfas, K.D., Bose, D., Patel, L, Wrogemann, K., Phillips, M.S., MacLennan, D.H., and Greenberg, C.R.:  Comparison of the segregation of the RYR1 C1840T mutation with segregation of the caffeine/halothane contracture test results for malignant hyperthermia susceptibility in a large Manitoba Mennonite family.  Anesth. 84: 322-329, 1996. PubMed ID: 8602662

Monnier, N., Kozak-Ribbens, G., Krivosic-Horber, R., Nivoche, Y., Qi, D., Kraev, N., Loke, J., Sharma, P., Tegazzin, V., Figarella-Branger, D., Romero, N., Mezin, P., Bendahan, D., Payen, J.-F., Depret, T., Maclennan, D.H., and Lunardi, J.: Correlations between genotype and pharmacological histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.  Hum. Mutat. 26: 413-425, 2005.  PubMed ID: 16163667

Resources:

Malignant Hyperthermia Association of the United States

Associated Graphics