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Malignant hyperthermia, susceptibility to, 1(MHS1)

MedGen UID:: 443948
•Concept ID:: C2930980
•: Finding

Synonyms:	Anesthesia related hyperthermia; Fulminating hyperpyrexia; Malignant hyperpyrexia; Malignant hyperthermia suceptibility 1; MHS1; Pharmacogenic myopathy; RYR1-Related Malignant Hyperthermia Susceptibility

Gene (location): Gene(s) directly associated with this condition or phenotype.	RYR1 (19q13.2)

Monarch Initiative:	MONDO:0007783
OMIM®:	145600

Disease characteristics

Excerpted from the GeneReview: Malignant Hyperthermia Susceptibility

Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high. [from GeneReviews]

Authors:
Henry Rosenberg | Nyamkhishig Sambuughin | Sheila Riazi, et. al. view full author information

Additional description

From MedlinePlus Genetics
While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease, multiminicore disease, and STAC3 disorder) are associated with malignant hyperthermia susceptibility.

Affected individuals may be at increased risk for "awake" malignant hyperthermia, in which the severe reaction occurs in response to physical activity, often while sick, rather than in reaction to exposure to a triggering drug.

People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). Malignant hyperthermia may not occur every time anesthesia is used. Many individuals who develop a severe reaction have previously been exposed to a triggering drug and not had a reaction.

Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate and body temperature (hyperthermia), abnormally fast breathing, muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Without prompt treatment and cessation of the drugs, the body's reaction can cause multiple organs to be unable to function, including the heart (cardiac arrest) and kidneys (renal failure), and it can cause a blood clotting abnormality called disseminated intravascular coagulation. These complications may be life-threatening. (In medicine, the term malignant refers to conditions that are dangerous to one's health.) https://medlineplus.gov/genetics/condition/malignant-hyperthermia

Clinical features

From HPO

Hereditary myoglobinuria

MedGen UID:: 44557
•Concept ID:: C0027080
•: Finding

Presence of myoglobin in the urine.

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Hypotension

MedGen UID:: 5715
•Concept ID:: C0020649
•: Finding

Low Blood Pressure, vascular hypotension.

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Tachycardia

MedGen UID:: 21453
•Concept ID:: C0039231
•: Finding

A rapid heartrate that exceeds the range of the normal resting heartrate for age.

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Abnormality of the coagulation cascade

MedGen UID:: 604
•Concept ID:: C0005779
•: Disease or Syndrome

An abnormality of the coagulation cascade, which is comprised of the contact activation pathway (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway) as well as cofactors and regulators.

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Rigidity

MedGen UID:: 7752
•Concept ID:: C0026837
•: Sign or Symptom

Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.

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Rhabdomyolysis

MedGen UID:: 19775
•Concept ID:: C0035410
•: Pathologic Function

Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream.

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Hyperkalemia

MedGen UID:: 5691
•Concept ID:: C0020461
•: Finding

An abnormally increased potassium concentration in the blood.

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Hyperphosphatemia

MedGen UID:: 39326
•Concept ID:: C0085681
•: Disease or Syndrome

An abnormally increased phosphate concentration in the blood.

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Elevated circulating creatine kinase concentration

MedGen UID:: 69128
•Concept ID:: C0241005
•: Finding

An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

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Mixed respiratory and metabolic acidosis

MedGen UID:: 333546
•Concept ID:: C1840372
•: Finding

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Malignant hyperthermia

MedGen UID:: 1830388
•Concept ID:: C5779784
•: Pathologic Function

Malignant hyperthermia is characterized by a rapid increase in temperature to 39-42 degrees C. Malignant hyperthermia may occur in response to either inhalational anesthetics such as halothane, to muscle relaxants such as succinylcholine, or to exercise.

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