Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.
Genetic conditions can affect a patient’s response to anesthesia. Some inherited disorders change how anesthetic drugs are processed, while others affect the airway, muscles, heart, lungs, liver, or kidneys. These differences can increase complications during sedation and surgery (1). Genetic variation can influence how long certain medications remain active or how strongly a patient responds to them. Reviewing a patient’s diagnosis, medical history, family history, and previous reactions to anesthesia is important for safe anesthetic planning.
Malignant hyperthermia is a well-known inherited condition affecting anesthesia. It is most often associated with variants in the RYR1 gene, with other muscle-related genes involved less often (2). In susceptible patients, certain inhaled anesthetics and succinylcholine (a neuromuscular blocking agent) can trigger excessive calcium release within skeletal muscle cells. This causes sustained muscle activity and a rapid increase in metabolism. Early signs may include rising carbon dioxide levels, a rapid heart rate, muscle rigidity, and metabolic abnormalities. Body temperature may also rise rapidly as the reaction progresses. If untreated, malignant hyperthermia can lead to muscle breakdown, abnormal heart rhythms, kidney injury, and cardiovascular collapse. Management requires immediate discontinuation of triggering agents and prompt treatment with dantrolene (2).
Another inherited condition that can affect anesthesia is butyrylcholinesterase deficiency, also known as pseudocholinesterase deficiency. People with this disorder have reduced activity of the enzyme responsible for breaking down medications such as succinylcholine and mivacurium (3). When the enzyme does not function normally, these drugs remain active longer than expected, leading to prolonged neuromuscular paralysis after anesthesia. Affected patients may be unable to breathe independently and may require continued sedation and mechanical ventilation until muscle function returns (3). The condition is often first recognized after unexpected prolonged postoperative paralysis, although a similar reaction in a close family member can provide an important clue before surgery. Identifying the disorder in advance allows clinicians to avoid these medications or select alternative neuromuscular blocking agents.
Genetic conditions that cause muscle disorders can increase anesthesia-related risk. Duchenne and Becker muscular dystrophies are inherited disorders caused by a deficiency or abnormality of dystrophin, a protein that helps maintain the stability of muscle cells. Duchenne muscular dystrophy is generally more severe, while Becker muscular dystrophy tends to progress more slowly. Both conditions cause progressive muscle weakness and can affect the heart and respiratory muscles (4). Succinylcholine, which can trigger malignant hyperthermia in susceptible patients, poses a different danger in people with Duchenne or Becker muscular dystrophy. Because their muscle cell membranes are unusually fragile, exposure to succinylcholine can cause extensive muscle breakdown and release large amounts of potassium into the bloodstream. The resulting hyperkalemia can lead to serious cardiac arrhythmias and, in severe cases, cardiac arrest (4). Although this reaction can resemble malignant hyperthermia, it occurs through a different mechanism.
Genetic conditions can also affect patient response to anesthesia through structural abnormalities or organ-system involvement rather than a direct drug reaction. Craniofacial abnormalities can make airway management and intubation more difficult, while cardiac or respiratory disease may reduce a patient’s ability to tolerate anesthesia. Kidney and liver dysfunction may also alter how anesthetic medications are processed and eliminated (1). Careful preoperative evaluation of the genetic diagnosis, previous anesthetic experiences, family history, medications, and associated medical problems can help identify these risks before surgery. This information allows the anesthesia team to modify drug selection, monitoring, and airway management to fit the patient’s individual needs.
References
- Butler MG, Hayes BG, Hathaway MM, Begleiter ML. Specific genetic diseases at risk for sedation/anesthesia complications. Anesth Analg. 2000;91(4):837-855. doi:10.1097/00000539-200010000-00014
- Cong Z, Wan T, Wang J, et al. Epidemiological and clinical features of malignant hyperthermia: A scoping review. Clin Genet. 2024;105(3):233-242. doi:10.1111/cge.14475
- Snak de Souza CD, Ibarra Moreno CA, Riazi S, Hopkins PM. Genotype-phenotype relationships in butyrylcholinesterase deficiency: a systematic review. Br J Anaesth. 2026;137(2):450-459. doi:10.1016/j.bja.2026.03.056
- Segura LG, Lorenz JD, Weingarten TN, et al. Anesthesia and Duchenne or Becker muscular dystrophy: review of 117 anesthetic exposures. Paediatr Anaesth. 2013;23(9):855-864. doi:10.1111/pan.12248