The Genetic Foundations of Serotonin Syndrome, Neuroleptic Malignant Syndrome, and Malignant Hyperthermia: Is There a Genetic Association Between These Disorders?

Neuroleptic malignant syndrome (NMS), serotonin syndrome (SS), and malignant hyperthermia (MH) share similar clinical characteristics. These conditions can present life-threatening situations due to exposure to different drugs. A similar genetic predisposition is suspected between these syndromes as well. This review aims to consolidate the knowledge about the genetics of these disorders and find possible correlations among them to frame the best possible approaches using different drugs without producing life-threatening complications that can be preventable. As a method, we collected data using PubMed with a Medical Subject Headings (MeSH) strategy. The inclusion criteria were as follows: full papers, studies conducted on humans, papers published in the English language, and study types that included case reports, journal articles, multicenter studies, clinical studies, observational studies, or clinical trials. Studies involving animals, articles that were without a visible abstract, study types that included clinical reviews, systematic reviews, or meta-analyses were excluded. 146 papers were reviewed, and 130 papers were removed for no possible extraction of data, duplication of the data, or the study outcome was not compatible with the objective of this review. Ultimately, a total of 17 papers were used for the discussion of this article. As a result of this review, we found no genetic association between NMS, SS, and MH development. Finally, we conclude that NMS, SS, and MH presentation are caused by different mutations which are not associated. However, because of the life-threatening clinical presentation of these conditions, genetic tests should be suggested in patients with a family history of these disorders before administering any pertinent drug that increases the risk of developing all these syndromes.