HyperCKemia and rhabdomyolysis in the neuroleptic malignant and serotonin syndromes: A literature review

N. Kruijt*, L. R. van den Bersselaar, J. Wijma, W. Verbeeck, M. J.H. Coenen, J. Neville, M. Snoeck, E. J. Kamsteeg, H. Jungbluth, C. Kramers, N. C. Voermans

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)


Neuroleptic malignant syndrome and serotonin syndrome are two syndromes whose molecular bases remain poorly understood. The phenotypes of both syndromes overlap with other syndromes that have a clear genetic background, in particular RYR1-related malignant hyperthermia. Through a literature review, performed according to the PRISMA guidelines, we aimed to report the clinical features of both syndromes, and the results of genetic testing performed. 10 case series and 99 case reports were included, comprising 134 patients. A male predominance of 58% was found. The median age was 35 (range 4–84) years. Eight patients experienced recurrent episodes of rhabdomyolysis. Genetic analysis was performed in eleven patients (8%), revealing four RYR1 variants, three likely benign (p.Asp849Asn, p.Arg4645Gln, p.Arg4645Gln) and one variant of uncertain significance (p.Ala612Thr). This review underlines that a subset of patients with neuroleptic malignant syndrome and serotonin syndrome develop recurrent episodes of rhabdomyolysis. This recurrent pattern suggests a possible underlying (genetic) susceptibility. However, the genetic background of neuroleptic malignant syndrome and serotonin syndrome has only been investigated to a very limited degree so far. The increasing availability of next generation sequencing offers an opportunity to identify potentially associated genetic backgrounds, especially in patients with recurrent episodes or a positive family history.

Original languageEnglish
Pages (from-to)949-958
Number of pages10
JournalNeuromuscular Disorders
Issue number12
Publication statusPublished - Dec 2020


  • Neuroleptic malignant syndrome
  • Rhabdomyolysis
  • RYR1
  • Serotonin syndrome


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