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.

中文翻译：

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抗精神病药恶性和血清素综合征中的高CK血症和横纹肌溶解症：文献综述

抗精神病药恶性综合征和血清素综合征是两种分子基础仍然知之甚少的综合征。这两种综合征的表型与具有明确遗传背景的其他综合征重叠，特别是与 RYR1 相关的恶性高热。通过根据 PRISMA 指南进行的文献综述，我们旨在报告这两种综合征的临床特征，以及所进行的基因检测结果。包括10个病例系列和99个病例报告，包括134名患者。发现男性占优势的比例为 58%。中位年龄为 35（范围 4-84）岁。八名患者经历了反复发作的横纹肌溶解症。对 11 名患者 (8%) 进行了遗传分析，揭示了四种 RYR1 变体，其中三种可能是良性的 (p.Asp849Asn、p.Arg4645Gln、p. 12)。Arg4645Gln）和一种意义不确定的变体（p.Ala612Thr）。本综述强调，一部分患有抗精神病药恶性综合征和 5-羟色胺综合征的患者会反复发作横纹肌溶解症。这种反复出现的模式表明可能存在潜在的（遗传）易感性。然而，迄今为止，抗精神病药恶性综合征和血清素综合征的遗传背景仅在非常有限的程度上得到了研究。下一代测序的日益普及提供了识别潜在相关遗传背景的机会，特别是在复发性发作或阳性家族史的患者中。这种反复出现的模式表明可能存在潜在的（遗传）易感性。然而，迄今为止，抗精神病药恶性综合征和血清素综合征的遗传背景仅被研究到非常有限的程度。下一代测序的日益普及提供了识别潜在相关遗传背景的机会，特别是在复发性发作或阳性家族史的患者中。这种反复出现的模式表明可能存在潜在的（遗传）易感性。然而，迄今为止，抗精神病药恶性综合征和血清素综合征的遗传背景仅被研究到非常有限的程度。下一代测序的日益普及提供了识别潜在相关遗传背景的机会，特别是在复发性发作或阳性家族史的患者中。