Objective: To describe the clinical features, genetic characteristics, and diagnosis of Marsili syndrome, an extremely rare disease which should be differentiated from other fever disorders. Methods: The clinical data and diagnostic process of a case with Marsili syndrome, hospitalized in the Department of Respiratory and Critical Care Medicine, the Eighth Medical Center of Chinese PLA General Hospital in February 2021, were summarized. The exon regions of 20, 000 genes of peripheral blood were detected in the patient and her parents. Using key words of"Marsili syndrome"and"ZFHX2 gene mutation", the related literatures were searched in Wanfang and PubMed databases from January, 2000 to November, 2021. In addition, the literatures of congenital insensitivity to pain and anhidrosis were retrieved in Wanfang domestic database from the same period. Results: A 23-year-old female patient had suffered from recurrent fever for more than two years, accompanied by anhidrosis, insensitive to pain and weakened corneal reflex. The effect of non-steroidal anti-inflammatory drugs for fever was minimal. The ZFHX2 gene mutation was positive in the patient and her mother, while NTRK1 gene mutation specific to congenital insensitivity to pain with anhidrosis (CIPA) was negative. The ZFHX2 gene mutation was negative in her father. A total of 2 literatures of Marsili syndrome were retrieved and a total of 6 cases of Marsili syndrome in one family were reported worldwide up to now. These patients had a group of similar symptoms including fever, little or no sweating, and insensitivity to pain caused by skin burn and bone fracture. However, there was no abnormality in headache and visceral pain, and female patients' childbirth pain as well as tactile sensation in these cases. The corneal reflex was decreased or negative. They had less sensitivity to stimulus of capsaicin. The ZFHX2 gene mutation was positive, but NTRK1 gene was not detected in all patients. A total of 4 literatures were retrieved and a total of 34 cases of CIPA were reported in China. Though Marsili syndrome and CIPA exhibited a number of similar clinical manifestations, they were distinct diseases and had obviously different outcome. Conclusions: Marsili syndrome is an autosomal dominant genetic disease. It is extremely rare worldwide. In clinical practice, when a patient presents with unexplained recurrent fever and poor effect of non-steroidal anti-inflammatory drugs, especially with the symptoms of no sweating and insensitivity to pain, the possibility of Marsili syndrome should be considered and the ZFHX2 gene should be determined. Marsili syndrome appears to be a benign disease with a good prognosis. A definitive diagnosis can avoid ineffective treatment and its adverse effects. To our knowledge, there is currently no effective genetic therapy for this disease.
目的： 探讨罕见疾病Marsili综合征的临床特征、遗传规律、诊断方法及与其他引起发热症状疾病的鉴别诊断。 方法： 总结2021年2月解放军总医院第八医学中心呼吸与危重病医学科确诊的1例Marsili综合征临床资料，对患者及其父母外周血2万个基因的外显子区进行检测。以“Marsili综合征”，“ZFHX2基因突变”为关键词，检索自2000年1月至2021年11月的万方数据库和PubMed数据库相关文献并进行复习。此外，又以“先天疼痛不敏感”及“无汗”为关键词检索国内万方数据库并复习有关文献。 结果： 患者女性，23岁，临床表现为反复发热2年余，非甾体类抗炎药退热效果差，伴无汗及对疼痛不敏感，眼角膜反射减弱。患者及其母亲ZFHX2基因突变阳性，先天性无痛无汗症特有的NTRK1基因突变阴性，其父亲ZFHX2基因突变阴性。文献检索发现有关Marsili综合征英文文献2篇，世界范围内仅报告1个家庭中6例Marsili综合征病例，国内尚未见报道。本病临床表现为感觉疼痛、温度及出汗能力减弱或消失；对皮肤烧灼伤和骨折引起的疼痛不敏感，但对头痛、内脏痛、女性患者分娩痛及触觉无异常；角膜反射消失或迟钝；对辣椒素刺激敏感性下降。所有患者ZFHX2基因突变阳性，但未测定NTRK1基因。此外，国内有关先天性无痛无汗症文献4篇，共报告病例34例。Marsili综合征和先天性无痛无汗症虽有一些相同的临床表现，但两者是不同的疾病，且预后完全不同。 结论： Marsili综合征是一种常染色体显性遗传病，国内外极其罕见。临床遇到不明原因反复发热，使用非甾体类抗炎药效果差，尤其是合并无汗、对疼痛不敏感等临床表现应想到本病的可能性，并进行ZFHX2基因检测。本病为良性疾病，预后良好，尽早明确诊断可避免无效治疗及其不良反应。针对本病目前尚无有效的基因治疗方法。.