中国实用儿科杂志

中国实用儿科杂志 ›› 2022, Vol. 37 ›› Issue (10): 771-775.DOI: 10.19538/j.ek2022100613

• 论著 • 上一篇    下一篇

TH基因相关多巴反应性肌张力不全临床表型和基因变异特点10例分析#br#
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  1. 1.北京大学第一医院儿科，北京  100034，2.秦皇岛市妇幼保健院儿科，河北  秦皇岛  066000
  • 出版日期:2022-10-06 发布日期:2022-11-11
  • 通讯作者: 杨莹，电子信箱：yang_ying616@126.com

Clinical phenotypes and gene mutation features of TH gene-related dopa-responsive dystonia

  1. *Department of Pediatrics，Peking University First Hospital，Beijing  100034，China
  • Online:2022-10-06 Published:2022-11-11

摘要： 目的　总结TH基因相关的多巴反应性肌张力不全（DRD）临床表型及基因变异特点。方法　回顾性收集2014年1月至2021年7月在北京大学第一医院儿科门诊就诊的TH基因相关DRD患儿资料，对其临床表现和基因检测结果进行分析。结果　共收集10例TH基因复合杂合变异相关的DRD患儿资料，含13种不同变异，其中9种变异国际已报道（p.Arg233His、p.Arg169Stop、p.Arg318X、p.Arg202His、p.Arg153*、p.Thr404Met和p.Gly247Ser、p.Gly284Ser、p.Gly216Ser），4种变异是国际上尚未报道的新变异（c.738-2A>G、Exon3-8（del）、p.Thr399Thr和c.580+1G>C）。10例起病年龄为3～10月龄（中位年龄为4月龄）。以发作性双眼斜视起病1例，以姿势异常起病1例，以发作性肢体僵硬起病1例，以运动发育落后起病7例。10例患儿均有运动发育落后，7例有语言发育落后，5例有发作性双眼斜视，3例有发作性肢体僵硬，2例有足尖行走，2例有伸舌困难，2例有流涎，2例有非癫痫性肌阵挛，1例有足外翻，1例有发作性双侧腕关节屈曲。10例均给予口服多巴丝肼治疗，发作性双眼斜视、肢体僵硬、伸舌困难、流涎、非癫痫性肌阵挛及发作性双侧腕关节屈曲症状治疗后消失；7例运动发育恢复正常，3例较前进步；2例语言发育恢复正常，5例较前进步；1例足尖行走姿势消失，1例较前改善；1例足外翻较前改善。结论　TH基因变异相关DRD的临床特点为婴儿期起病，以运动和语言发育落后、发作性双眼斜视和肢体僵硬为主要表现。口服多巴丝肼可明显改善症状，但少数患儿会遗留语言、运动功能障碍及足外翻。

关键词: TH基因, 肌张力不全, 发育落后, 治疗, 预后

Abstract: Objective　To summarize the phenotypes and genotypes of dopa-responsive dystonia（DRD）associated with TH gene. Methods　The clinical data of children with TH gene-related DRD from January 2014 to July 2021 were collected retrospectively，and the clinical manifestations and gene detection results were analyzed. Results　A total of 10 DRD children with compound heterozygous variants of TH gene were collected.There were 13 different variants，9 of which were reported previously（p.Arg233His，p.Arg169Stop，p.Arg318X，p.Arg202His，p.Arg153*，p.Thr404Met，p.Gly247Ser，p.Gly284Ser and p.Gly216Ser），4 were novel variants，including c.738-2A>G，exon 3-8（del），p.Thr399Thr and c.580+1G>C. The onset age of 10 cases was 3 months to 10 months（median age was 4 months）. The onset symptom was paroxysmal binocular strabismus in one patient，abnormal posture in one patient，paroxysmal limb stiffness in one patient，and motor developmental delay in 7 patients. All 10 patients had motor developmental delay，7 patients had delayed language development，5 patients had paroxysmal binocular strabismus，3 patients had paroxysmal limb stiffness，2 patients had toe walking，2 patients had difficulty in stretching tongue，2 patients had salivation，2 patients had myoclonus，and one patient had valgus，one patient had paroxysmal wrist incurve.All 10 patients were treated with levodopa and benserazide hydrochloride. After the treatment，the symptoms of paroxysmal binocular strabismus，limb stiffness，difficulty in stretching tongue，salivation，non-epileptic myoclonus and paroxysmal wrist incurve in the patients disappeared.Motor development became normal in 7 patients and improved in 3 patients. Language development became normal in 2 patients and improved in 5 patients.Toe walking was disappeared in one patient，the other patient was improved.Valgus improved in one patient. Conclusion　The clinical features of TH gene-related DRD include the symptom onset in infancy，and the main manifestations are motor and language developmental delay，paroxysmal binocular strabismus and limb stiffness.Oral administration of Tevodopa & benserazide is effective.Some patients still have language or motor dysfunction and valgus.

Key words: TH gene, dystonia, developmental delay, treatment, prognosis