幼儿多巴胺反应性肌张力障碍3例临床和遗传特点分析

摘要

目的 探讨幼儿多巴胺反应性肌张力障碍 (DRD) 的临床、遗传特点, 以及治疗和预后.方法 回顾分析2014年1月至2017年8月神经内科门诊收治的3例幼儿DRD的临床资料.结果 男性患儿2例, 分别为1岁8个月、2岁, 4岁女性患儿1例, 出生或1岁后发病, 均表现为肌张力低下.遗传学检测, 例1 TH基因突变, c.G943A (p.G315S) 来自于母亲 (PMID20056467) , c.G 739 A (p.G 247 S) 来自于父亲 (PMID 18554280, 24753243) ;例2 GCH-1基因杂合突变, c. 454-2 A＞G来自于父亲 (PMID 10732814) ;例3 TH1基因突变, c.580+2T>C来自于母亲 (首次报道) , c.698G>A (p.R233H) 来自于父亲 (PMID9703425) .其中例1母亲已再次怀孕, 产前检查发现胎儿仅携带来自于母亲的杂合突变位点c.G 943 A (p.G 315 S) .3例患儿确诊后予小剂量多巴丝肼治疗, 逐渐加量至获得最佳疗效, 随访6个月, 例1、例2基本恢复正常, 例3肌张力障碍明显改善, 但遗留足部畸形.结论 DRD于婴幼儿期起病, 早期症状不典型, 遗传学检测可明确诊断, 具有先证者家庭应予产前检查.%Objective To explore the clinical and genetic characteristics, treatment. and prognosis of dopamine responsive dystonia (DRD) in children. Method The clinical data of DRD in 3 children admitted to neurology clinic from January 2014 to August 2017 were retrospectively analyzed. Results Two male children, 20-month-old and 2-year-old respectively, and one 4-year-old female child suffered from hypotonia after birth or one year after birth. Genetic testing found that case 1 had heterozygous mutations in tyrosine hydroxylase (TH) gene, C. G943A (p. G315S) from his mother (PMID 20056467) and C. G739A (p. G247S) from his father (PMID 18554280, 24753243) . Case 2 had a heterozygous mutation, c.454-2A＞G, in GCH-1 gene, which was identified to be from his father (PMID 10732814) . Case 3 had two mutations in TH1 gene, c.580+2T>C from her mother (novel mutation) and c.698G>A (p.R233H) from her father (PMID 9703425) . The mother of case 1 was pregnant again. Prenatal examination revealed that the fetus only carried c.G943A (p.G315S) from the mother. Three patients were treated with a small dose of madopar after diagnosis, and gradually increased to obtain the best effect. After 6-month follow-up, cases 1 and 2 recovered to normal, and case 3 showed significant improvement in dystonia, but left foot deformity. Conclusion DRD can start in infants and young children with atypical early symptoms. Genetic testing can make a definite diagnosis. The family that has proband should undergo prenatal examination.