UBA5基因变异相关婴儿痉挛症患儿表型及基因型特点

Phenotype and genotype characteristics of infantile spasm related to UBA5 gene mutation

目的分析UBA5基因变异相关婴儿痉挛症(IS)的临床表型及基因型特点。方法回顾性分析2017年3月至2019年6月北京大学第一医院儿科诊治的4例UBA5基因变异所致IS的患儿资料,对其临床表现、脑电图、头颅影像学、治疗及随访结果进行总结。结果 4例(男3例、女1例)均确诊IS并携带UBA5基因复合杂合变异,检测到6种变异位点,其中5种为国际上尚未报道的新变异。4例均以痉挛发作起病,起病年龄为出生1 d~8个月;2例在病程中出现局灶性发作。4例脑电图均监测到高度失律及痉挛发作。完成头颅磁共振成像检查3例中2例为非特异性异常,1例正常。4例起病前均发育落后,起病后有不同程度倒退且进步缓慢;1例小头畸形,3例肌张力高。末次随访年龄为7个月~6岁4个月,4例均接受多种抗癫痫药物联合治疗且发作均未控制。结论 UBA5基因变异相关IS患儿起病年龄较早,常伴发育落后、小头畸形、肌张力异常,癫痫发作常为难治性。

Objective To analyze the clinical phenotype and genotype characteristics of infantile spasm(IS)associated with UBA5 gene mutation.Methods Four cases of IS caused by UBA5 gene variation diagnosed at the Department of Pediatrics,Peking University First Hospital from March 2017 to June 2019 were retrospectively analyzed.The clinical manifestations,electroencephalogram(EEG),brain magnetic resonance imaging(MRI),treatment,and follow-up results were summarized.Results In this study,4 cases(3 males and 1 female)were clinically diagnosed with IS and carried complex heterozygous variation of UBA5 gene.Genetic analysis confirmed that a total of 6 different mutation sites were found,five of which were unreported.All the 4 cases presented with epileptic spasms at the age of 1 d to 8 months after birth,and 2 cases had focal seizures during the course of disease.The EEG of 4 cases showed hypsarrhythmia and cluster or isolated epileptic spasms were detected.Of the 3 patients who had brain MRI results,2 cases showed nonspecific abnormalities and 1 case was normal.All the 4 patients had developmental delayed before seizure onset,and regressed to varying degrees and made slow progress after onset.One case had microcephaly,and 3 cases had hypertonia.At the last follow-up,the age of the 4 patients ranged from 7 months to 6 years and 4 months.All 4 patients were treated with multiple antiepileptic drugs,but none of them were under control.Conclusions Children with IS associated with UBA5 gene variation have an early onset age,often accompanied by developmental delayed,microcephaly,dystonia,and refractory seizures.