FRRS1L基因突变致发育性癫痫性脑病伴运动发育障碍1例并文献复习

Developmental and epileptic encephalopathy with dyskinesia caused by the FRRS1L gene mutation:a case report and literature review

对2022年6月徐州医科大学附属徐州儿童医院收治的1例FRRS1L基因突变导致的发育性癫痫性脑病(DEE)伴运动发育障碍患儿的临床特征及基因突变特点进行回顾性分析。患儿,男,1岁9个月,自幼发育迟缓,6月龄出现肌张力减低,1岁7月龄出现癫痫发作(局灶阵挛发作),多种抗癫痫发作药物治疗不能控制,随着癫痫发作开始出现发育倒退和手足异常运动。家系全外显子组测序显示患儿FRRS1L基因存在2个杂合变异(错义突变和缺失突变),其中错义突变系母源性c.754C>T(p.R252C),位于第4号外显子;缺失突变系父源性c.438_c.459del(p.I146fs*4),位于第2号外显子,构成复合杂合突变。共检索到国外文献6篇(31例患儿),临床表现与本例患儿相似,但基因型不同,均为纯合突变。FRRS1L基因突变可导致DEE,为常染色体隐性遗传,婴幼儿期起病的难治性癫痫发作,伴随发育倒退和明显的过度运动是其典型特征,远期预后不良。

The clinical characteristics and gene mutation profiles of a child who was treated in Xuzhou Children′s Hospital,Xuzhou Medical University in June 2022 due to developmental and epileptic encephalopathy(DEE)combined with dyskinesia caused by the FRRS1L gene mutation was analyzed retrospectively.A male case 1 year and 9 months old presented developmental delay since childhood,hypotonia at the age of 6 months,treatment-resistant seizures(focal clonic seizures)at the age of 1 year and 7 months that were unable to be controlled by antiepileptic drugs,and developmental regression and abnormal movements of the hands and feet during the attack.Whole exome sequencing showed 2 heterozygous variants(missense mutation and deletion mutation)in the FRRS1L gene of the child.The missense mutation c.754C>T(p.R252C)located in the 4th exon was inherited from his mother,and the deletion mutation c.438_c.459del(p.I146fs*4)located in the 2th exon was inherited from his father,thus constituting a compound heterozygous mutation.Through literature review,all 6 relevant literatures involving 31 children with DEE were published in foreign countries.They presented similar clinical manifestations to this case,but the genotypes were different,all of which were homozygous mutations.The FRRS1L gene mutation can lead to DEE,which is characterized by the autosomal recessive inheritance pattern,refractory epilepsy onset in infancy,developmental regression and prominent dyskinetic movements with hyperkinesia,and poor long-term prognosis.