以癫痫为首发症状的小儿结节性硬化症二例及其基因突变分析

Genetic analysis of tuberous sclerosis complex in two kids initiated by epilepsy

目的探讨以癫痫为首发症状的小儿结节性硬化症的临床、头颅影像及基因突变特点,以提高临床医生对该病的认识。方法以2例就诊于山西省儿童医院神经内科门诊的结节性硬化症患者(系姐妹)为研究对象,回顾性收集其临床及实验室资料,电话追踪其他家庭成员患病情况后绘制家系图谱,并对2例患者及其父母进行相关致病基因突变筛查。结果先证者1、2均以癫痫为首发症状,且发病年龄在1岁以内,伴皮肤色素脱失斑;其中先证者2表现为婴儿痉挛,伴发育迟缓。影像学检查显示颅内结节性钙化影,该家系受累2代,共3例患者,均为女性。基因测序结果在TSC2基因上发现同一个无义突变c.4174C>T(p.Arg1392Ter),为杂合性突变,其母亲亦携带此突变。结论对以癫痫为首发症状,同时伴有特征性皮肤改变及发育迟滞的患儿,当其头颅影像学提示颅内结节性钙化灶时,应高度怀疑结节性硬化症可能。通过相关基因突变筛查可明确基因突变位点,从基因水平进行明确诊断。

Objective To investigate the clinical, neuroimaging and genetic characteristics of tuberous sclerosis complex（TSC） in 2 kids initiated by epilepsy. Methods The clinical data of two patients who were diagnosed TSC in Children＇s Hospital of Shanxi Province were summarized. The condition of other members were traced and their pedigree trees were drawn. And the DNA sequences of TSC1 and TSC2 genes were investigated for mutations, then the DNA samples of the patients and the patient＇s parents were tested with Sanger sequencing. Results The proband 1 and 2 went to our clinic for the reason of epilepsy, the proband 2 showed infantile spasms, with growth retardation. Neuroimaging examination noted intracranial nodular calcification. The patients had family history, 3 female patients in total. Gene mutation analysis of TSC2 gene demonstrated the c.4174CT mutation in patients, and the mutation was inherited from mother. Conclusion For young children with epilepsy as the first symptom, accompanied by growth retardation, facial angiofibroma or hypopigmented macule and other skin features, when the neuroimaging examination showed intracranial nodular calcification should be highly suspected of tuberous sclerosis complex. Gene analysis of TSC1 and TSC2 contribute to the diagnosis of this disease.