儿童Schwartz—Jampel综合征一例并文献复习

Clinical and genetic features of Schwartz-Jampel syndrome in a Chinese child： case report and literature review

目的总结一例儿童Schwartz—Jampel综合征的临床及基因突变特征并进行文献复习。方法回顾性分析2010年8月首次就诊于北京儿童医院神经内科的一例Schwartz—Jampel综合征患儿的临床及基因突变分析资料，并进行文献复习。以“Schwartz—Jampel综合征”“Schwartz—Jampel syndrome”“Schwartz—Jampel syndrome and HSPG2”为检索词，检索CNKI、万方数据库、PubMed数据库（建库至2015年7月），选取文中报道进行了HSPG2基因检测以及临床资料完整者的文献。结果患儿女，3岁7月龄。患儿于生后8个月出现肌肉强直，1岁独走时双下肢僵直，双足外翻，行走缓慢，易摔倒。2岁不会双腿交替上楼梯，3岁不会连续跳跃。体格检查发现患儿面部表情少，口唇发紧，张口小，小下颌，耳位低，招风耳，全身肌肉强直，四肢肌丘形成，走路姿势僵硬，双足稍平行，不能走直线。辅助检查：肌酶均升高，肌电图示肌强直电位，四肢X线片示软骨发育不良，脊柱CT三维重建示颅底骨质向上凹陷、寰枢椎半脱位。行康复治疗，并加用卡马西平口服，末次随访为患儿8岁时，停用卡马西平1年，患儿肌强直症状较首次就诊时无明显变化。基因分析证实患儿HSPG2基因存在复合杂合突变，第78外显子c．10776delT的移码突变，导致蛋白质改变为P．A1a3592fsX6；第45内含子c．5702-5G〉A的杂合突变，靠近剪接位点突变。检索符合条件的中文文献0篇，英文文献7篇。已报道34个基因突变，11个缺失或插入突变，12个剪接位点突变，8个错义突变，5个无义突变。4例患者只发现1个突变位点，未发现热点突变或创始人突变，无明确基因型一表型关系。结论Schwartz—Jampel综合征为罕见的缓慢进展的常染色体隐性遗传病，是由于HSPG2基因突变致病，本病例第78外显子e．10776delT的移码突变和第45内含子C．5702-5G〉A均为未报道的新突变。本例为首例明确基因突变的中国儿童Schwartz—Jampel综合征患者。

Objective To investigate the clinical and genetic features of a Chinese girl with Schwartz-Jampel syndrome （SJS）. Method To analyze the clinical and genetic data of a girl with Schwartz- Jampel syndrome who was sent to neurology outpatient department of Beijing Children＇s Hospital in Auguest of 2010. Reports on Schwartz-Jampel syndrome published until July of 2015 were searched and the clinical and genetic characteristics of reported cases were summarized. Result At g months after birth, the girl showed myotonia; at 1 year old when she was walking alone she had myotonia of lower limbs, both feet evaginated, walked slowly and was prone to fall. At 2 years of age, she could not climb up stairs, at 3 years she could not jump continuously. At 3 years and 7 months of age when the girl was taken to neurology outpatient department, on examination, she had a dull facial expression, rigid lips and could not fully open her mouth, a micromandible, low-set and prominent ears, systemic muscle rigidity, there were muscular nodes formation on the limbs and gait stiffness. She had high level of creatine kinase and atlanto-axial joint subluxation on cervical CT reconstruction. She also had spontaneous myotonia-like discharges on needle electromyography （NEMG）. X-ray of limbs showed metaphyseal dysplasia. The patient was treated with neurologic rehabilitation and earbamazepine. The myotonia at the last follow-up at her 8 years of age was the same as at the onset. On her HSPG2 gene, two novel heterozygous mutations c. 10776delT on exon 78 and c. 5702-5G 〉 A on intron 45 were found, c. 10776delT resulted in the amino acid change on p. Ala3592fsX6 and c. 5702-5G 〉 A maybe changed protein splicing. No reports were found among Chinese journals, while 7 reports were found in English literature. The total 34 mutations were known in reviewed reports, which included eleven deletion or insertion, twelve splice site, eight missense, and three nonsense mutations. Four patients had a single mutation. No definite genotype-phenotype correlation was identified. Conclusion Schwartz-Jampel syndrome is a rare autosomal-recessive hereditary disease appears to be slowly progressive, in which distinctive clinical features were induced by HSPG2 gene mutation. We reported the c. 10776delT on exon 78 and c. 5702-5G 〉 A on intron 45 which were not reported previously. This is the first report of Schwartz-Jampel syndrome of which genetic mutations was identified in a Chinese child.