抗肌萎缩蛋白病合并Klinefelter综合征一例及文献复习

Rare combination of dystrophinopathy and Klinefelter＇s syndrome in one patient

目的 总结一例抗肌萎缩蛋白病合并Klinefelter综合征患儿的临床特点,并结合文献进行分析.方法 北京儿童医院2013年3月就诊神经内科门诊的一例抗肌萎缩蛋白病合并Klinefelter综合征患儿,对其症状、体征、血清肌酸激酶水平、智力情况、性激素水平及基因诊断结果进行总结,并回顾既往国内外文献4例患儿资料.结果 患儿为8岁6个月男孩,自幼发育落后,行走不稳,8岁时出现运动能力倒退,渐加重.体格检查可见特殊面容、鸭步态、脊柱前突、Gower＇s征阳性、双侧腓肠肌假性肥大、肌力及腱反射减弱.血清肌酸激酶21 040 U/L,智能轻度缺损.基因学检查结果显示dystrophin基因外显子49～54缺失,且患儿2条X染色体均来自母方同一条同源染色体.结合既往报道4例患儿：5例患儿确诊年龄3岁6个月～18岁.1例无明显临床表现,为在家系筛查中发现,1例因行走爬楼困难就诊,余3例因发育落后就诊.2例患儿存阳性家族史.5例患儿均存腓肠肌肥大,部分患儿同时具有鸭步及Gower＇s征等典型体征.患儿身高均处于同年龄儿3～ 50百分位,2例合并特殊面容,4例完善睾丸容积测量为1 ～8 ml.4例完善智力测查存不同程度智力受损.4例血清肌酸激酶水平为2 469 ～24 750 U/L.1例为家系筛查中发现;3例应用病理方法确诊;1例应用多重连接探针扩增技术检测到dystrophin基因缺失而确诊.结论 抗肌萎缩蛋白病合并Klinefelter综合征患儿通常具有两种疾病的临床特征,同时完善dystrophin基因突变检测和染色体核型分析可明确诊断.

Objective To analyze clinical characteristics of a combination of dystrophinopathies and Klinefelter＇s syndrome （karyotype 47,XXY） in one patient.Method The patient was diagnosed as Duchenne muscular dystrophy （DMD） and Klinefelter＇s syndrome in Beijing Children＇s Hospital in March,2013.The clinical manifestations,physical examinations and laboratory test results were analyzed respectively.The clinical characteristics of four cases reported previously were analyzed as well.Result The 8.5 years old boy presented with symptoms of walking disorder and developmental delay.The patient had facial dysmorphism,waddling gait,Gower＇s manoeuvre and enlarged calves.Serum creatine kinase level was 21 040 U/L,and he had mild intellectual impairment.Deletions of exons 49-54 of the dystrophin gene were found.Gene dosage analysis revealed a heterozygous deletion in his mother.Five cases have been reported till now,their age ranged from 3.5 to 18 years; 3 of them were DMD,while the other 2 cases were Becker muscular dystrophy （BMD）.One of them,detected in pedigree study,whose weakness was minimal in contrast to the proband.The others came to the hospital because of walking disorder or developmental delay.All the patients had enlarged calves,some of them also had Gower＇s manoeuvre and waddling gait.The patients＇ height was between 3 rd and 50 th percentile,while 2 of them had facial dysmorphism.Some degree of mental impairment is usual.Their serum creatine kinase were 2 469-24 750 U/L.One of them was detected in pedigree study.Three of them were diagnosed by muscle biopsy,while in the other one mutation analysis was used.Conclusion The combination of dystrophinopathies and Klinefelter＇s syndrome is quite rare,and has clinical features of these two diseases.Mutation analysis （or muscle biopsy） and karyotype analysis can finally diagnose the syndrome.