康健捷， 邓兵梅， 黎振声， 杨红军， 彭凯润， 王伟民

肯尼迪病患者的临床表型与基因型分析

康健捷1， 邓兵梅1， 黎振声2， 杨红军1， 彭凯润1， 王伟民3

目的探讨肯尼迪病(Kennedy’s disease，KD) 患者的临床特征和基因特点，以加强对KD的认识，减少误诊漏诊率。方法纳入2013年1月～2017年4月广州军区广州总医院神经内科收治的8例经基因确诊的KD患者，分析其临床特征、实验室检查、肌电图、神经电图和基因特点，使用肌萎缩侧索硬化症评分量表(amyotrophic lateral sclerosis rating scale，ALSFRS) 作为运动功能量表进行病情评估，分析临床特征及其与CAG重复序列数目的关系。结果所有患者均为成人发病，平均年龄为(36.63±4.14)岁，确诊病程平均为(12.13 ±3.44) y，均表现为四肢无力和肌肉萎缩，6例出现舌肌萎缩和构音障碍、肢体震颤、口周面肌束颤，4例性功能下降，6例乳腺发育。实验室检查结果7例肌酸激酶(creatine kinase，CK) 增高，8例甘油三酯增高，6例尿酸增高，2例睾酮增高。肌电图提示所有患者均表现为广泛神经源性损害，运动神经和感觉神经动作电位波幅降低，部分神经传导速度下降。AR基因CAG重复序列的重复次数为44～58次，CAG拷贝数与发病年龄呈负相关 (r=-0.753，P=0.031)，与ALSFRS评分呈负相关 (r=-0.733，P=0.039)，与CK 水平无关(r=0.250，P=0.550)。结论KD的临床特点为缓慢进展的延髓和脊髓肌肉萎缩无力，伴有肢体震颤、面肌束颤，部分可有内分泌功能及代谢紊乱。CAG 拷贝数越多，则发病年龄越早，运动功能评分越低。CAG拷贝数可作为KD病情的预测指标。

肯尼迪病； 基因诊断； 临床特点； 雄激素受体基因； 肌萎缩侧索硬化症评分量表

Abstract：ObjectiveTo strengthen the understanding of KD and avoid delayed diagnosis，we analyzed clinical，laboratory，electrophysiological and genetic characteristics of KD cases.MethodsEight cases diagnosed by gene as KD patients，were admitted for the study during January 2013 to April 2017.In this study，we analyzed the clinical manifestations，laboratory examination，EMG and genetic characteristics and used ALSFRS as motor function scores for condition assessment. The correlation between clinical features and CAG repeat size was analyzed．ResultsAverage age of onset was (36.63 ± 4.14) years and the average confirmed course were (12.13 ±3.44)years. Clinical features included medulla oblongata and spinal muscular atrophy and weakness in all eight cases，limbs tremor、perioral muscles twitch and gynecomastia in six cases，sexual dysfunction in four cases. Some patients had increased endocrine symptoms and metabolic disorders. EMG detected a widespread neuronal damage in all cases，and the sensory conductions were abnormal besides the motor conductions．The CAG repeat number in AR gene was from 44 to 58，respectively．The copy number of (CAG) n was negatively correlated with the onset age (r=-0.753，P=0.031) and the ALSFRS score (r=-0.733，P=0.039). The copy number of (CAG) n was independent of CK level(r=0.250，P=0.550).ConclusionKD is mainly presented with spinal and bulbar muscle atrophy and weakness，associated with endocrine and metabolic disturbance. The more copies，the early the onset and the lower the motor function score. The copy number of (CAG) n is valuable for assessment of KD.

Keywords： Kennedy’s disease； Clinical features； Gene analysis； Androgen receptor gene； Amyotrophic lateral sclerosis rating scale

肯尼迪病(Kennedy’s disease，KD)是一种晚发的X染色体连锁隐性遗传性神经系统变性疾病。……