Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy
Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy
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DOI：
10.1016/j.pediatrneurol.2015.11.004
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发表时间：
2016-02-01
影响因子：
3.8
通讯作者：
Fiorillo, Chiara
中科院分区：
文献类型：
--
作者：
Papa, Riccardo;Madia, Francesca;Fiorillo, Chiara
背景技术背景：杜氏肌营养不良症（DMD）的女性携带者，虽然通常没有症状，但高达17%的时间会出现肌肉无力，三分之一的人会出现心脏异常或认知障碍。DMD携带者在儿童时期的临床特征知之甚少。患者：我们描述了一组儿童DMD携带者，提供了临床、遗传和组织病理学特征，平均随访7年。结果：15名女性DMD突变（年龄范围5至18岁）。7例患者（46%）出现临床明显症状和体征，如肢带无力、步态异常和运动不耐受。另外8名患者（53%）由于偶然发现肌酸激酶水平升高而进行了评价。所有患者的肌酸激酶水平均升高，范围为392 - 13，000 U/L。在8例患者（53%）中观察到小腿肥大。无患者发生呼吸或心脏受累。最常见的并发症是脊柱侧凸（46%）。4名患者（29%）还表现出轻微的学习障碍或行为问题。我们在一半的患者中进行了肌电图检查，显示4例（53%）有肌病。肌肉活检显示，马赛克减少肌营养不良蛋白在9个可用的情况下。DMD基因突变以缺失型为主（71%），5例患者（36%）出现阅读框丢失。经历最严重病程的三名患者要么受到无意义突变的影响，要么受到移码突变的影响。结论：我们的分析表明，DMD基因突变可能被怀疑在一个女孩的肌酸激酶水平持续升高。在肌电图检查中发现脊柱侧凸、小腿肥大或肌病也是有帮助的，肌肉活检也是提示性的。DMD携带者在儿童时期应注意细微的矫形和精神并发症。
BACKGROUND: Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinical features of DMD carriers during childhood are poorly known. PATIENTS: We describe a cohort of pediatric DMD carriers, providing clinical, genetic, and histopathologic features, with a mean follow-up of 7 years. RESULTS: Fifteen females with a DMD mutation (age range 5 to 18 years) were included. Seven patients (46%) presented with clinically evident symptoms and signs such as limb girdle weakness, abnormal gait, and exercise intolerance. The other eight patients (53%) were evaluated because of an incidental finding of elevated level of creatine kinase. Creatine kinase level was elevated in all, ranging from 392 to 13,000 U/L. Calf hypertrophy was observed in eight patients (53%). No patient developed respiratory or cardiac involvement. The most frequent complication was scoliosis (46%). Four patients (29%) also presented minor learning disabilities or behavioral problems. We performed electromyography in half of patients, showing myopathic pattern in four (53%). Muscle biopsy revealed a mosaic reduction of dystrophin in nine available cases. DMD gene mutations were mostly deletions (71%), resulting in loss of reading frame in five patients (36%). The three patients who experienced the most severe disease course were affected either by a nonsense or frameshift mutation. CONCLUSIONS: Our analysis suggests that DMD gene mutations may be suspected in a female child with persistently elevated levels of creatine kinase. Evidence of scoliosis, calf hypertrophy, or myopathic pattern at electromyography may also be helpful, and muscle biopsy is always indicative. DMD carriers should be followed for subtle orthopedic and psychiatric complications during childhood.