Division of Neuropediatrics and Muscle Disorders, University Children's Hospital Freiburg, Freiburg, Germany.
J Neurol Sci. 2010 Apr 15;291(1-2):79-85. doi: 10.1016/j.jns.2009.12.008. Epub 2010 Feb 8.
The broadwide spectrum of differential diagnoses of autosomal dominant muscular dystrophies in adults can be specified by additional features. The combination of late-onset muscular dystrophy, rimmed vacuoles and inclusion bodies in the muscle biopsy, and Paget's disease of bone suggests a mutation in the Valosin-containing protein gene (VCP, p97 or CDC48) even without dementia. We report on a German family with late-onset autosomal dominant muscular dystrophy starting in the pelvic girdle about age 40years, a subsequent rapidly-progressing course, high alkaline phosphatase and Paget's disease of bone. Clinical examination revealed no cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. Mutations in VCP, filamin C, desmin, alphaB-crystallin, ZASP and myosin heavy chains 2 and 7 as well as the genes for facioscapulohumeral muscular dystrophy, Myotonic Dystrophy I and II, and LGMD1A-G were excluded by a combination of linkage analysis and direct sequencing. The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia.
常染色体显性遗传的成年型肌肉萎缩症的广泛鉴别诊断可以通过其他特征来确定。迟发性肌肉萎缩症、肌活检中的边缘空泡和包涵体以及 Pagets 骨病的组合提示存在 VCP（p97 或 CDC48）基因突变，即使没有痴呆症也是如此。我们报告了一个德国家族，其成员患有迟发性常染色体显性遗传的肌肉萎缩症，发病年龄约为 40 岁，骨盆带开始出现症状，随后病情迅速进展，碱性磷酸酶升高，伴有 Pagets 骨病。临床检查未发现认知障碍。组织学检查显示肌病改变，伴有肌活检中的边缘空泡和包涵体。通过连锁分析和直接测序相结合，排除了 VCP、细丝蛋白 C、结蛋白、αB-晶体蛋白、ZASP 和肌球蛋白重链 2 和 7 的突变，以及面肩肱型肌营养不良症、强直性肌营养不良症 I 和 II 以及 LGMD1A-G 的基因。本研究提示，一种尚未确定的遗传缺陷可导致常染色体显性遗传肌肉疾病伴 Pagets 骨病但无痴呆症。
