Martin Florence, Kana Veronika, Mori Andrea Capone, Fischer Dirk, Parkin Nicolas, Boltshauser Eugen, Rushing Elisabeth Jane, Klein Andrea
Department of Paediatric Neurology, Kantonsspital Winterthur, Winterthur, Switzerland,
Eur J Pediatr. 2014 Dec;173(12):1691-4. doi: 10.1007/s00431-014-2314-6. Epub 2014 Apr 8.
We describe a 5-year-old girl with marked hypotonia, poor feeding and reduced facial expression since birth. Congenital myopathy was suspected; muscle biopsy showed unspecific type 1 fibre predominance. The possibility of a ryanodine receptor 1 gene (RYR1)-associated myopathy was considered, but not further investigated. At the age of 2 years, she presented with exophthalmos. Brain MRI revealed optic pathway glioma. On clinical examination, she had six café-au-lait spots, thus fulfilling the diagnostic criteria for neurofibromatosis type 1 (NF1). The hypotonia was then attributed to NF1. At the age of 3 years, she developed scoliosis and had an unusually severe motor delay for NF1, as she was not able to walk independently. Dual pathology was suspected, and muscle MRI showed the typical pattern for RYR1-related myopathy. This was genetically confirmed with the discovery of two heterozygous mutations.
NF1 is one of the most frequent genetic diseases in children. RYR1-related myopathy is one of the most frequent causes of congenital myopathy. The combination of these two pathologies has not yet been described. In cases of unusual presentations or clinical course, the possibility of genetic "double trouble" should be considered.
我们描述了一名5岁女孩，自出生以来就有明显的肌张力减退、喂养困难和面部表情减少。怀疑为先天性肌病；肌肉活检显示以1型纤维为主，但无特异性。考虑到与兰尼碱受体1基因（RYR1）相关的肌病的可能性，但未进一步研究。2岁时，她出现眼球突出。脑部磁共振成像（MRI）显示视神经通路胶质瘤。临床检查发现她有6个咖啡牛奶斑，从而符合1型神经纤维瘤病（NF1）的诊断标准。于是，肌张力减退被归因于NF1。3岁时，她出现脊柱侧弯，并且对于NF1来说，她有异常严重的运动发育迟缓，因为她无法独立行走。怀疑存在双重病理情况，肌肉MRI显示出RYR1相关肌病的典型模式。通过发现两个杂合突变在基因上得到了证实。
NF1是儿童中最常见的遗传性疾病之一。RYR1相关肌病是先天性肌病最常见的病因之一。这两种病理情况的组合尚未见报道。在出现不寻常表现或临床病程的病例中，应考虑遗传“双重麻烦”的可能性。
