Neurofibromatosis type 1 (NF1) with an unusually severe phenotype due to digeny for NF1 and ryanodine receptor 1 associated myopathy

作者：Martin Florence; Kana Veronika; Mori Andrea Capone; Fischer Dirk; Parkin Nicolas; Boltshauser Eugen; Rushing Elisabeth Jane; Klein Andrea^*

来源：European Journal of Pediatrics, 2014, 173(12): 1691-1694.

DOI：10.1007/s00431-014-2314-6

• Neurofibromatosis type 1
• Ryanodine receptor 1
• Myopathy
• Dual pathology
• Central core disease

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 caf,-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. Conclusion: 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 %26quot;double trouble%26quot; should be considered.

• 出版日期2014-12