ESPE Abstracts

Background/Objectives: Neurofibromatosis 1 (NF1) is a dominantly inherited genetic disorder, caused by germline pathogenic variants in NF1 gene. The protein product of NF1 is neurofibromin, which acts as a tumor suppressor protein regulating the RAS signaling pathway. We describe the mutational spectrum and clinical presentation of NF1 children, which will aid the understanding of genotype-phenotype correlations.

Methods: We collected clinical characteristics and imaging studies of 225 children with not only clinical diagnosis of NF1 but also germline variants in NF1 by genetic testing. At last, we analyzed the Genotype–phenotype correlations using Excel and Spss software.

Results: 225 NF1 children with a mean age of onset of 5.60 years were included. 182 different gene variants were identified,64.9% of which were de novo variants. 6 patients had the same gene variants c.1466A>G, half of them had growth delay. More than 40 variants were previously unreported. 58 children had short stature. The causes included growth hormone deficiency, vitamin D deficiency, and scoliosis. 47 patients had unidentifiable bright objects UBO）, 33 patients had scoliosis, 27 patients had plexiform neurofibromas, 6 patients had epilepsy, 8 patients had precocity, four of which had OPG, and 4 patients had JMML. We analyzed these children's height of different ages, and found that the standard deviation scores of height (HtSDS) was -1.24±1.49SD. Boys were shorter with height -1.60±1.28SD. There was a statistical difference between boys and girls.

Conclusion: Our study suggested some genotype–phenotype correlations within NF1 children in China, contribute to the diagnosis, treatment, management and follow-up of NF1 children.