Background: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with an extremely variable phenotype. In childhood NF1 can be associated with optic glioma and central precocious puberty; the latter is more common when the optic chiasm is affected. The mutational spectrum of the NF1 gene is wide and complex; R681X is a rare severe mutation of the NF1 gene known to cause truncation of neurofibromin, with only ten reported cases in the literature so far.
Case presentation: We describe a girl with NF1 associated with early central precocious puberty appearing at 2.5 years of age and optic glioma affecting the optic chiasm as seen on magnetic resonance imaging (MRI). Genetic analysis confirmed the presence of R681X. Therapy with a gonadotropin-releasing hormone agonist was instituted with good response to therapy. The lesions on MRI were stable and no significant vision impairment was present during the 6 years of follow-up.
Conclusion: Of the ten reported cases of NF1 due to R681X, one has presented with optic glioma and none with precocious puberty. Thus, to our knowledge, this is the first reported case of this mutation presenting with precocious puberty. We believe that this is a contribution to the few reports on the phenotype of this mutation and to the future elucidation of genotype-phenotype correlations of this disease.