Background Neurofibromatosis type 1 (NF1) affects 1 in 2500 people, and 15% of these may develop an optic pathway glioma (OPG). OPGs behave differently in NF1, and, given their frequency, surveillance is important. However, this is difficult because of the additional complications these patients may have, such as learning difficulties. Management is also different given that NF1 results from loss of function of tumour suppressor gene. A genotype–phenotype correlation may help to determine who is at risk of developing these tumours, aid focused screening, and shed light on response to treatments.

Methods As part of a long-term follow-up study of patients with NF1 OPGs, the authors assessed genotype–phenotype correlation. Fluorescein in situ hybridisation was performed to identify large deletions, and then a full gene screen for mutations, by denaturing high-performance liquid chromatography.

Results 80 patients with NF1 OPGs were identified, and molecular analyses were performed in a subset of 29. A clustering of pathogenic changes in the 5′ tertile of the gene was found. The authors combined these results with those for another two NF1 OPG cohorts and collectively found the same trend. When compared with a control population of NF1 patients without an OPG, the OR of a mutation being present in the 5′ tertile was 6.05 (p=0.003) in the NF1 OPG combined cohorts.

Conclusion It is possible that genotype is a significant determinant of the risk of development of OPGs in NF1.