A novel stop-gain NF1 variant in neurofibromatosis type 1 and bilateral optic atrophy without optic gliomas.

Background: Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily affects the skin and peripheral nervous system and is caused by chromosomal abnormalities and mostly truncating variants in the NF1 gene. Ocular complications such as Lisch nodules and optic pathway gliomas (OPGs) can occur in NF1 patients. Herein, we report a novel NF1 variant in an NF1 patient with bilateral optic atrophy.

Methods: Ophthalmological examinations and genetic analyses were performed using targeted next-generation sequencing (NGS).

Results: A 14-year-old girl diagnosed with NF1 visited our hospital with decreased visual acuity (VA). The patient had no family history of NF1 or visual impairment. Brain and orbital magnetic resonance imaging revealed no remarkable findings. Ophthalmoscopy revealed temporal pallor of the optic discs, which was confirmed by optical coherence tomography findings of significant thinning of the circumpapillary retinal nerve fiber layer in both eyes. At 23 years of age, the decimal-corrected VA had deteriorated to 0.2 in the right eye and 0.1 in the left eye. Additionally, the targeted NGS panel revealed a novel heterozygous stop-gain variant (p.Tyr628Ter) in the NF1 gene; however, no pathogenic variants in OPA1 or the mitochondrial DNA were identified.

Conclusions: A patient with NF1 without OPGs developed bilateral optic atrophy and carried a novel de novo stop-gain variant of NF1. Although the relationship between NF1 variants and bilateral optic atrophy remains unclear, further investigations are required.