LG-55: CASE REPORT OF AN OPTIC PATHWAY GLIOMA IN A PATIENT WITH LEGIUS SYNDROME

Legius syndrome (OMIM#611431) is an autosomal dominant condition caused by a mutation in the SPRED1 gene, which codes for the spred-1 protein, a negative regulator of the RAS-mitogen activated protein kinase (RAS-MAPK) signaling pathway. Disruption of the RAS-MAPK pathway results in numerous genetic syndromes, often with overlapping phenotypes, referred to as “RASopathies”. Many of the RASopathies, including neurofibromatosis 1 (NF1), have a well-documented predisposition for certain tumors and hematologic malignancies. Legius syndrome was initially described as a NF1-like syndrome because these patients present with multiple café-au-lait macules, intertriginous freckling and macrocephaly but do not have typical NF1-associated features such as neurofibromas, Lisch nodules or optic pathway gliomas. Legius syndrome has therefore been considered less severe and these patients do not undergo routine ophthalmological screening examinations. We report a 2-year-old female who initially presented with rotary nystagmus and vision loss in the right eye. MRI brain demonstrated a large suprasellar mass arising from the optic chiasm. Because she was also noted to have numerous café-au-lait macules, she initially received a clinical diagnosis of NF1. Molecular testing demonstrated normal NF1 gene testing but demonstrated a deletion involving exons 2-5 on the SPRED-1 gene, consistent with Legius syndrome. Stereotactic needle biopsy of her tumor was performed and pathology was consistent with a low-grade glioma with piloid features. This is the first documented case of an optic pathway glioma in a patient with Legius syndrome, suggesting the disorder may not be as benign as initially perceived and that ophthalmologic screening may be warranted.