American Journal of Medical Genetics 122A:95–99 (2003) Optic Pathway Gliomas in Neurofibromatosis Type 1: The Effect of Presenting Symptoms on Outcome Allison King, 1 Robert Listernick, 2 Joel Charrow, 3 Linda Piersall, 4 and David H. Gutmann 5 * 1 Division of Pediatric Hematology and Oncology, St. Louis Children’s Hospital, St. Louis, Missouri 2 Division of General Academic Pediatrics, The Children’s Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 3 Division of Genetics, The Children’s Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 4 Division of Pediatric Genetics, St. Louis Children’s Hospital, St. Louis, Missouri 5 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri Children with neurofibromatosis type 1 (NF1) may present with optic pathway gliomas (OPG) that can progress to visual loss or other neurologic symptoms. These tumors may become evident either as a result of patient signs or symptoms or as an incidental finding on ‘‘baseline’’ neuroimaging studies. In an attempt to determine if there were differences between symptomatic and asym- ptomatic children with OPG, a retrospective cohort study of ninety children with NF1 and OPG was performed using data from two large NF1 referral centers. Age at diagnosis, presenting symptoms, tumor location, asso- ciated features, and clinical response were assessed for children who were initially symptomatic from their OPG (n ¼ 51) and compared to similar data of asymptomatic children whose tumors were incidentally discovered by MRI (n ¼ 39). There were no differences in age at presentation, tumor location, NF1-associated symptoms, or clin- ical response between the groups. Initially symptomatic children were much more likely to require treatment (OR: 14.8, 95% CI [1.9–116.7]) than those with incidentally discovered, asymptomatic OPG. Although 36% of OPG were diagnosed in children over the age of 6 years, none received prior neuro- imaging and only two children had previ- ously normal eye examinations, suggesting that the vast majority of OPG in this group were longstanding, undiagnosed tumors. Based on these findings, we do not advocate ‘‘baseline’’ MRI in children with NF1, but strongly recommend that all children of the age 10 years and younger with NF1 have com- plete annual ophthalmologic evaluations. ß 2003 Wiley-Liss, Inc. KEY WORDS: neurofibromatosis 1; optic pathway glioma; pilocytic astrocytoma; brain tumor INTRODUCTION Neurofibromatosis 1 (NF1) is a common autosomal dominant tumor predisposition syndrome that affects 1 in every 3,500 people worldwide [Friedman et al., 1999]. Individuals with NF1 are prone to the development of benign and, less frequently, malignant tumors [Matsui et al., 1993]. Most adults with NF1 will develop a benign tumor composed mainly of Schwann cells and fibroblasts associated with nerve sheaths, termed a neurofibroma. However, neurofibromas are less frequently encoun- tered in children with NF1. In contrast, 15–20% of children with NF1 will develop a brain tumor. Typically, these brain tumors are low-grade pilocytic astrocytomas arising in the optic nerve and chiasm, but may also be seen in the hypothalamus, brainstem, and cerebellum [Lewis et al., 1984; Lund and Skovby, 1991; Listernick et al., 1994, 1995; Pascual-Castroviejo et al., 1994; Habiby et al., 1995; Janss et al., 1995; Molloy et al., 1995; Vinchon et al., 2000]. Optic pathway gliomas (OPG) are classified by the World Health Organization (WHO) as grade I ne- oplasms that presumably arise from supporting astro- cytes in the optic nerve [Rubenstein, 1988; Kleihues and Cavanee, 2000]. Microscopically, these tumors are composed of proliferating glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes with char- acteristic eosinophilic Rosenthal fibers. NF1-associated pilocytic optic gliomas are histologically identical to pilocytic astrocytomas that occur elsewhere in the *Correspondence to: David H. Gutmann, M.D., Ph.D., Depart- ment of Neurology, Box 8111; 660 S. Euclid Avenue, St. Louis, MO 63110. E-mail: gutmannd@neuro.wustl.edu Received 14 October 2002; Accepted 18 February 2003 DOI 10.1002/ajmg.a.20211 ß 2003 Wiley-Liss, Inc.