Chapter 5

■Neurofibromatosis type 1 (NF1) is an inherited disorder that predisposes a patient to acquired neoplasms.

■There are many challenges to the management of NF1 associated orbitofacial neurofibromas and optic pathway gliomas.

■New understanding of intracellular pathways, specifically the role of neurofibromin as a negative regulator of Ras, an intracellular signaling protein, may allow future treatment to target NF1-associated tumors.

■While chemotherapy protocols to treat optic pathway gliomas (OPGs) have been somewhat effective, the medical treatment of plexiform neurofibromas to date has been less successful.

■A multidisciplinary approach is essential for treating patients with NF1 and should include genetic counseling and testing for both patients and their families.

■Early intervention can better control expansion of soft tissues and possibly reduce bony orbital expansion.

■Periorbital surgical techniques for managing tumors involving the orbit and adnexal structures can often spare more invasive neurosurgical approaches in the orbitofacial rehabilitation of NF1 patients.

■Orbital exenteration can be avoided in almost every instance.

5.1Introduction

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder occurring with an estimated incidence of 1 in 3,000 live births [16]. The propensity for tumor progression and skeletal abnormalities in this disease present both functional and cosmetic challenges for both patients and the physicians treating them. This is most evident in patients disfigured by NF1 involving the orbits and face. This chapter summarizes the clinical findings, updates current clinical trials, and describes surgical techniques useful in the treatment of NF1 tumors involving the orbit and adjacent tissues.

5.2Nomenclature

The first published case report describing the findings in NF1 was published by Von Recklinghausen in1882 [43]. There have since been numerous terms used to describe

the involvement of the orbit and face. Orbitotemporal neurofibromatosis has been the most common [12]. Other terms are orbitopalpebral neurofibromatosis [35], orbitofacial neurofibromatosis [46], oculofacial neurofibromatosis [10], and cranio-orbital-temporal neurofibromatosis [18]. Orbitofacial neurofibromatosis is perhaps the most inclusive term for the oculoplastic surgeon since it highlights the potential involvement of NF1 tumors affecting not only the orbit, eyelids, and temporalis region but also facial structures above and below the orbits.

5.3Clinical Manifestations of NF1

NF1 is caused by a germline-inactivating mutation in the NF1 gene on chromosome 17 that results in deregulated cell growth. This abnormal growth manifests in various soft tissue and bony abnormalities, often producing major orbitofacial deformities [50]. The lesions most disfiguring in orbitofacial NF1 are neurofibromas and optic gliomas.