Orbital/Periorbital Plexiform Neurofibromas in Children with Neurofibromatosis Type 1

Abstract

Children and adults with Neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas involving the eyelid, orbit, periorbital and facial structures (termed OPPN) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. Despite NF1 being a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. While medical and surgical interventions have been reported, there are no agreed upon criteria for when OPPN require therapy and which treatment produces the best outcome. Since a multi-disciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual and or aesthetic sequelae complicates the design of evidence based studies and feasible clinical trials. In September 2013, a multi-disciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. This consensus statement provides recommendations for ophthalmologic monitoring and outlines treatment indications, forthcoming biologic therapy, while also discussing challenges to performing clinical trials in this complicated condition.

Creating a comprehensive research strategy for cutaneous neurofibromas

“…[8][9][10][11] A great deal is understood about NF1 and the cellular and molecular effects of the absence of neurofibromin and there is exciting development of therapies for NF1-associated tumors such as pNF and optic pathway gliomas. 12,13 However, relatively little is known about cNF. This is partially because cNF are unlikely to cause fatal complications or severe neurologic morbidity.…”

Ocular Findings in Neurofibromatosis

“…Sphenoid wing dysplasia can be found in patients with OPPN affecting the same side and usually present with proptosis and pulsatile exophthalmos. Plexiform neurofibroma is a highly recurrent tumor, especially in orbito-facial area and in younger patients [17][18][19].…”

“…A high-resolution magnetic resonance imaging (MRI) with and without contrast of the brain and orbits should be performed in all NF-suspected patients to confirm the diagnosis and to monitor for the progression. CT scan should be avoided if possible, because of its radiation and the risk of malignant transformation of neurofibroma [19].…”

“…The most common indications for surgical debulking are cosmetic, decreased vision, progressive involvement of a vital structure, and functional deficits. Any significant increase in the growth rate of neurofibroma that is unusual for the patient age should be worrisome for malignant transformation [19].…”

The concept of type 2 segmental mosaicism, expanding from dermatology to general medicine

“…) are sometimes described as ‘elephantiasis neuromatosa’ . Moreover, T2SM may involve the brain, eye and orbita, bones and joints, parotis, thyroid, larynx, trachea, lung, heart, oesophagus, upper gastro‐intestinal tract (Fig. ), rectum, liver, gall bladder, pancreas, retroperitoneum and bladder …”