Neurofibromatoses: II linical recommendations for the diagnosis, treatment and multidisciplinary monitoring of patients with neurofibromatosis type 2 and schwannomatosis

Abstract

Neurofibromatosis type 2 is a neurocutaneous disease with an autosomal dominant pattern of inheritance. The NF2 gene is a tumor suppressor gene located on chromosome 22q12.1 and encodes the protein called merlin or schwannomin. Neurofibromatosis type 2 is characterized by the development of schwannomas of cranial nerves (usually bilateral involvement of the eighth nerve), spinal and peripheral nerves, multiple meningeomas, ependymomas, and ophthalmological changes (presenile cataract). The onset of neurofibromatosis type 2 symptoms occurs in the second and third decades of life. In about 10% and 18% of patients, they become evident at 10 and 15 years of age, respectively. There is currently good agreement on the criteria for the diagnosis of neurofibromatosis type 2 and follow-up protocols for neurofibromatosis type 2 affected/suspected and at risk subjects. Patients with neurofibromatosis type 2 should be periodically re-evaluated by a multidisciplinary medical team familiar with the disease. Longitudinal care includes the following: detailed medical history/genetic counseling/DNA analysis (at diagnosis), clinical assessment (dermatological, neurological, and ophthalmological (yearly); audiological tests with audiometry and brain stem auditory evoked response (BAER) (yearly); and brain and full spine magnetic resonance imaging (yearly). In first degree relatives of neurofibromatosis type 2 patients (at risk subjects), clinical monitoring includes the following: ophthalmological examination in the first two years of life (for asymptomatic congenital cataract); DNA analysis; clinical assessment (neurological, ophthalmological, and audiological) until the teens; and certainly brain and full spine magnetic resonance imaging at 15 and 30 years. If the results of these examinations are normal, follow-up can cease. The mainstay of treatment of NF2 complications is surgical removal of symptomatic tumors. Schwannomatosis is a third form of neurofibromatosis characterized by multiple schwannomas of cranial, spinal and peripheral nerves, but no bilateral vestibular schwannomas. The gene for schwannomatosis, called INI1/SMARCB1, is localized on chromosome 22 near the NF2 gene. In the pathogenesis of schwannomatosis, the most probable joint roles have INI1/SMACB1, NF2 gene, and other undetected genes. The disease begins to manifest itself clinically in young adulthood.