Neurofibromatosis

Excerpt

Neurofibromatosis is an autosomal dominant genetic neurocutaneous disorder characterized by excessive nerve sheath tumor predisposition, most prominent in the nervous system and skin. This neurocutaneous disorder has 3 distinct types of neurofibromatosis: type 1 (NF1), type 2 (NF2), and schwannomatosis. NF1 and NF2 are the most common, while schwannomatosis is rare (see Image. Neurofibromatosis).

Neurofibromatosis Type 1 and 2

NF1, or von Recklinghausen disease, is characterized by multiple body organs with multiple (≥6) cafe-au-lait macules (CALM), neurofibromas of any type or plexiform neurofibroma, axillary or inguinal freckling, hamartomatous Lisch nodules of the iris, optic pathway glioma, and disease-specific bony dysplasia. In addition to benign and malignant tumor development, patients also have greater risks of other musculoskeletal, cardiovascular, and nervous system abnormalities. NF1 is caused by a loss-of-function mutation in 1 allele of the NF1 gene, resulting in a 50% loss of function of neurofibromin, a tumor suppressor protein ubiquitously expressed. According to the National Neurofibromatosis Foundation International Database, approximately 20% of children aged 0 to 19 develop plexiform neurofibromas. Plexiform neurofibromas are benign peripheral nerve tumors with a plexiform growth pattern. They are diffuse growths involving multiple nerves and plexi with significant morbidity.

NF2 has an autosomal dominant inheritance pattern and is characterized by the development of bilateral vestibular schwannomas and meningiomas. Notably, neurofibromas do not occur in this syndrome; therefore, the name NF2 is a misnomer. An international consensus has recommended the new and more accurate name of NF2-related schwannomatosis. NF1 and NF2 treatment involves clinical monitoring and medical intervention when appropriate.

Schwanomatosis

Schwanomatosis is the rarest of the 3 types of neurofibromatosis, with an incidence of 0.58 cases per 1,000,000 people. The presence of multiple nonintradermal peripheral and spinal schwanomas characterizes it. Localized or diffuse chronic pain or asymptomatic masses are common presentations. Vestibular schwannoma is uncommon in this entity. Schwannomatosis is mostly sporadic. Approximately 15% to 25% of these patients have inherited this disorder. SMARCB1 and LZTR1 are the 2 most common gene mutations, either spontaneous or inherited with reduced penetrance. The newly revised names for these entities are SMARCB1-related schwannomatosis and LZTR1-related schwannomatosis. Due to its rarity, schwanomatosis will not be elaborated on in this activity.