pediatrics
Neurofibromatosis
Types of Neurofibromatosis
 are terminologies recommended by the International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) because they better reflect the updated criteria for these disorders that incorporate clinical features and genetic testing ( Types references ). (See also table Neurofibromatosis type 1 (NF1, or von Recklinghausen disease) is most prevalent, occurring in 1 of 4650 people in a study done in the United Kingdom ( Types references ). It causes neurologic, cutaneous, and sometimes soft-tissue or bone manifestations. The NF2-related schwannomatosis (NF2) accounts for 10% of cases, occurring in about 1 of 25,000 people in a study from the North West of England ( Types references ). It manifests primarily as congenital bilateral gene ( Types references ). In the remaining cases, the genetic basis is not well-understood, but in tissue from some patients, other mutations in the same gene are involved. Two or more schwannomas develop in spinal and peripheral nerves and are sometimes quite painful; however, vestibular schwannomas do not develop. Schwannomatosis used to be considered a form of NF2 because multiple schwannomas are present in both conditions; however, the clinical picture is different, and the genes involved are distinct. Tumors may be peripheral or central. Peripheral tumorsare common in NF1 and can develop anywhere along the course of peripheral nerves. The tumors are neurofibromas, which develop from nerve sheaths and consist of mixtures of Schwann cells, fibroblasts, neural cells, and mast cells. Most appear during adolescence. Occasionally, they transform to malignant peripheral nerve sheath tumors. There are multiple forms: Cutaneous neurofibromasare soft and fleshy. Subcutaneous neurofibromasare firm and nodular. Nodular plexiform neurofibromasmay involve spinal nerve roots, typically growing through an intervertebral foramen to cause intraspinal and extraspinal masses (dumbbell tumor). The intraspinal part may compress the spinal cord. Diffuse plexiform neurofibromas(subcutaneous nodules or amorphous overgrowth of underlying bone or Schwann cells) can be disfiguring and may cause deficits distal to the neurofibroma. Plexiform neurofibromas can become malignant and they appear to be the most common precursors to malignant peripheral nerve sheath tumors in people with NF1. Schwannomasare derived from Schwann cells, rarely undergo malignant transformation, and can occur in peripheral nerves anywhere in the body. Central tumorshave several forms: Optic gliomas:These tumors are low-grade pilocytic astrocytomas, which may be asymptomatic or may progress enough to compress the optic nerve and cause blindness. They occur in younger children; these tumors can usually be identified by age 5 and rarely develop after age 10. They occur in NF1. Vestibular Schwannoma (acoustic neuromas): Meningiomas : 1.Plotkin SR, Messiaen L, Legius E, et al: Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation.Genet Med24(9):1967-1977, 2022. doi: 10.1016/j.gim.2022.05.007 2.Evans DG, Howard E, Giblin C, et al: Birth incidence and prevalence of tumor-prone syndromes: Estimates from a UK family genetic register service.Am J Med Genet A152A(2):327-332, 2010. doi: 10.1002/ajmg.a.33139 3.Evans DG, Moran A, King A, et al: Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: Higher incidence than previously thought.Otol Neurotol26(1):93-97, 2005. doi: 10.1097/00129492-200501000-00016 4.Evans DG, Huson SM, Donnai D, et al:A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity.J Med Genet29(12):841-846, 1992. doi: 10.1136/jmg.29.12.841 