title: Diagnosis, Management, and New Therapeutic Options in Childhood Neurofibromatosis Type 2 and Related Forms.
abstract: Neurofibromatosis type 2 (NF2; MIM # 101000) is an autosomal dominant disorder characterized by the development of vestibular schwannomas (VSs); schwannomas of other cranial, spinal, and cutaneous nerves; cranial and spinal meningiomas or other central nervous system tumors (eg, ependymomas and astrocytomas) or both. Additional features include eye (eg, early onset cataracts, optic nerve sheath meningiomas, retinal or pigment epithelial hamartomas or both, and epithelial retinal membranes) and skin abnormalities (eg, flat dermal [NF2 plaques] or spherical subcutaneous nodular schwannomas or both, and few, atypical café-au-lait spots). Clinically, children with NF2 fall into 2 main groups: (1) congenital NF2 with bilateral VSs detected as early as the first days to months of life, which can be stable or asymptomatic for 1-2 decades and suddenly progress; and (2) severe prepubertal (Wishart type) NF2 with multiple (and rapidly progressive) central nervous system tumors other-than-VS, which usually presents first, years before VSs, both associated with more marked skin and eye involvement (vs the classical mild adult [Gardner type] NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature). Individuals manifesting unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localized to a part of the peripheral nervous system have mosaic or segmental NF2; individuals developing multiple nonVS, nonintradermal cranial, spinal, and peripheral schwannomas (histologically proven) have schwannomatosis (SWNTS). NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin proteins; mosaic or segmental NF2 is because of mosaic phenomena for the NF2 gene, whereas SWNTS is caused by germline and possibly mosaic mutations either in the SMARCB1 gene (SWNTS1; MIM # 162091) or the LZTR1 gene (SWNTS2; MIM # 615670), both falling within the 22q region. Data driven from in vitro and animal studies on the merlin pathway allowed biologically targeted treatment strategies (employing Lapatinib, Erlotinib, Everolimus, Picropodophyllin, OSU.03012, Imatinib, Sorafenib, and Bevacizumab) aimed at multiple tumor shrinkage or regression or both and tumor arrest of progression with functional improvement.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy. Electronic address: m.ruggieri@unict.it.
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Andrea Domenico
authors.initials: AD
authors.lastname: Praticò
authors.affiliation: Genomic Medicine, Manchester Academic Health Science Centre, Institute of Human Development, University of Manchester, Central Manchester NHS Foundation Trust, Manchester, UK; Department of Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Dafydd Gareth
authors.initials: DG
authors.lastname: Evans
mesh_terms: D000818:Animals; D006801:Humans; D016518:Neurofibromatosis 2 / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*