Abstract
Simple SummaryCentral nervous system involvement (CNS) is a common finding in Neurofibromatosis type 1 (NF1). Beside tumor-related manifestations, NF1 is also characterized by a wide spectrum of CNS alterations with variable impacts on functioning and life quality. Here, we propose an overview of non-oncological neuroradiological findings in NF1, with an insight on pathophysiological and embryological clues for a better understanding of the development of these specific alterations.Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is characterized by several manifestations that pervasively involve central and peripheral nervous system structures. The disorder is due to mutations in the NF1 gene, which encodes for the ubiquitous tumor suppressor protein neurofibromin; neurofibromin is highly expressed in neural crest derived tissues, where it plays a crucial role in regulating cell proliferation, differentiation, and structural organization. This review article aims to provide an overview on NF1 non-neoplastic manifestations of neuroradiological interest, involving both the central nervous system and spine. We also briefly review the most recent MRI functional findings in NF1.
Highlights
Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is a multi-organ autosomal dominant disease with an incidence ranging between 1:2000 and 1:3000 newborns and a prevalence of about 1:4500 [1]
In NF1 patients, the heterozygous pathogenic gene variant is present in every nucleated cell; in case of loss of heterozygosity or when the second wild-type allele is inactivated by a new intra-genic mutation, neurofibromin becomes inactive or lacking within the cell with repercussion on the RAS-MAPK pathway
Ubiquitous, NF1 is highly expressed in neural crest (NC) derived tissues where it has a prominent regulatory activity on neural stem cell proliferation and precursor migration, with a specific effect depending on the target cell type, arising from each segment of the neural tube [7] (Table 1)
Summary
Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is a multi-organ autosomal dominant disease with an incidence ranging between 1:2000 and 1:3000 newborns and a prevalence of about 1:4500 [1]. Coordination disorders with reduced visuo-spatial/motor abilities, comprehension deficit, linguistic impairment, autistic mannerisms and attention deficit/hyperactivity disorder represent the most common cognitive manifestations of NF1 [40,41,42,56] All these findings taken together could probably reflect a delayed or aberrant dendritic pruning depending, at least in part, on NF1 gene mutations; at present, the correlation between impaired function and the involved brain regions is still poorly understood, these preliminary findings suggest a possible role of these in vivo biomarkers for future disease monitoring and treatment response assessment [18]. The variable prevalence and penetrance of these cognitive dysfunctions in NF1 patients plead in favor of the existence of multiple physiopathological mechanisms, which cannot be fully elucidated by morphological and structural neuroimaging approaches alone [44]
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