Effect of Simvastatin on Cognitive Functioning in Children With Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) is a common autosomal-dominant genetic disorder (incidence 1:3000)¹ caused by a mutation in the gene encoding neurofibromin, a protein that activates the hydrolysis of RAS-bound guanosine triphosphate.² Neurofibromatosis type 1 is characterized by various neurocutaneous manifestations, problems in fine and gross motor functioning,³ as well as the frequent occurrence of cognitive disabilities. Children with NF1 have a lower mean IQ (86-94) with particular deficits in visual-spatial skills, nonverbal long-term memory, executive functions, and attention.^4-7 These problems have a large impact on school performance of children with NF1.⁴ It has been suggested that the cognitive and motor deficits in children with NF1 are related to hyperintensities on T2-weighed magnetic resonance imaging of the brain^3,8 that are characterized by high apparent diffusion coefficients (ADC values),⁹ but some studies failed to confirm this relationship.¹⁰