Academic Impairment is the Most Frequent Complication of Neurofibromatosis Type-1 (NF1) in Children

Coudé, F. X.; Mignot, Claire; Lyonnet, Stanislas; Münnich, Arnold

doi:10.1007/s10519-005-9040-9

Cited by 38 publications

(34 citation statements)

References 21 publications

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“…To determine whether sex influences the outcome of murine optic glioma, we leveraged an Nf1 GEM strain that develops optic nerve/chiasmal gliomas ( Nf1 -CKO) 14,15 . While optic nerve volumes were indistinguishable between male and female Nf1 -CKO mice (Fig 2A), only female Nf1 -CKO mice exhibited reduced visual acuity on VOS testing (Fig 2B).…”

Section: Resultsmentioning

confidence: 99%

Sex Is a major determinant of neuronal dysfunction in neurofibromatosis type 1

Diggs-Andrews

Brown

Gianino

et al. 2014

Annals of Neurology

126

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Objective Children with Neurofibromatosis-1 (NF1) are at risk for developing numerous nervous system abnormalities, including cognitive problems and brain tumors (optic pathway glioma). Currently, there are few prognostic factors that predict clinical manifestations or outcomes in patients, even in families with an identical NF1 gene mutation. In this study, we leveraged Nf1 genetically-engineered mice (GEM) to define the potential role of sex as a clinically-relevant modifier of NF1-associated neuronal dysfunction. Methods De-identified clinical data were analyzed to determine the impact of sex on optic glioma-associated visual decline in children with NF1. In addition, Nf1 GEM were employed as experimental platforms to investigate sexually dimorphic differences in learning/memory, visual acuity, retinal ganglion cell (RGC) death, and Nf1 protein (neurofibromin)-regulated signaling pathway function (RAS activity, cyclic AMP and dopamine levels). Results Female patients with NF1-associated optic glioma were twice as likely to undergo brain MRI for visual symptoms and three times more likely to require treatment for visual decline than their male counterparts. As such, only female Nf1 GEM exhibited a decrement in optic glioma-associated visual acuity, shorter RGC axons, and attenuated cAMP levels. In contrast, only male Nf1 GEM showed spatial learning/memory deficits, increased RAS activity, and reduced dopamine levels. Interpretation Collectively, these observations establish sex as a major prognostic factor underlying neuronal dysfunction in NF1, and suggest that sex should be considered when interpreting future preclinical and clinical study results.

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Section: Resultsmentioning

confidence: 99%

Sex Is a major determinant of neuronal dysfunction in neurofibromatosis type 1

Diggs-Andrews

Brown

Gianino

et al. 2014

Annals of Neurology

126

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“…[2][3][4][5][6][7][8] Previous studies have shown that the most common psychoeducational problems include visual-perceptual-motor delay and spelling and arithmetic disabilities. 4,9 There is also an increased prevalence of Attention deficit disorder and attention deficit hyperactive disorder in this population. [10][11][12][13] In addition to these impairments, children with neurofibromatosis type 1 frequently demonstrate developmental delays.…”

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confidence: 99%

Longitudinal Analysis of Developmental Delays in Children With Neurofibromatosis Type 1

et al. 2012

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Children with neurofibromatosis type 1 exhibit a variety of developmental delays. However, there is little information about the progression of these deficits over the course of development. Using the Parents' Evaluation of Developmental Status measurement tool, we assessed 124 infants (0-2 years of age), preschool-age children (3-5 years of age), and school-age children (6-8 years of age) with neurofibromatosis type 1 to define the natural history of delays. School-age children exhibited significantly more areas of delay than infants or preschool-age children. Delays in math, reading, gross motor, fine motor, and self-help development were observed more frequently in older than younger children. Finally, analysis of 43 subjects for whom longitudinal assessments were available revealed that children often migrated between delayed and nondelayed groups in all areas except gross motor development. Based on these findings, we advocate early developmental screening and intervention for this at-risk pediatric population, especially in the area of gross motor function.

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“…3,4 Visual-spatial deficits and difficulties with complex motor tasks are commonly seen in individuals with neurofibromatosis type 1 and can be considered hallmark features of neuropsychological impairment in children with neurofibromatosis type 1. [4][5][6][7] At the cellular level, understanding of the underlying genetic defect in neurofibromatosis type 1 has become central to understanding the varied clinical spectrum of disease. The protein product of the neurofibromatosis type 1 gene, neurofibromin, is expressed in many tissues, including neurons, oligodendrocytes, and other nonneural cell types.…”

mentioning

confidence: 99%

Pilot Study of a Novel Computerized Task to Assess Spatial Learning in Children and Adolescents With Neurofibromatosis Type 1

et al. 2010

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Difficulties with visual-spatial learning are frequently observed and often considered to be the hallmark of neurocognitive impairment in neurofibromatosis type 1. The computerized Arena Maze is a virtual environment task that has been developed as a human paradigm to the Morris Water Maze, which is used to evaluate spatial learning in animal models. The authors evaluated this task as a measure of spatial learning in children with neurofibromatosis type 1 compared with their unaffected siblings. Affected children were able to learn the task and navigate the virtual environment; however, they performed more poorly on standard measures of spatial learning and spatial working memory than their siblings. The group with neurofibromatosis type 1 demonstrated decreased proficiency in earlier target trials and had more difficulty in remembering target location. This study demonstrates the potential utility of a novel virtual task to assess spatial learning deficits in children with neurofibromatosis type 1.

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Academic Impairment is the Most Frequent Complication of Neurofibromatosis Type-1 (NF1) in Children

Cited by 38 publications

References 21 publications

Sex Is a major determinant of neuronal dysfunction in neurofibromatosis type 1

Sex Is a major determinant of neuronal dysfunction in neurofibromatosis type 1

Longitudinal Analysis of Developmental Delays in Children With Neurofibromatosis Type 1

Pilot Study of a Novel Computerized Task to Assess Spatial Learning in Children and Adolescents With Neurofibromatosis Type 1

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