Examining the frontal subcortical brain vulnerability hypothesis in children with neurofibromatosis type 1: Are T2-weighted hyperintensities related to executive dysfunction?

Roy, Arnaud; Barbarot, S.; Charbonnier, Valérie; Gayet-Delacroix, M.; Stalder, J.‐F.; Roulin, Jean-Luc; Gall, Didier Le

doi:10.1037/neu0000151

Cited by 35 publications

(40 citation statements)

References 47 publications

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“…The latter would, however, be in conflict with a slight majority of studies that concluded that T2Hs associated with NF1 have a negative impact cognitive ability. [39][40][41][42] However, if the presence of T2Hs shows a high concordance within 11 NF1 MZ twin pairs as previously suggested, 12 it is debatable whether presence of T2Hs should be considered a nongenetic factor in the first place. Lastly, while allelic imbalance was observed in neurons derived from induced pluripotent stem cells of NF1 individuals and correlated with dopamine signaling, 19 our results collectively indicate that allelic imbalance is unlikely to add significantly to the variability of the cognitive NF1 phenotype.…”

Section: Discussionmentioning

confidence: 94%

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1

Ottenhoff

Rietman

Mous

et al. 2020

Genetics in Medicine

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Purpose: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder associated with cognitive deficits. The NF1 cognitive phenotype is generally considered to be highly variable, possibly due to the observed T2-weighted hyperintensities, loss of heterozygosity, NF1-specific genetic modifiers, or allelic imbalance. Methods: We investigated cognitive variability and assessed the contribution of genetic factors by performing a retrospective cohort study and a monozygotic twin case series. We included data of 497 children with genetically confirmed NF1 and an IQ assessment, including 12 monozygotic twin and 17 sibling sets. Results: Individuals carrying an NF1 chromosomal microdeletion showed significant lower full-scale IQ (FSIQ) scores than individuals carrying intragenic pathogenic NF1 variants. For the intragenic subgroup, the variability in cognitive ability and the correlation of IQ between monozygotic NF1 twin pairs or between NF1 siblings is similar to the general population. Conclusions: The variance and heritability of IQ in individuals with NF1 are similar to that of the general population, and hence mostly driven by genetic background differences. The only factor that significantly attenuates IQ in NF1 individuals is the NF1 chromosomal microdeletion genotype. Implications for clinical management are that individuals with intragenic NF1 variants that score <1.5-2 SD below the mean of the NF1 population should be screened for additional causes of cognitive disability.

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Section: Discussionmentioning

confidence: 94%

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1

Ottenhoff

Rietman

Mous

et al. 2020

Genetics in Medicine

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“…Two articles reported additional interesting results related to T2H. Roy et al ( 34 ) found that the presence, number, size, or location of T2H lesions did not affect executive dysfunction in NF1 children. On the other hand, Piscitelli et al ( 35 ) found that patients with T2H in the cerebellum showed a lower IQ than patients without T2H in that brain location, possibly because of impaired visuospatial ability and language.…”

Section: Resultsmentioning

confidence: 99%

Cognitive and Behavioral Disorders in Children with Neurofibromatosis Type 1

et al. 2017

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AimThe last systematic review of research on the behavior of children with neurofibromatosis type 1 (NF1) was in 2012. Since then, several important findings have been published. Therefore, the study aim was to synthesize recent relevant work related to this issue.MethodWe conducted a systematic review of the literature. Relevant articles were identified using the electronic databases PubMed, PsycINFO, and Scopus and a manual search of references lists. Thirty of 156 articles identified met the inclusion criteria. A quality evaluation of the articles was performed and the information was synthesized using a narrative approach.ResultsCompared with controls, children and adolescents with NF1 present significant alterations in language, reading, visuospatial skills, motor function, executive function, attention, behavior, emotion, and social skills. The prevalence of attention-deficit/hyperactivity disorder (ADHD) is important and can affect cognition and executive function variables. A high prevalence of autistic traits and autistic spectrum disorder were reported. The benefits of using statins to treat cognitive deficits are unclear. However, children with NF1 and ADHD seem to benefit from methylphenidate treatment. The presence of hyperintensities in brain magnetic resonance imaging data seem to be related to poor cognitive performance. Analysis of these lesions could help to predict cognitive alterations in children with NF1.InterpretationThere has been important progress to evaluate cognitive characteristics of children with NF1 and to determine the physiological mechanisms of the concomitant disorders. However, discrepancies in relation to intelligence, learning disabilities, attention deficits, and treatment remain. Further investigations on this topic are recommended.

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“…Subjects with cerebellar UBOs (31 out of 49 NF1 children in the study) presented worse scores on verbal IQ, full-scale IQ and visuospatial tests (reasoning and memory) than subjects without cerebellar hyperintensities (18 out of 49 NF1 children in the study). However, Roy et al (33) showed no relationship between executive functions, evaluated with a test or a questionnaire, and the presence, number or location of T2-hyperintensities ( Table 2).…”

Section: Post 2010 Studies Morphologic Neuroimaging and The Relationsmentioning

confidence: 99%

Can the Cognitive Phenotype in Neurofibromatosis Type 1 (NF1) Be Explained by Neuroimaging? A Review

et al. 2020

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Examining the frontal subcortical brain vulnerability hypothesis in children with neurofibromatosis type 1: Are T2-weighted hyperintensities related to executive dysfunction?

Cited by 35 publications

References 47 publications

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1

Cognitive and Behavioral Disorders in Children with Neurofibromatosis Type 1

Can the Cognitive Phenotype in Neurofibromatosis Type 1 (NF1) Be Explained by Neuroimaging? A Review

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