Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype?
Background: Cognitive impairment is the most common neurological manifestation in NF1 and occurs in 30–70% of NF1 cases. The onset and severity of each specific cognitive deficit varies greatly from child to child, with no apparent external causes. The wide variability of phenotype is the most compl...
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doaj-1a52fbb5cf2440e2b589dea5c57df2f92020-11-25T02:02:36ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-05-011110.3389/fneur.2020.00368530250Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype?Maëlle Biotteau0Maëlle Biotteau1Sébastien Déjean2Sandrine Lelong3Stéphanie Iannuzzi4Nathalie Faure-Marie5Pierre Castelnau6Pierre Castelnau7Pierre Castelnau8François Rivier9Valérie Lauwers-Cancès10Eloïse Baudou11Eloïse Baudou12Yves Chaix13Yves Chaix14ToNIC, Toulouse NeuroImaging Center, University of Toulouse, Inserm, UPS, Toulouse, FranceChildren's Hospital, Toulouse-Purpan University Hospital, Toulouse, FranceInstitut de Mathématiques de Toulouse, UMR5219 Université de Toulouse, CNRS UPS, Toulouse, FranceChildren's Hospital, Toulouse-Purpan University Hospital, Toulouse, FranceChildren's Hospital, Toulouse-Purpan University Hospital, Toulouse, FranceChildren's Hospital, Toulouse-Purpan University Hospital, Toulouse, FranceUMR 1253, iBrain, University of Tours, INSERM, Tours, FranceDepartment of Medicine, University of Tours Francois Rabelais, Tours, FrancePediatric Neurology, Clocheville Children's Hospital, Tours University Hospital, Tours, FranceDepartment of Pediatric Neurology and Reference Center for Language Disabilities, CHU Montpellier, PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, FranceEpidemiology Department, Toulouse University Hospital, Toulouse, FranceToNIC, Toulouse NeuroImaging Center, University of Toulouse, Inserm, UPS, Toulouse, FranceChildren's Hospital, Toulouse-Purpan University Hospital, Toulouse, FranceToNIC, Toulouse NeuroImaging Center, University of Toulouse, Inserm, UPS, Toulouse, FranceChildren's Hospital, Toulouse-Purpan University Hospital, Toulouse, FranceBackground: Cognitive impairment is the most common neurological manifestation in NF1 and occurs in 30–70% of NF1 cases. The onset and severity of each specific cognitive deficit varies greatly from child to child, with no apparent external causes. The wide variability of phenotype is the most complex aspect in terms of management and care. Despite multiple research, the mechanism underlying the high heterogeneity in NF1 has not yet been elucidated. While many studies have focused on the effects of specific and precise genetic mutations on the NF1 phenotype, little has been done on the impact of NF1 transmission (sporadic vs. familial cases). We used a complete neuropsychological evaluation designed to assess five large cognitive areas: general cognitive functions (WISC-IV and EVIP); reading skills (“L'Alouette,” ODEDYS-2 and Lobrot French reading tests); phonological process (ODEDYS-2 test); visual perceptual skills (JLO, Thurstone and Corsi block tests) and attention (CPT-II), as well as psychosocial adjustments (CBCL) to explore the impact of NF1 transmission on cognitive disease manifestation in 96 children affected by NF1 [55 sporadic cases (29♀, 26♂); 41 familial cases (24♀, 17♂)].Results: Familial and Sporadic form of NF1 only differ in IQ expression. The families' socioeconomic status (SES) impacts IQ performance but not differently between sporadic and familial variants. However, SES is lower in familial variants than in the sporadic variant of NF1. No other cognitive differences emerge between sporadic and familial NF1.Conclusions: Inheritance in NF1 failed to explain the phenotype variability in its entirety. IQ differences between groups seems in part linked to the environment where the child grows up. Children with NF1, and especially those that have early diagnoses (most often in inherited cases), must obtain careful monitoring from their early childhood, at home to strengthen investment in education and in school to early detect emerging academic problems and to quickly place them into care.Trial Registration: IDRCB, IDRCB2008-A01444-51. Registered 19 January 2009.https://www.frontiersin.org/article/10.3389/fneur.2020.00368/fullNF1childcognitive profilesporadicfamilialhereditary |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maëlle Biotteau Maëlle Biotteau Sébastien Déjean Sandrine Lelong Stéphanie Iannuzzi Nathalie Faure-Marie Pierre Castelnau Pierre Castelnau Pierre Castelnau François Rivier Valérie Lauwers-Cancès Eloïse Baudou Eloïse Baudou Yves Chaix Yves Chaix |
spellingShingle |
Maëlle Biotteau Maëlle Biotteau Sébastien Déjean Sandrine Lelong Stéphanie Iannuzzi Nathalie Faure-Marie Pierre Castelnau Pierre Castelnau Pierre Castelnau François Rivier Valérie Lauwers-Cancès Eloïse Baudou Eloïse Baudou Yves Chaix Yves Chaix Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype? Frontiers in Neurology NF1 child cognitive profile sporadic familial hereditary |
author_facet |
Maëlle Biotteau Maëlle Biotteau Sébastien Déjean Sandrine Lelong Stéphanie Iannuzzi Nathalie Faure-Marie Pierre Castelnau Pierre Castelnau Pierre Castelnau François Rivier Valérie Lauwers-Cancès Eloïse Baudou Eloïse Baudou Yves Chaix Yves Chaix |
author_sort |
Maëlle Biotteau |
title |
Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype? |
title_short |
Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype? |
title_full |
Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype? |
title_fullStr |
Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype? |
title_full_unstemmed |
Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype? |
title_sort |
sporadic and familial variants in nf1: an explanation of the wide variability in neurocognitive phenotype? |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2020-05-01 |
description |
Background: Cognitive impairment is the most common neurological manifestation in NF1 and occurs in 30–70% of NF1 cases. The onset and severity of each specific cognitive deficit varies greatly from child to child, with no apparent external causes. The wide variability of phenotype is the most complex aspect in terms of management and care. Despite multiple research, the mechanism underlying the high heterogeneity in NF1 has not yet been elucidated. While many studies have focused on the effects of specific and precise genetic mutations on the NF1 phenotype, little has been done on the impact of NF1 transmission (sporadic vs. familial cases). We used a complete neuropsychological evaluation designed to assess five large cognitive areas: general cognitive functions (WISC-IV and EVIP); reading skills (“L'Alouette,” ODEDYS-2 and Lobrot French reading tests); phonological process (ODEDYS-2 test); visual perceptual skills (JLO, Thurstone and Corsi block tests) and attention (CPT-II), as well as psychosocial adjustments (CBCL) to explore the impact of NF1 transmission on cognitive disease manifestation in 96 children affected by NF1 [55 sporadic cases (29♀, 26♂); 41 familial cases (24♀, 17♂)].Results: Familial and Sporadic form of NF1 only differ in IQ expression. The families' socioeconomic status (SES) impacts IQ performance but not differently between sporadic and familial variants. However, SES is lower in familial variants than in the sporadic variant of NF1. No other cognitive differences emerge between sporadic and familial NF1.Conclusions: Inheritance in NF1 failed to explain the phenotype variability in its entirety. IQ differences between groups seems in part linked to the environment where the child grows up. Children with NF1, and especially those that have early diagnoses (most often in inherited cases), must obtain careful monitoring from their early childhood, at home to strengthen investment in education and in school to early detect emerging academic problems and to quickly place them into care.Trial Registration: IDRCB, IDRCB2008-A01444-51. Registered 19 January 2009. |
topic |
NF1 child cognitive profile sporadic familial hereditary |
url |
https://www.frontiersin.org/article/10.3389/fneur.2020.00368/full |
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