Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype?

Biotteau, Maëlle; Déjean, Sébastien; Lelong, Sandrine; Iannuzzi, Stéphanie; Faure-Marie, Nathalie; Castelnau, Pierre; Rivier, François; Lauwers‐Cancès, Valérie; Baudou, E.; Chaix, Yves

doi:10.3389/fneur.2020.00368

Cited by 21 publications

(6 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two recent studies have also examined the cognitive and academic differences in children with inherited versus de novo NF1 mutations. One study suggested that lower IQ in the inherited NF1 group was largely mediated by lower socioeconomic status in families with NF1 (Biotteau et al, 2020). Conversely another study found that having a parent with NF1 was related to lower academic and cognitive skills despite adjusting for socio-economic status (Geoffray et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Early Developmental Trajectories in Infants With Neurofibromatosis 1

et al. 2022

View full text Add to dashboard Cite

ObjectiveTo examine the trajectories of cognitive, motor and behavioural development in infants with NF1 compared to infants without a family history of neurodevelopmental difficulties.Study designInfants with NF1 and low-risk controls were recruited from 5 months of age and followed longitudinally. Data from standardised tests was gathered at 5, 10 and 14 months and developmental trajectories of motor, language, behaviour, sleep, social development and parent–infant interaction were examined. Linear mixed modelling was used to estimate group differences in cognitive and behavioural measures over time.ResultsNo group differences were observed on Mullen Scale of Early Learning, overall adaptive functioning, temperament or behavioural measures. There were no group differences observed on measures of social communication or parent–infant interaction. Over the course of development, the NF1 group slept less and took more time to settle to sleep as compared to the control group. Maternal education was significantly associated with cognitive and behavioural developmental outcomes in both groups.ConclusionCognitive, social and behavioural impairments are a cause of significant functional morbidity in children with NF1. This report is the first study to investigate the trajectories of cognitive, motor and behavioural development in infancy in NF1. Our results demonstrate that overall cognitive and behavioural developmental trajectories of the NF1 group in the infancy period are similar to controls. Given previous reports of delayed development in the NF1 cohort by 40 months, early clinical interventions strategies to promote sleep hygiene may be beneficial to optimise developmental outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Early Developmental Trajectories in Infants With Neurofibromatosis 1

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Prognosis is generally poor, with a high risk of relapse following multimodality therapy in early disease, low response rates of cytotoxic chemotherapy in advanced disease, and propensity for rapid disease progression and high mortality. It has been reported that about 50% of NF1 cases are due to de novo mutations 41 . Our patient had not a family history however, presented multiple cafe au lait spots and subcutaneous neurofibromas (Table 4 ), had three relapses during the treatment (pulmonary, axillary and extrapleural relapses) and died of disease progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing

Alba-Pavón

Alaña

Gutiérrez-Jimeno

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans´ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.

show abstract

“…Third, we were unable to examine the role of genotype and transmission pattern as these variables were similarly underreported. Recent studies have noted that these variables may influence cognitive deficits in NF1 (e.g., Biotteau et al, 2020;Ottenhoff et al, 2020). While few genotype-phenotype correlations have been demonstrated in NF1 (Bettegowda et al, 2021), future studies should examine the contribution of genotype and transmission pattern to cognitive variability in NF1.…”

Section: Limitationsmentioning

confidence: 99%

A systematic review and meta‐analysis of intellectual, neuropsychological, and psychoeducational functioning in neurofibromatosis type 1

Crow

Janssen

Marshall

et al. 2022

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Neurofibromatosis Type 1 (NF1) is a common genetic disorder frequently associated with cognitive deficits. Despite cognitive deficits being a key feature of NF1, the profile of such impairments in NF1 has been shown to be heterogeneous. Thus, we sought to quantitatively synthesize the extant literature on cognitive functioning in NF1. A random-effects meta-analysis of cross-sectional studies was carried out comparing cognitive functioning of patients with NF1 to typically developing or unaffected sibling comparison subjects of all ages. Analyses included 50 articles (Total N NF1 = 1,522; M Age = 15.70 years, range = 0.52-69.60), yielding 460 effect sizes. Overall moderate deficits were observed [g = À0.64, 95% CI = (À0.69, À0.60)] wherein impairments differed at the level of cognitive domain. Deficits ranged from large [general intelligence: g = À0.95, 95% CI = (À1.12, À0.79)] to small [emotion: g = À0.37, 95% CI = (À0.63, À0.11)]. Moderation analyses revealed nonsignificant contributions of age, sex, educational attainment, and parental level of education to outcomes. These results illustrate that cognitive impairments are diffuse and salient across the lifespan in NF1. Taken together, these results further demonstrate efforts should be made to evaluate and address cognitive morbidity in patients with NF1 in conjunction with existing best practices.

show abstract

Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype?

Cited by 21 publications

References 108 publications

Early Developmental Trajectories in Infants With Neurofibromatosis 1

Early Developmental Trajectories in Infants With Neurofibromatosis 1

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing

A systematic review and meta‐analysis of intellectual, neuropsychological, and psychoeducational functioning in neurofibromatosis type 1

Contact Info

Product

Resources

About