Profiling the Word Reading Abilities of School-Age Children with Neurofibromatosis Type 1.

OBJECTIVE: Reading difficulties are one of the most significant challenges for children with neurofibromatosis type 1 (NF1). The aims of this study were to identify and categorize the types of reading impairments experienced by children with NF1 and to establish predictors of poor reading in this population. METHOD: Children aged 7-12 years with NF1 (n = 60) were compared with typically developing children (n = 36). Poor word readers with NF1 were classified according to impairment type (i.e., phonological, surface, mixed), and their reading subskills were compared. A hierarchical multiple regression was conducted to identify predictors of word reading. RESULTS: Compared to controls, children with NF1 demonstrated significantly poorer literacy abilities. Of the 49 children with NF1 classified as poor readers, 20 (41%) were classified with phonological dyslexia, 24 (49%) with mixed dyslexia, and 5 (10%) fell outside classification categories. Children with mixed dyslexia displayed the most severe reading impairments. Stronger working memory, better receptive language, and fewer inattentive behaviors predicted better word reading skills. CONCLUSIONS: The majority of children with NF1 experience deficits in key reading skills which are essential for them to become successful readers. Weaknesses in working memory, receptive language, and attention are associated with reading difficulties in children with NF1.

Preliteracy impairments in children with neurofibromatosis type 1.

AIM: This cross-sectional study aimed to examine the preliteracy abilities of young children with neurofibromatosis type 1 (NF1) and to identify which of these abilities best predicted conventional literacy (spelling). METHOD: Forty-two children with NF1 (23 males, 19 females; mean age [SD] 5y 6mo [6mo]) were compared with 32 unaffected children (15 males, 17 females; mean age [SD] 5y 4mo [6mo]). All children completed a comprehensive cognitive assessment including measures of phonological processing (phonological awareness, phonological memory, rapid automatic naming) and letter-sound knowledge. RESULTS: Children with NF1 performed significantly poorer than the comparison group across all cognitive and preliteracy domains, with specific weaknesses evident in phonological awareness (F1,68 =14.13, p<0.001, partial η2 =0.17), phonological memory (F1,68 =13.87, p<0.001, partial η2 =0.17), and letter-sound knowledge (F1,71 =5.65, p=0.020, partial η2 =0.07). Within the group with NF1 group, over a third of children demonstrated impairment in at least one phonological processing domain and the risk of phonological impairment was 5.60 times that of unaffected children. Children's letter-sound knowledge was the strongest predictor of conventional literacy (spelling). INTERPRETATION: This study establishes that preliteracy deficits are present and detectable in young children with NF1. As a result of the high incidence of preliteracy impairment, we recommend screening phonological awareness and letter-sound knowledge to identify risk of future learning disorders. WHAT THIS PAPER ADDS: Young children with neurofibromatosis type 1 are at elevated risk of preliteracy deficits. The most affected domains are phonological awareness and phonological memory. Letter-sound knowledge is the strongest predictor of conventional literacy (spelling).

Phonics Training Improves Reading in Children with Neurofibromatosis Type 1: A Prospective Intervention Trial.

OBJECTIVE: To examine the efficacy of a phonics-training program in children with neurofibromatosis type 1 (NF1) and reading difficulties. STUDY DESIGN: Thirty children (7-12 years of age) with NF1 completed a double-baseline, 24-week intervention trial. Literacy outcome measures were assessed at 4 time points: (1) at baseline; (2) after an 8-week no-treatment period; (3) immediately post-treatment; and (4) at follow-up 8 weeks post-treatment. Repeated-measures ANOVA were conducted to examine change over time for all outcome measures, and significant main effects were explored with planned comparisons. Predictors of treatment effects were examined by linear regressions. RESULTS: Ninety percent of participants completed the intervention. Intervention-specific improvements were observed across a range of literacy outcomes, including reading accuracy (nonword reading, Cohen d = 1.10; regular-word reading, Cohen d = 0.32), letter-sound knowledge (Cohen d = 0.80), blending (Cohen d = 0.88), repetition of nonsense words (Cohen d = 0.94), phonemic decoding fluency (Cohen d = 0.55), and reading comprehension (Cohen d = 0.31). Improvements were maintained 8 weeks post-treatment. Age (P = .03) and working memory (P = .02) significantly influenced efficacy, with greatest improvements observed in older children with stronger verbal working memory capacity. CONCLUSIONS: Home-based, computerized reading intervention was effective in improving the reading and reading-related abilities of children with NF1 and reading difficulty. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12611000779976.

Developmental trajectories of young children with neurofibromatosis type 1: a longitudinal study from 21 to 40 months of age.

OBJECTIVE: To establish the developmental trajectory of young children with neurofibromatosis type 1 (NF1) during the first 4 years of life. STUDY DESIGN: In this longitudinal study, 39 children with NF1 and 39 controls were assessed with the Bayley Scales of Infant Development, Second Edition at 21 (time point 1, or T1) and 30 months (T2) of age, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition at 40 months (T3). Language was also assessed at T2 and T3. Parents rated their child's productive vocabulary at T1 and T2, and behavior at each time point. Linear mixed models were performed to examine cognitive development and behavior over time. Linear regressions were conducted to determine whether mental development and productive vocabulary at T1 or T2 predicted intellectual and language outcomes at T3. RESULTS: Over time, the NF1 group had significantly lower cognitive scores than controls. Parent ratings indicated no group differences in behavior at each time point. Earlier mental function significantly predicted later general intelligence. Earlier productive vocabulary was a significant predictor of later language skills. CONCLUSIONS: There are consistent differences over time in cognitive performance between children with NF1 and unaffected peers during the early childhood period. Earlier mental function and productive vocabulary are significant predictors of subsequent general intelligence and performance on language measures in NF1. This provides an opportunity for early identification and treatment for young children with NF1 who may show signs of impairments in these developmental domains.

Cognitive features that distinguish preschool-age children with neurofibromatosis type 1 from their peers: a matched case-control study.

OBJECTIVE: To examine the cognitive functioning of 40-month-old children with neurofibromatosis type 1 (NF1). STUDY DESIGN: In this case-control study, 43 children with NF1 and 43 comparison children (matched by age, sex, and maternal years of education) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Language, visual perception, preliteracy, and executive functioning were also examined. Parents completed questionnaires about their child's behavior. Group differences were examined using the paired-samples t test or the related Wilcoxon signed rank test. Conditional logistic regression was conducted to identify which cognitive variables predicted group membership (ie, NF1 or control). RESULTS: The NF1 group had significantly poorer general intelligence than matched comparisons. Preschool-age children with NF1 had significantly poorer language, visual perception, response inhibition, and preliteracy skills than comparison children. The Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Object Assembly and Information subtests were significant predictors of group membership. Parent ratings indicated no group differences in behavior. CONCLUSIONS: After accounting for potentially confounding variables of age, sex, and maternal years of education, young children with NF1 have significantly poorer intellectual functioning, expressive language, and visual perception. These cognitive features that distinguish young children with NF1 from healthy peers can be detected in the preschool age group and are likely to impact on learning and performance during early school years. These areas should be targeted for intervention to maximize the developmental outcomes of young children with NF1.

Does attention-deficit-hyperactivity disorder exacerbate executive dysfunction in children with neurofibromatosis type 1?

AIM: Although approximately 40% of children with neurofibromatosis type 1 (NF1) meet diagnostic criteria for attention-deficit-hyperactivity disorder (ADHD), the impact of ADHD on the executive functioning of children with NF1 is not understood. We investigated whether spatial working memory and response inhibition are impaired in children with NF1 without a diagnosis of ADHD and whether executive deficits are exacerbated in children with a comorbid diagnosis. METHOD: Forty-nine children aged 7 to 15 years with NF1 only (31 males, 18 females; mean age 11y, SD 2y 4mo) or 35 with NF1 and ADHD (18 males, 17 females; mean age 10y 8mo, SD 2y 4mo) and 30 typically developing comparison children (16 males, 14 females; mean age 10y, SD 2y 8mo) were compared on measures of spatial working memory and response inhibition. Group differences in IQ and visuospatial ability were controlled for as required. RESULTS: Compared with typically developing children, children with NF1 with or without comorbid ADHD demonstrated significant impairment of both spatial working memory (both p<0.004) and inhibitory control (both p<0.010). There were, however, no differences between the two NF1 groups in spatial working memory (p=0.91) or response inhibition (p=0.78). INTERPRETATION: Executive dysfunction occurs with the same severity in children with NF1, whether or not they have a comorbid diagnosis of ADHD, suggesting that executive impairments are not unique contributors to ADHD symptomatology in NF1. The findings are discussed within the context of recent evidence in Nf1 optic glioma (OPG) mice, in which a mechanistic connection between NF1 gene expression, executive system failure, and dopaminergic pathway integrity has been established.