Longitudinal Investigation of Early Motor Development in Neurofibromatosis Type 1.

OBJECTIVE: Research indicates that children with neurofibromatosis type 1 (NF1) have weaknesses in fine and gross motor development in early childhood; however, little is known about the stability and developmental trajectory of motor functioning. We investigated (1) whether motor difficulties are evident and stable in the preschool period in children with NF1 and (2) whether there are particular patterns of motor development in this population. METHODS: Participants with NF1 and a control group of unaffected siblings were enrolled at ages 3-8 years and were assessed yearly. Motor functioning was assessed longitudinally using the Scales of Independent Behavior-Revised Motor Scale and the Differential Ability Scales-II Copying subtest. Wilcoxon sign tests were used to compare motor functioning at 3 or 4 years to 5 or 6 years old for children with NF1 seen during both time periods (N = 27). Linear mixed model growth curve analyses were used to compare trajectories for both children with NF1 (N = 62) and unaffected siblings (N = 37). RESULTS: Children with NF1 made relative gains in raw scores, but not standard scores, across measures. Growth curve analyses revealed a significant effect of NF1 status on gross motor, fine motor, and copying scores, as well as an age by NF1 status effect on fine and gross motor scores. CONCLUSIONS: Motor difficulties are evident early in life in children with NF1. Though children with NF1 clearly acquire motor skills over time, they continue to fall behind unaffected siblings, with the gap potentially widening over time. Further implications are discussed.

Recommendations for Measurement of Attention Outcomes in Preschoolers With Neurofibromatosis.

Children with neurofibromatosis type 1 (NF1) are at increased risk for attention problems. While most research has been conducted with school-aged cohorts, preschool-aged children offer a novel developmental window for clinical studies, with the promise that treatments implemented earlier in the developmental trajectory may most effectively modify risk for later difficulties. Designing research studies around the youngest children with NF1 can result in intervention earlier in the developmental cascade associated with NF1 gene abnormalities. Furthermore, clinical trials for medications targeting physical and psychological aspects of NF1 often include individuals spanning a wide age range, including preschool-aged children. In a prior report, the REiNS Neurocognitive Subcommittee made recommendations regarding performance-based and observer-rated measures of attention for use in clinical trials and highlighted the need for separate consideration of assessment methods for young children. The observer-rated Attention-Deficit/Hyperactivity Disorder Rating Scale-Preschool version is recommended as a primary outcome measure. The NIH Toolbox Flanker, Dimensional Change Card Sort, and List Sort Working Memory tasks and Digits Forward from the Differential Ability Scales-2nd Edition (performance-based measures) are recommended as secondary outcome measures. Specific methodologic recommendations for inclusion of preschoolers in clinical trials research are also offered.

Relations between fine motor skill and parental report of attention in young children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders presenting in approximately 1 in 3,500 live births. NF1 is a highly variable condition with a large number of complications. A common complication is neuropsychological problems, including developmental delays and learning difficulties that affect as many as 60% of patients. Research has suggested that school-aged children with NF1 often have poorer fine motor skills and are at greater risk for attention difficulties than the general population. Thirty-eight children with NF1 and 23 unaffected children between the ages of 4 and 6 years, who are enrolled in a study of early development in NF1, were included in the present study. Varying levels of fine motor functioning were examined (simple to complex fine motor tasks). For children with NF1, significant difficulties were demonstrated on lab-based mid-level and complex fine motor tasks, even after controlling for nonverbal reasoning abilities, but not on simple fine motor tasks. Parental report also indicated difficulties in everyday adaptive fine motor functioning. No significant correlations were found between complex fine motor ability and attention difficulties. This study provides much needed descriptive data on the early emergence of fine motor difficulties and attention difficulties in young children with NF1.

Cognitive and psychosocial phenotype of young children with neurofibromatosis-1.

Children with neurofibromatosis-1 (NF1), a neurodevelopmental disorder resulting from a mutation of the NF1 gene (17q11.2), often have difficulties with learning and attention, but there is little research in the early childhood years. In this study, the cognitive and psychosocial functioning of 40 young children with NF1 (ages 3 through 6) was examined and compared both to normative data and to a contrast group comprised of unaffected siblings and community members matched for age and socio-economic status (n = 37). Children with NF1 showed significantly weaker cognitive abilities across all domains and for the vast majority of subtests. Consistent with research in older children, a variety of patterns of intra-individual strength and weakness were present for young children with NF1. Few significant group differences in psychosocial functioning were observed, but the children with NF1 showed significantly greater functional communication problems than did the unaffected group. Overall, the results indicate that in participant groups matched for age and socioeconomic status, cognitive vulnerabilities are evident for close to half of young children with NF1, with some relations to psychosocial functioning, particularly functional communication, attention problems and social skills.

Adaptive behavior in young children with neurofibromatosis type 1.

Neurofibromatosis-1 is the most common single gene disorder affecting 1 in 3000. In children, it is associated not only with physical features but also with attention and learning problems. Research has identified a downward shift in intellectual functioning as well, but to date, there are no published studies about the everyday adaptive behavior of children with NF1. In this study, parental reports of adaptive behavior of 61 children with NF1 ages 3 through 8 were compared to an unaffected contrast group (n = 55) that comprised siblings and community members. Significant group differences in adaptive skills were evident and were largely related to group differences in intellectual functioning. In a subsample of children with average-range intellectual functioning, group differences in parent-reported motor skills were apparent even after controlling statistically for group differences in intellectual functioning. The implications of the findings for the care of children with NF1 are discussed.