The behavior and sleep patterns of 64 children (mean age 10 years 7 months) with neurofibromatosis type 1 (NF1) were determined by mail and telephone questionnaire in a study at Park Hospital, University of Oxford, UK. Compared to the general population, increased numbers of children with NF1 had scores in the borderline and abnormal range for peer problems (p<0.001), hyperactivity (p<0.001), emotional symptoms (p<0.001), and conduct disorders (p<0.05). Parasomnias (sleepwalking and sleep terrors) were more frequent in the NF1 patients (p<0.05), and those with frequent sleep disturbance had a higher incidence of conduct, hyperactivity, emotional, and total behavioral disorders (p<0.05 or 0.01). [1]

COMMENT. NF1 is associated with an increased prevalence of behavioral and sleep problems, including attention deficit hyperactivity disorder.

Cognitive impairments and specific learning disabilities occur in 30-65% of patients with NF1, and the association is reviewed by Ward BA and Gutmann DH [2]. These authors cite several studies showing a correlation between unidentified bright objects (T2 hyperintensities) in the brain MRI and cognitive dysfunction, but the observation is controversial and not universal. The role of neurofibromin, the NF1 gene product, in learning is discussed in relation to laboratory and genetic studies in Nf1+1-mice. The increased RAS proto-oncogene activity in these mice is responsible for a spatial learning impairment that is related to g-aminobutyric acid-mediated inhibition. Active RAS, as a result of reduced neurofibromin, leads to tumor formation in NF1. Experimental therapies in trial phase, such as farnesyl transferase inhibitors that decrease RAS levels, are intended to decrease tumor size and these may lead to a reversal of the learning disability. For further articles on NF1 and learning disabilities, see Progress in Pediatric Neurology 111, PNB Publishers, 1997;pp291-294, 441.