Neurological comorbidity in children with neurofibromatosis type 1

Abstract

Background: The aim of this study was to determine the frequency of central nervous system comorbidities in children with neurofibromatosis type 1 (NF1).

Methods: We performed a nationwide survey to investigate neurological comorbidities in 3-15-year-old children with NF1 in Japan by sending questionnaires to pediatricians and pediatric neurologists. A secondary questionnaire was sent to the parents of identified NF1 patients to assess neurological comorbidities including headache, attention deficit-hyperactivity disorder (ADHD) Rating Scale (RS), and the Social Responsiveness Scale 2.

Results: The primary survey identified 760 NF1 patients, and the parents of 565 patients were sent the secondary questionnaire. The parental response rate was 25.7% (145; 63 girls, 81 boys, one unspecified). Among the patients, 42.9% (55/128; 35 girls, 20 boys) were reported to exhibit intellectual problems. On the ADHD-RS, 40.2% (47/117) of NF1 patients aged 6-15 had ADHD (RS score >93rd percentile), with a rate of 47.7% in boys and 30.8% in girls. Furthermore, 20.2% of patients had suspected autism spectrum disorder (29/143; 10 girls, 19 boys), with Social Responsiveness Scale score ≥76. Headache was reported by 49.6% (61/123) of children over 5 years old, and 25.2% (31/123; 10 girls, 21 boys) reported migraine. Other neurological comorbidities included 20 cases of epilepsy (13.8%), 11 cases of optic nerve glioma (7.6%), five cases of brain tumor (3.4%), six cases of cerebrovascular disease (4.1%), and two cases of hydrocephalus (1.4%).

Conclusion: Intellectual problems, ADHD, autism spectrum disorder, and migraine are major neurological comorbidities in NF1.

Keywords: attention deficit-hyperactivity disorder; autism; comorbidity; migraine; neurofibromatosis type 1.