Prospective evaluation of the brain in asymptomatic children with neurofibromatosis type 1: relationship of macrocephaly to T1 relaxation changes and structural brain abnormalities

BACKGROUND AND PURPOSE: Mutation of the neurofibromatosis type 1 (NF-1) gene may be associated with abnormal growth control in the brain. Because macrocephaly could be a sign of abnormal brain development and because 30 % to 50 % of children with NF-1 display macrocephaly in the absence of hydrocephalus, we sought to determine the relationship between macrocephaly and other brain abnormalities in young subjects with NF-1. These subjects were free of brain tumor, epilepsy, or other obvious neurologic problems. METHODS: We prospectively screened 18 neurologically asymptomatic subjects with NF-1, ages 6 to 16 years, using clinical measures, psychometric testing, conventional MR imaging, and quantitative MR imaging to measure T1. RESULTS: Cranial circumference was 2 or more SDs above the age norm in seven (39%) of 18 subjects, a frequency of macrocephaly 17-fold higher than normal. Conventional MR imaging showed abnormalities in all 18 children, although there were more extensive abnor-malities in subjects with macrocephaly. Macrocephaly in NF-1 was associated with enlargement of multiple brain structures, and brain T1 in macrocephalic subjects was reduced with respect to controls in the genu, frontal white matter, caudate, putamen, thalamus, and cortex. In nor