Neurofibromatosis type 1 is a common neurogenetic disorder characterized by significant clinical variability. As such, numerous studies have focused on identifying clinical, radiographic, or molecular biomarkers that predict the occurrence or progression of specific clinical features in individuals with neurofibromatosis type 1. One of these clinical biomarkers, macrocephaly, has been proposed as a prognostic factor for optic pathway glioma development. In the current study, the authors demonstrate that macrocephaly is not associated with the development of these brain tumors or the need to institute treatment for clinical progression. These findings suggest that macrocephaly is not a robust biomarker of optic pathway glioma formation or progression in children with neurofibromatosis type 1.
SoucyEAGaoFGutmannDHDunnCM. Developmental delays in children with neurofibromatosis type 1. J Child Neurol. 2012;27(5):641–644.
2.
HymanSLShoresANorthKN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology. 2005;65:1037–1044.
3.
PayneJMHymanSLShoresEANorthKN. Assessment of executive function and attention in children with neurofibromatosis type 1: relationships between cognitive measures and real-world behavior. Child Neuropsychol. 2011;17:313–329.
4.
ConstantinoJNZhangYHolzhauerK. Distribution and within-family specificity of quantitative autistic traits in patients with neurofibromatosis type 1. J Pediatr. 2015;167(3):621–626.
5.
WesselLEAlbersACGutmannDHDunnCM. The association between hypotonia and brain tumors in children with neurofibromatosis type 1. J Child Neurol. 2013;28(12):1664–1667.
6.
SchinderaCWingeierKGoeggelSB. Macrocephaly in neurofibromatosis type 1: a sign post for optic pathway gliomas?Childs Nerv Syst. 2011;27(12):2107–2111.
7.
BaleSJAmosCIParryDMBaleAE. Relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type 1. Am J Med Genet. 1991;40(2):206–210.
8.
ClementiMMilaniSMammiI. Neurofibromatosis type 1 growth charts. Am J Med Genet. 1999;87(4):317–323.
9.
KarvonenMSaariAHannilaML. Elevated head circumference-to-height ratio is an early and frequent feature in children with neurofibromatosis type 1. Horm Res Paediatr. 2013;79(2):97–102.
10.
GreenwoodRSTuplerLAWhittJK. Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1. Arch Neurol. 2005;62(12):1904–1908.
11.
MargaritiPNBlekasKKatziotiFG. Magnetization transfer ratio and volumetric analysis of the brain in macrocephalic patients with neurofibromatosis type 1. Eur Radiol. 2007;17(2):433–438.
12.
FaulFErdfelderELangAGBuchnerA. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–191.
13.
National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. Arch Neurol. 1988;45(5):575–578
14.
ListernickRFernerRELiuGT. Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations. Ann Neurol. 2007;61(3):189–198.
15.
SzudekJBirthPFriedmanJM. Growth in North American white children with neurofibromatosis 1 (NF1). J Med Genet. 2000;37:933–938.
16.
CnossenMHMoonsKGGarssenMP. Minor disease features in neurofibromatosis type 1 (NF1) and their possible value in diagnosis of NF1 in children < or = 6 years and clinically suspected of having NF1. Neurofibromatosis team of Sophia Children’s Hospital. J Med Genet. 1998;35(8):624–627.
17.
SteenRGTaylorJSLangstonJW. Prospective evaluation of the brain in asymptomatic children with neurofibromatosis type 1: relationship of macrocephaly to T1 relaxation changes and structural brain abnormalities. Am J Neuroradiol. 2001;22(5):810–817.
18.
SaidSMYehTLGreenwoodRS. MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis. Neuroreport. 1996;7:1941–1944.
19.
MooreBDSlopisJMJacksonEF. Brain volume in children with neurofibromatosis type 1: relation to neuropsychological status. Neurology. 2000;54(4):914–920.
20.
HuijbregtsSCLoitfelderMRomboutsSA. Cerebral volumetric abnormalities in Neurofibromatosis type 1: associations with parent ratings of social and attention problems, executive dysfunction, and autistic mannerisms. J Neurodev Disord. 2015;7:32.
21.
BennettMRRizviTAKaryalaS. Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants. J Neurosci. 2003;23(18):7207–7217.
BajenaruMLHernandezMRPerryA. Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Cancer Res. 2003;63(24):8573–8577.
24.
FuquaJSBerkovitzGD. Growth hormone excess in a child with neurofibromatosis type 1 and optic pathway tumor: a patient report. Clin Pediatr (Phila). 1998;37(12):749–752.
25.
DrimmieFMMacLennanACNicollJA. Gigantism due to growth hormone excess in a boy with optic glioma. Clin Endrocinol (Oxf). 2000;52(4):535–538.
26.
SpiegelMOexleKHornD. Childhood overgrowth in patients with common NF1 microdeletions. Eur J Hum Genet. 2005;13(7):883–888.
27.
BrzowskiAEBazanC IIIMummaJVRyanSG. Spontaneous regression of optic glioma in a patient with neurofibromatosis. Neurology. 1992;42(3 pt 1):679–681.
28.
PerilongoGMorasPCarolloC. Spontaneous partial regression of low-grade glioma in children with neurofibromatosis-1: a real possibility. J Child Neurol. 1999;14(6):352–356.
29.
ParsaCFHoytCSLesserRL. Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging. Arch Ophthalmol. 2001;119(4):516–529.
