title: Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the "NF1 facies".
abstract: BACKGROUND
  Neurofibromatosis type 1 (NF1) is a common, autosomal dominant tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Cephalometry is an inexpensive, readily available and non-invasive technique that is under-utilized in studying the NF1 craniofacial phenotype. An analysis of NF1 cephalometry was first published by Heervä et al. in 2011. We expand here on that first investigation with a larger cohort of adult and pediatric patients affected with NF1 and sought objective insight into the NF1 facies, said to feature hypertelorism and a broad nasal base, from cephalometric analysis.
  
  
  METHODS
  We obtained cephalograms from 101 patients with NF1 (78 adults and 23 children) from two NF1 protocols at the National Institutes of Health. Each subject had an age-, gender- and ethnicity-matched control. We used Dolphin software to make the cephalometric measurements. We assessed the normality of differences between paired samples using the Shapiro-Wilk test and evaluated the significance of mean differences using paired t-tests and adjusted for multiple testing. We explored the relationship between the cephalometric measurements and height, head circumference and interpupillary distance.
  
  
  RESULTS
  In this dataset of American whites with NF1, we confirmed in a modestly larger sample many of the findings found by Heerva et al. in an NF1 Finnish cohort. We found a shorter maxilla, mandible, cranial base, (especially anteriorly, p = 0.0001) and diminished facial height in adults, but not children, with NF1. Only one adult exhibited hypertelorism.
  
  
  CONCLUSIONS
  The cephalometric differences in adults arise in part from cranial base shortening and thus result in a shorter face, mid-face hypoplasia, reduced facial projection, smaller jaw, and increased braincase globularity. In addition, we suggest that NF1 sphenoid bone shortening, a common event, is consistent with an intrinsic NF1 bone cell defect, which renders the bone more vulnerable to a random "second hit" in NF1, leading to sphenoid wing dysplasia, a rare event.
authors.affiliation: University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Winnie
authors.initials: W
authors.lastname: Cung
authors.affiliation: University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Freedman
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Khan
authors.affiliation: University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Romberg
authors.affiliation: Dental Consult Service, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Gardner
authors.affiliation: Dental Consult Service, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carol W
authors.initials: CW
authors.lastname: Bassim
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Baldwin
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Brigitte C
authors.initials: BC
authors.lastname: Widemann
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Electronic address: drstewart@mail.nih.gov.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental / Q000473:pathology*; D002508:Cephalometry; D002648:Child; D019066:Facies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000473:pathology*; D013100:Sphenoid Bone / Q000254:growth & development / Q000473:pathology*
keywords: Cephalometery; Dysmorphology; Neurofibromatosis type 1; Sphenoid wing dysplasia