Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the “NF1 facies”
Section snippets
Background
Neurofibromatosis type 1 (NF1, also known as von Recklinghausen's disease) is a genetic disorder with an autosomal dominant pattern of inheritance involving the skin, skeletal, and neural tissues, and affects 1 in 3000 births with no gender or race predilection (Friedman et al., 1999). Individuals with NF1 are heterozygous (haploinsufficient) for a loss-of-function mutation in NF1, the gene that encodes the tumor suppressor neurofibromin, which negatively regulates the activity of the
Methods
Retrospective ascertainment of patients and phenotype data. A total of 80 adults were included in the study, but two adult patient-control pairs were excluded due to anomalously low measurements, yielding a total of 78 adult case-control pairs for our final analysis. These patients were diagnosed with NF1 per the NIH consensus criteria (National Institutes of Health Consensus Development Conference, 1988) and evaluated at the National Institutes of Health (NIH) in Bethesda, MD as part of the
Results
Patient demographics. Patient characteristics are summarized in Table 2. In the adult study, there were 33 males (42%) and 45 females (58%). In the pediatric study, there were 14 males (61%) and 9 females (39%). All subjects were white.
Cephalometric analyses in cases and controls. Analyses of difference in 16 cephalometric measurements between cases and controls are shown in Table 3 (adults) and in Table 4 (children); these analyses stratified by gender are shown in Supplemental Tables 1 and 2
Discussion
In our study of 101 persons with NF1 (78 adults and 23 children) with age-, ethnicity- and gender-matched controls, we found a shorter maxilla, mandible, cranial base, (especially anteriorly) and diminished facial height in adults, but not children, with NF1. The cranial base angle was significantly more oblique in adults with NF1. Some measures of facial height, mandible size and anterior cranial base correlated with height, less so with head circumference and not at all with interpupillary
Conclusions
In our study of 101 persons with NF1 (78 adults and 23 children) with age-, ethnicity- and gender-matched controls, we found a shorter maxilla, mandible, cranial base, (especially anteriorly) and diminished facial height in adults, but not children, with NF1. 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. Hypertelorism was
Author contributions
WC, LF, NK, ER and DS analyzed data. PG, CB, AB, BW and DS evaluated patients. WC, LF, NK and DS wrote the paper. All authors reviewed the final draft of the manuscript.
Acknowledgments
This work was supported by the Division of Cancer Epidemiology and Genetics (DCEG) and the Center for Cancer Research of the National Cancer Institute's Intramural Research Program. We thank Janice Lee DDS, MD (NIDCR) for helpful discussions.
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