Short mandible, maxilla and cranial base are common in patients with neurofibromatosis 1

Heervä, Eetu; Peltonen, Sirkku; Pirttiniemi, Pertti; Happonen, Risto‐Pekka; Visnapuu, Vivian

doi:10.1111/j.1600-0722.2011.00811.x

Cited by 24 publications

(27 citation statements)

References 38 publications

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“…In this dataset of American whites with NF1, we confirmed (in a modestly larger sample) many of the findings found by Heerva et al . [8] in an NF1 Finnish cohort.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is also hypothesized to develop due to a primary bone cell-autonomous defect [5]. An analysis of NF1 cephalometry was first published by Heervä et al in 2011, who found that individuals with NF1 typically had a shorter mandible, maxilla and cranial base compared to controls [8]. The sphenoid bone is a key component of the anterior cranial base.…”

Section: Introductionmentioning

confidence: 99%

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Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the “NF1 facies”

Cung

Freedman

Khan

et al. 2015

European Journal of Medical Genetics

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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.

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“…In this dataset of American whites with NF1, we confirmed (in a modestly larger sample) many of the findings found by Heerva et al . [8] in an NF1 Finnish cohort.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the “NF1 facies”

Cung

Freedman

Khan

et al. 2015

European Journal of Medical Genetics

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“…On prenatal ultrasonography, maxillary hypoplasia can appear as an incidental finding or can be part of a structural malformation, a genetic syndrome or a chromosomal anomaly . When searching the literature and the Online Mendelian Inheritance in Men database, the term maxillary hypoplasia results in syndrome citations, such as Marfan syndrome and genetic disorders such as Neurofibromatosis type 1 . Additionally, maxillary hypoplasia has been described as a consistent clinical finding in fetuses and newborns with Down syndrome .…”

Section: Discussionmentioning

confidence: 99%

“…Visualization of the fetal maxillary bone is possible from early weeks of gestation onwards and important information can be drawn from the examination of abnormal fetal maxillary development . During routine prenatal evaluation, maxillary hypoplasia may occur as an isolated finding, but may also lead to the detection of structural abnormalities, genetic disorders or syndromes . Thus, it is clinically relevant to have normative curves of maxillary growth pattern of normal fetuses to allow the diagnosis of pathologies as early during pregnancy as possible .…”

Section: Introductionmentioning

confidence: 99%

Maxillary dental arch biometry: assessment with fetal MR imaging

et al. 2012

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“…NF1 is characterized by the predisposition to benign and malignant tumors of the peripheral and central nervous system. NF1 patients may also exhibit noncancerous symptoms such as the presence of café-au-lait macules, axial freckling, learning disabilities, and skeletal dysplasia [2,3]. Clinically, NF1 patients exhibit skeletal congenital or developmental abnormalities, resulting in alterations in bone shape or size.…”

Section: Introductionmentioning

confidence: 99%

An Osteoblast Origin for Craniofacial Dysplasia in Neurofibromatosis Type I

Bamaga¹,

O'Sullivan²,

Schmitz³

et al. 2017

JDHODT

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Sphenoid wing dysplasia (SWD), which results in a craniofacial deformity, is the third most common skeletal deformity in Neurofibromatosis Type I (NF1) patients. A neurofibromin osteoblast conditional deletion mouse model (Nf1ob-/-) has been developed to study the skeletal abnormalities in NF1. No overt morphological phenotype is seen in the appendicular or axial skeleton of these mice. Nf1ob-/-mice have been shown to have increased bone porosity and lower bone density. We noted a progressive craniofacial deformity, which results in cranial asymmetry, malocclusion and unilateral proptosis of an eye. To assess this deformity, we employed micro-computed tomography (µCT) and geometric morphometric analysis to compare Nf1ob-/-mouse skulls to control animals. Landmarks were placed on the images at 13 biologically relevant cranial anatomical sites. Analysis of distances and angles between these landmarks revealed that there is significant variation between the Nf1ob-/-mice and controls. We found that the nasal and frontal bones of Nf1ob-/-mice skulls are deviated from the central line, whereas it was straight in controls. The nasal region is tipped downward in Nf1ob-/-mice. We also noted that the cranium shows a trend toward macrocephaly in Nf1ob-/-mice whereas other measurements were within the range of normal control mice. These differences correspond to those seen in craniofacial dysplasia and SWD in NF1 patients. No tumors were found associated with the craniofacial dysplasia in Nf1ob-/-mice. Our results identify a primarily osteoblast origin for the pathogenesis of craniofacial dysplasia in Nf1ob-/-mice and strongly support an osteoblast origin for SWD in NF1. In addition, we identify and validate a novel mouse model with which to explore molecular mechanisms and test preventative treatments for SWD in NF1.

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Short mandible, maxilla and cranial base are common in patients with neurofibromatosis 1

Cited by 24 publications

References 38 publications

Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the “NF1 facies”

Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the “NF1 facies”

Maxillary dental arch biometry: assessment with fetal MR imaging

An Osteoblast Origin for Craniofacial Dysplasia in Neurofibromatosis Type I

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