{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T09:06:07Z","timestamp":1789722367143,"version":"4.0.1"},"reference-count":46,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PED"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Skull defects, including sphenoid dysplasia and calvarial defects, are rare but distinct findings in patients with neurofibromatosis Type 1 (NF1). The underlying pathophysiology is unclear. The goal of this study was to identify the clinical characteristics and natural history of skull defects in patients with NF1.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>An electronic search engine of medical records was used to identify patients with NF1 and bony skull anomalies. All clinical, radiographic, pathology, and operative reports were reviewed. The relationship between bony anomalies and significant clinical associations was evaluated. This study received institutional review board approval.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Twenty-one patients were identified. The mean age at NF1 diagnosis was 4.2 years. The mean age at skull defect diagnosis was 8.8 years (9.7 years in the sphenoid wing dysplasia group and 11.9 years in the calvarial defect group). Sphenoid dysplasia was associated with a plexiform neurofibroma or dural ectasia in 73.3% and 80.0% of cases, respectively. Calvarial defects were associated with a plexiform neurofibroma or dural ectasia in 66.7% and 33.3% of patients, respectively. An absence of either an associated neurofibroma or ectasia was not noted in any patient with sphenoid wing dysplasia or 25.0% of those with calvarial defects. In 6 patients, both types of skull defects presented simultaneously. Serial imaging studies were obtained for a mean follow-up time of 7.5 years (range 0.4\u201320.0 years). Of these patients with serial imaging, radiographic progression was found in 60% of cases of calvarial defects and 56% of cases of sphenoid wing dysplasia. Two patients underwent surgical repair of a skull defect, and both required repeat procedures.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The majority of skull defects in patients with NF1 were associated with an adjacent structural lesion, such as a plexiform neurofibroma or dural ectasia. This findings from this cohort also support the concept of progression in defect size in more than half of the patients. Potential mechanisms by which these secondary lesions contribute to pathogenesis of the bony defect may include changes in the bony microenvironment. A better understanding of the pathophysiology of skull defects will help guide detection, improve treatment and outcome, and may contribute to the understanding of the pathogenesis of bony lesions in NF1.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2013.1.peds12409","type":"journal-article","created":{"date-parts":[[2013,2,15]],"date-time":"2013-02-15T15:02:29Z","timestamp":1360940549000},"page":"410-416","source":"Crossref","is-referenced-by-count":49,"title":["Calvarial defects and skeletal dysplasia in patients with neurofibromatosis Type 1"],"prefix":"10.3171","volume":"11","author":[{"given":"Daniel K.","family":"Arrington","sequence":"first","affiliation":[{"name":"Departments of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Danehy","sequence":"additional","affiliation":[{"name":"Radiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Analise","family":"Peleggi","sequence":"additional","affiliation":[{"name":"Departments of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Proctor","sequence":"additional","affiliation":[{"name":"Neurosurgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira B.","family":"Irons","sequence":"additional","affiliation":[{"name":"Medicine, Boston Children's Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole J.","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Departments of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-peds12409","series-title":"Am J Med Genet A","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1002\/ajmg.a.31754","article-title":"Associations of osseous abnormalities in Neurofibromatosis 1","volume":"143A","author":"Alwan","year":"2007"},{"key":"b2-peds12409","series-title":"Clin Genet","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1111\/j.1399-0004.2005.00410.x","article-title":"Is osseous dysplasia a primary feature of neurofibromatosis 1 (NF1)?","volume":"67","author":"Alwan","year":"2005"},{"key":"b3-peds12409","series-title":"AJNR Am J Neuroradiol","first-page":"1253","article-title":"Lacunarlike skull in neurofibromatosis","volume":"11","author":"Barnowsky","year":"1990"},{"key":"b4-peds12409","series-title":"Mol Genet Metab","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.ymgme.2007.12.004","article-title":"Generalized metabolic bone disease in Neurofibromatosis type I","volume":"94","author":"Brunetti-Pierri","year":"2008"},{"key":"b5-peds12409","series-title":"Br J Radiol","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1259\/0007-1285-51-610-771","article-title":"Orbitocranial asymmetry","volume":"51","author":"Burrows","year":"1978"},{"key":"b6-peds12409","series-title":"Acta Neurochir (Wien)","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/BF01400853","article-title":"Massive osteolysis of the skull: long-term follow-up observations after cranioplasty. Report of two cases","volume":"73","author":"Chai","year":"1984"},{"key":"b7-peds12409","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"480","DOI":"10.3171\/jns.2000.93.3.0480","article-title":"An unusual pterygopalatine meningocele associated with neurofibromatosis type 1. Case report","volume":"93","author":"Chapman","year":"2000"},{"key":"b8-peds12409","series-title":"J Craniofac Surg","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1097\/00001665-199805000-00020","article-title":"Neurofibromatosis of the orbit and skull base","volume":"9","author":"Clauser","year":"1998"},{"key":"b9-peds12409","series-title":"Am J Med Genet","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/(SICI)1096-8628(19991203)87:4<317::AID-AJMG7>3.0.CO;2-X","article-title":"Neurofibromatosis type 1 growth charts","volume":"87","author":"Clementi","year":"1999"},{"key":"b10-peds12409","series-title":"J Craniofac Surg","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1097\/SCS.0b013e31824e645f","article-title":"Tissue interactions between craniosynostotic dura mater and bone","volume":"23","author":"Cooper","year":"2012"},{"key":"b11-peds12409","series-title":"Orthop Clin North Am","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ocl.2007.03.008","article-title":"Scoliosis associated with neurofibromatosis","volume":"38","author":"Crawford","year":"2007"},{"key":"b12-peds12409","series-title":"J Am Acad Orthop Surg","doi-asserted-by":"publisher","first-page":"217","DOI":"10.5435\/00124635-199907000-00002","article-title":"Neurofibromatosis in children: the role of the orthopaedist","volume":"7","author":"Crawford","year":"1999"},{"key":"b13-peds12409","series-title":"J Pediatr Orthop","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1097\/01241398-198601000-00015","article-title":"Osseous manifestations of neurofibromatosis in childhood","volume":"6","author":"Crawford","year":"1986"},{"key":"b14-peds12409","series-title":"J Pediatr Orthop","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1097\/01.bpb.0000271310.87997.ae","article-title":"Decreased bone mineral density in neurofibromatosis type 1: results from a pediatric cohort","volume":"27","author":"Dulai","year":"2007"},{"key":"b15-peds12409","series-title":"Am J Hum Genet","first-page":"305","article-title":"An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes","volume":"53","author":"Easton","year":"1993"},{"key":"b16-peds12409","series-title":"Am J Med Genet","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(SICI)1096-8628(19990326)89:1<1::AID-AJMG3>3.0.CO;2-8","article-title":"Epidemiology of neurofibromatosis type 1","volume":"89","author":"Friedman","year":"1999"},{"key":"b17-peds12409","series-title":"Anticancer Res","first-page":"1751","article-title":"Dysplasia of the orbit and adjacent bone associated with plexiform neurofibroma and ocular disease in 42 NF-1 patients","volume":"30","author":"Friedrich","year":"2010"},{"key":"b18-peds12409","series-title":"Plast Reconstr Surg","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1097\/01.PRS.0000070728.56716.51","article-title":"Osteogenesis in calvarial defects: contribution of the dura, the pericranium, and the surrounding bone in adult versus infant animals","volume":"112","author":"Gosain","year":"2003"},{"key":"b19-peds12409","series-title":"Bone","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.bone.2010.06.001","article-title":"Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity, aberrant morphology, and resistance to serum deprivation","volume":"47","author":"Heerv\u00e4","year":"2010"},{"key":"b20-peds12409","series-title":"Osteoporos Int","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s001980170032","article-title":"Decreased bone mineral density in neurofibromatosis-1 patients with spinal deformities","volume":"12","author":"Ill\u00e9s","year":"2001"},{"key":"b21-peds12409","series-title":"AJNR Am J Neuroradiol","first-page":"644","article-title":"Reassessment of sphenoid dysplasia associated with neurofibromatosis type 1","volume":"23","author":"Jacquemin","year":"2002"},{"key":"b22-peds12409","series-title":"AJNR Am J Neuroradiol","first-page":"1678","article-title":"Orbit deformities in craniofacial neurofibromatosis type 1","volume":"24","author":"Jacquemin","year":"2003"},{"key":"b23-peds12409","series-title":"AJR Am J Roentgenol","doi-asserted-by":"publisher","first-page":"413","DOI":"10.2214\/ajr.180.2.1800413","article-title":"MR imaging of spinal tumors in children with neurofibromatosis 1","volume":"180","author":"Khong","year":"2003"},{"key":"b24-peds12409","series-title":"J Med Genet","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1136\/jmg.2006.041095","article-title":"Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1","volume":"43","author":"Lammert","year":"2006"},{"key":"b25-peds12409","series-title":"Osteoporos Int","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1007\/s00198-005-1940-2","article-title":"Decreased bone mineral density in patients with neurofibromatosis 1","volume":"16","author":"Lammert","year":"2005"},{"key":"b26-peds12409","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1227\/00006123-199507000-00020","article-title":"Absence of the greater sphenoid wing in neurofibromatosis type I: congenital or acquired: case report","volume":"37","author":"Macfarlane","year":"1995"},{"key":"b27-peds12409","series-title":"Neuroradiology","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/BF00455739","article-title":"Computed tomography of lambdoid calvarial defect in neurofibromatosis. A case report","volume":"25","author":"Mann","year":"1983"},{"issue":"6 Suppl","key":"b28-peds12409","series-title":"J Neurosurg","first-page":"484","article-title":"Calvarial defects associated with neurofibromatosis type 1. Report of two cases","volume":"106","author":"Mislow","year":"2007"},{"key":"b29-peds12409","series-title":"Neurofibromatosis","first-page":"172","article-title":"Neurofibromatosis. Bethesda, Md, USA, July 13\u201315, 1987","volume":"1","author":"National Institutes of Health Consensus Development Conference Statement","year":"1988"},{"key":"b30-peds12409","series-title":"Cells Tissues Organs","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1159\/000075027","article-title":"Regulation of cranial suture morphogenesis","volume":"176","author":"Ogle","year":"2004"},{"key":"b31-peds12409","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3171\/jns.1977.46.2.0245","article-title":"\u201cCongenital\u201d plexiform neurofibroma of the occipital scalp. Case report","volume":"46","author":"Ohaegbulam","year":"1977"},{"key":"b32-peds12409","series-title":"Genes Dev","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1101\/gad.990702","article-title":"FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease","volume":"16","author":"Ornitz","year":"2002"},{"key":"b33-peds12409","series-title":"J Spinal Disord Tech","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1097\/01.bsd.0000133466.97241.50","article-title":"Wholespine magnetic resonance imaging in patients with neurofibromatosis type 1 and spinal deformity","volume":"17","author":"Ramachandran","year":"2004"},{"key":"b34-peds12409","series-title":"Br J Plast Surg","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/S0007-1226(03)00151-6","article-title":"Massive plexiform neurofibroma with associated meningo-encephalocoele and occipital bone defect presenting as a cervical mass","volume":"56","author":"Renshaw","year":"2003"},{"key":"b35-peds12409","series-title":"Am J Roentgenol Radium Ther Nucl Med","doi-asserted-by":"publisher","first-page":"319","DOI":"10.2214\/ajr.105.2.319","article-title":"Calvarial bone defects in neurofibromatosis","volume":"105","author":"Saha","year":"1969"},{"key":"b36-peds12409","series-title":"Pediatr Radiol","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00247-003-0927-4","article-title":"Atypical meningioma and extensive calvarium defects in neurofibromatosis type 1","volume":"33","author":"Simsek","year":"2003"},{"key":"b37-peds12409","series-title":"J Pediatr","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jpeds.2006.10.048","article-title":"Bone mineral density in children and adolescents with neurofibromatosis type 1","volume":"150","author":"Stevenson","year":"2007"},{"key":"b38-peds12409","series-title":"J Pediatr Endocrinol Metab","first-page":"169","article-title":"Pediatric 25-hydroxyvitamin D concentrations in neurofibromatosis type 1","volume":"24","author":"Stevenson","year":"2011"},{"key":"b39-peds12409","series-title":"Am J Med Genet","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/(SICI)1096-8628(20000529)92:3<224::AID-AJMG12>3.0.CO;2-J","article-title":"Growth charts for young children with neurofibromatosis 1 (NF1)","volume":"92","author":"Szudek","year":"2000"},{"key":"b40-peds12409","series-title":"Clin Genet","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1111\/j.1399-0004.2007.00886.x","article-title":"Increased dental caries in people with neurofibromatosis 1","volume":"72","author":"Tucker","year":"2007"},{"key":"b41-peds12409","series-title":"J Med Genet","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1136\/jmg.2008.061895","article-title":"Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1)","volume":"46","author":"Tucker","year":"2009"},{"issue":"401","key":"b42-peds12409","series-title":"Clin Orthop Relat Res","first-page":"107","article-title":"Orthopaedic manifestations of neurofibromatosis in children: an update","author":"Vitale","year":"2002"},{"key":"b43-peds12409","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"3910","DOI":"10.1093\/hmg\/ddr310","article-title":"Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I","volume":"20","author":"Wang","year":"2011"},{"key":"b44-peds12409","series-title":"J Cell Biochem","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1002\/jcb.24160","article-title":"Fibroblast growth factor-2 promotes catabolism via FGFR1-Ras-Raf-MEK1\/2-ERK1\/2 axis that coordinates with the PKC\u03b4 pathway in human articular chondrocytes","volume":"113","author":"Yan","year":"2012"},{"key":"b45-peds12409","series-title":"Acta Paediatr","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1111\/j.1651-2227.2007.00401.x","article-title":"Bone mineral density in children with neurofibromatosis 1","volume":"96","author":"Yilmaz","year":"2007"},{"key":"b46-peds12409","series-title":"Bone","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.bone.2005.01.022","article-title":"Neurofibromin and its inactivation of Ras are prerequisites for osteoblast functioning","volume":"36","author":"Yu","year":"2005"}],"container-title":["Journal of Neurosurgery: Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/11\/4\/article-p410.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/11\/4\/article-p410.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/11\/4\/article-p410.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T14:21:04Z","timestamp":1681568464000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/11\/4\/article-p410.xml"}},"subtitle":["Clinical article"],"short-title":[],"issued":{"date-parts":[[2013,4]]},"references-count":46,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3171\/2013.1.peds12409","relation":{},"ISSN":["1933-0707","1933-0715"],"issn-type":[{"value":"1933-0707","type":"print"},{"value":"1933-0715","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4]]}}}