J Neurosurg (6 Suppl Pediatrics) 106:484–489, 2007 484 J. Neurosurg: Pediatrics / Volume 106 / June, 2007 EUROFIBROMATOSIS Type 1 is a neurocutaneous dis- order affecting approximately one in 3000 persons worldwide. 16 The main clinical features are cutane- ous neurofibromas, café au lait spots, and Lisch nodules. Less common manifestations include axillary or inguinal freckling and neural sheath tumors. 6 Neurofibromatosis Type 1 is caused by mutations in the NF1 tumor suppressor gene, located on chromosome 17q11.2. Neurofibromin, the NF1 gene product, is a potent down-regulator of Ras pro- teins, which control cellular functions such as proliferation, differentiation, and apoptosis. Loss of heterozygosity for the NF1 gene results in elevated levels of Ras–guanosine triphosphate in cells and the formation of neurofibromas, a characteristic lesion in patients with NF1. 7,35 Inheritance is autosomal dominant, although more than 50% of cases rep- resent new mutations and 80% of inherited cases are of pa- ternal origin. 6 Osseous manifestations have been reported in approxi- mately 50% of patients with NF1. 8,18 The most common anomalies are scoliosis (10–26% of patients), absence of the greater sphenoid wing (3–11.3%), tibial pseudarthrosis (1– 4%), short stature, spinal meningocele, and macrocephaly. 6 Calvarial involvement in patients with NF1 is uncommon, however there have been several reports of defects in the oc- cipital and parietal cranium. 9,17,18,21,33 In most of these cases, it was unclear whether the bone gap was congenital or ac- quired. We present the cases of two patients with NF1 who experienced progressive, massive calvarial osteolysis and were treated with different operative strategies. The dispar- ate outcome of each cranioplastic method provides insight into the pathogenesis of these lesions. Case Reports Case 1 History and Examination. This 15-year-old boy with neu- rofibromatosis and Noonan syndrome was evaluated for two enlarging occipital defects. He was born at 37 weeks of ges- tation via spontaneous vaginal delivery after an unremark- able pregnancy. His parents and two older siblings were healthy and there was no family history of neurofibroma- tosis. When he was 5 years of age, he had a neurosurgical evaluation for two previously undetected calvarial defects. On physical examination, he was noted to be short for his age and had obvious developmental delays (IQ testing revealed that his full-scale IQ was in the first percentile for his age, according to the serial Wechsler Intelligence Scale for Children, Third Edition). He had other features seen in patients with NF1 including multiple café au lait spots and a large plexiform neurofibroma involving the left ear and oc- cipital scalp. There were palpable bone defects in the left oc- Calvarial defects associated with neurofibromatosis Type 1 Report of two cases JOHN M. K. MISLOW, M.D., PH.D., 1 MARK R. PROCTOR, M.D., 1 P. DANIEL MCNEELY , M.D., 2 ARIN K. GREENE, M.D., M.M.SC., 3 AND GARY F. ROGERS, M.D., J.D., M.B.A., M.P.H. 3 Departments of 1 Neurosurgery and 3 Plastic Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts; and 2 Division of Neurosurgery, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada Calvarial osteolysis is a relatively rare finding in patients with neurofibromatosis. The authors describe two patients with neurofibromatosis Type 1 (NF1) and extensive cranial defects associated with underlying dural ectasia. Cranio- plasties were performed in both patients with mixed results. One patient underwent cranioplasty using titanium mesh and methylmethacrylate. The other patient underwent an extensive cranioplasty with autogenous iliac crest grafting, and after initial healing has since had further bone resorption. In conclusion, the results of cranial reconstruction in patients with NF1 and dural ectasia are unpredictable because of the tendency for further bone resorption; techniques that pro- tect the graft material from cerebrospinal fluid pulsations via a rigid mesh should be considered. KEY WORDS • calvarium • skull defect • neurofibromatosis • pediatric neurosurgery N Abbreviations used in this paper: CSF = cerebrospinal fluid; CT = computed tomography; ICP = intracranial pressure; NF1 = neurofi- bromatosis Type 1.