Calvarial defects and skeletal dysplasia in patients with neurofibromatosis Type 1.

OBJECT: 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.

METHODS

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.

RESULTS

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 0.4-20.0 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.

CONCLUSIONS

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.