Clinical Images: Imaging Manifestations of Orbital Neurofibromatosis Type 1

Neurofibromin belongs to the family of GTPase-activating proteins and is found in many organs such as the brain, kidney, spleen, and thymus. 2 The disease demonstrates 100% penetrance but has high variability of expression. 3 Patients with the same NF1 gene mutation often display different clinical manifestations of NF1. 4 Some common clinical manifestations include café au lait macules, axillary or inguinal freckling, Lisch nodules (iris hamartomas), and neurofibromas. 2, 5 Café au lait spots—flat hyperpigmented macules—are the earliest clinical finding in NF1. [...]the right globe was enlarged, consistent with buphthalmos (Figure 4). [image omitted: see PDF] DISCUSSION Diagnosis of NF1 requires the presence of at least 2 of the following clinical features: at least 6 café au lait spots (>5 mm in diameter if the patient is prepubertal or >15 mm diameter postpuberty), at least 2 neurofibromas (1 if plexiform), freckling in the axillary or inguinal region, optic glioma, at least 2 Lisch nodules, distinctive body lesions (sphenoid dysplasia or pseudarthrosis), or a known first-degree relative with NF1. 7 Our patient met the criteria with café au lait spots, plexiform neurofibroma, and sphenoid dysplasia. [...]congenital or infantile glaucoma is typically the cause of buphthalmos in patients who do not have NF1. Because the sclera is soft and deformable at an early age, this manifestation is almost uniquely seen during childhood.12 Common CNS manifestations of NF1 that were not seen in our patient include FASIs, optic nerve gliomas, parenchymal gliomas, and dural ectasia of the optic nerve sheath and spinal canal. The globus pallidus of the basal ganglia is the most frequently involved site.13 FASIs in the setting of NF1 are usually transient and asymptomatic, occurring in patients aged 4-12 years and regressing by adulthood.14 Approximately 80% of children with NF1 experience moderate to severe cognitive impairment.13 Studies have shown a relationship between FASIs and cognitive dysfunction in patients with NF1.15-18 Hyman and colleagues found that children with NF1 and discrete FASI lesions in the thalamus specifically, a relatively rare location for T2 hyperintensity (approximately 8% of cases), score 18 intellectual quotient points lower than children without discrete thalamic lesions.19 Optic nerve glioma is the most common primary tumor of the optic nerve.