Severe orbito-cranial changes in Neurofibromatosis Type 1

12-year female presenting with chronic right-sided progressive face disfigurement, bulging right eyeball, swelling in right orbital and facial region & severe right eye vision loss. Multiple Lisch nodules seen in iris with multiple café au lait spots in torso. No similar complaints in siblings/family members.

MRI revealed severe right sphenoid wing and temporal bone dysplasia. Exophthalmos and buphthalmos of right eyeball seen with posteriorly dislocated eye lens. Intraocular V-shaped membrane is seen in posterior chamber representing retinal detachment (Figure 1).

Poorly-defined lesion in right orbital intraconal and extraconal regions, contiguously extending into periorbital region, infratemporal fossa, right cavernous sinus (Figure 2), bilateral parotid regions (Figure 3) showing T2 hypointense central focus (target sign) representing plexiform neurofibroma (PNF).

T2/FLAIR hyperintense lesions seen in bilateral basal ganglia, thalamus, and right cerebellar hemisphere, representing focal altered signal intensity (FASI) (Figure 4).

Enlargement of right middle cranial fossa seen with dilatation of right lateral ventricle (Figure 5).

Herniation of right basi-frontal lobe into right orbit through orbital roof defect (Figure 6).

Severe atrophy of right optic nerve seen. No optic nerve glioma was seen on plain MRI (Figure 7). Left orbit, left optic nerve appears normal.

Neurofibromatosis type 1 (NF1)/von Recklinghausen disease is one of the most common multisystem neurocutaneous disorders, characterized by the inactivation of NF1 gene at chromosome 17q11.2- encoding for neurofibromin, which acts as a tumor suppressor of the Ras/MAPK pathway (hence also classified as RASopathy) [1]. Inactivation of the gene predisposes to multiple tumors and hamartoma development [1,2,3].

About half of the cases are autosomal dominant while the rest are due to de novo mutation [2].

Clinical diagnosis is made by the presence of 2 or more of the criteria, namely >6 café au lait spots, PNF/>1 neurofibroma, optic nerve glioma, sphenoid wing dysplasia/thinning of long bone cortex, axillary or inguinal freckling, primary relative with NF1and multiple Lisch nodules.

The orbital disease is due to the involvement of the optic nerve, orbital bones, and eyeballs [4]. Unilateral involvement is commonly seen and is associated with ipsilateral extracranial disease, however, this patient showed the presence of PNF on contralateral side as well. Involvement of eyeball leads to enlargement of globe (buphthalmos), and glaucoma. Intraorbital tumors such as optic nerve glioma and PNF of the intraorbital nerves, optic nerve sheath, and sclera are seen.  Sphenoid wing dysplasia leads to pulsatile exophthalmos, and herniation of the middle cranial fossa content into orbit.  Retinal detachment is rare, however seen in this case.

The most common neurological symptom is cognitive disability [5]. Increased incidence of CNS tumors is seen namely juvenile pilocytic astrocytoma, diffuse brainstem glioma, spinal astrocytomas, and spinal pilocytic astrocytoma [6]. T2/FLAIR hyperintense focal areas of signal intensity (FASI) are also seen in the deep white matter, basal ganglia, and corpus callosum without any contrast enhancement.

Wilms tumor, pheochromocytoma, rhabdomyosarcoma, renal angiomyolipoma, and renal artery stenosis are also seen. Tumors and cardiovascular complications are the most common causes of mortality [7].

Bony orbital changes are suggested to be secondary to the interaction of developing skull with plexiform neurofibroma [4].

PNF and sphenoid wing dysplasia confirmed the clinical diagnosis of NF1.  Supportive treatment and palliative surgery were advised for facial disfigurement. The patient’s parents and siblings were advised genetic counseling. The patient was kept under surveillance for new manifestations. Prognosis is very variable depending upon the severity and the systemic involvement. However overall life expectancy is considerably lower.

This case highlights the implication of facial disfigurement and vision loss as an important social stigmata and morbidity in young patients of NF1 and the need of cosmetic/ plastic surgery in such patients.

Written informed patient consent for publication has been obtained.