From the 1st Department of Ophthalmology (NGZ, EDK, KGB), Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki; and the Department of Ophthalmology (EDK), General Hospital of Veria, Veria, Greece.
Presented at the European Pediatric Ophthalmology Society annual meeting; October 23–25, 2008; Leuven, Belgium.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Evgenia D. Kanonidou, MD, PhD, 97 Vlasi Gavriilidi Street, GR55131 Kalamaria, Thessaloniki, Greece. E-mail: firstname.lastname@example.org
Neurofibromatosis type 1 (NF-1) or von Recklinghausen disease is an autosomal dominant phakomatosis inherited with a frequency of 1 in 3,000 to 4,000 live births.1 The incidence of head and neck involvement ranges from 1% to 22% in published literature and affects both males and females with the same prevalence and severity.1,2 NF-1 is diagnosed by at least two of the following: (1) six or more café-au-lait macules, (2) two or more axillary or inguinal freckles, (3) two or more Lisch nodules (iris hamartomas), (4) two or more neurofibromas or one plexiform neurofibroma, (5) bone dysplasia, (6) optic glioma, or (7) first-degree relative with NF-1. These criteria established by the National Institutes of Health (NIH) are highly applicable for diagnosing adults as having NF-1, whereas pediatric patients might not meet the criteria on initial presentation. Many of the presenting signs increase in incidence during childhood and puberty, rendering the diagnosis of NF-1 more apparent as the patient ages.3 Orbital lesions seen in NF-1 include unilateral buphthalmos (congenital glaucoma), plexiform neurofibromas, osseous dysplasia of the orbit, and neoplasms such as optic gliomas, perioptic meningiomas, neurofibromas, and schwannomas. The exact relationship of congenital glaucoma to NF-1 remains uncertain.
We present the diagnostic challenge of an unusual case of NF-1 with unilateral congenital glaucoma, buphthalmos, and sphenoid-orbital dysplasia. The accompanying type of osseous orbital dysplasia has rarely been described in the literature, complicating the diagnostic and management process.
A 6-month-old boy presented with right buphthalmos since birth. Examination under anesthesia confirmed the diagnosis of unilateral congenital glaucoma with right corneal opacities accompanied with Descemet’s membrane splits. The corneal diameters were 12.5 mm in the right eye and 10 mm in the left eye. Intraocular pressures, measured with Perkins tonometer, were 31 mm Hg in the right eye and 10 mm Hg in the left eye, and the axial length was 27.80 and 20.20 mm, respectively. The right cup-to-disc ratio was equivalent to 0.95 and the left was 0.2. Finally, the right pupil was not reactive and ectropion uvea was noted. No other abnormalities were detected. Because of difficult visibility, a trabeculectomy with mitomycin C was performed. At the age of 2 years, he developed a right upper eyelid lesion with associated mild ptosis and ipsilateral facial hemihypertrophy (Fig. 1). Also, more than six café-au-lait spots over 5 mm in greatest diameter were detected in the trunk. Biopsy of the eyelid lesion confirmed the presence of plexiform neurofibroma arising from the trigeminal nerve.
Figure 1. Right periocular dysplasia with orbital content prolapse and “S”-shaped upper eyelid ptosis due to the plexiform neurofibroma, which is most prominent on the supralateral orbital area.
The diagnosis of NF-1 was reached based on the NIH diagnostic criteria. There was no positive family history and systemic evaluation by the pediatricians was unremarkable. The computed tomography scan of the brain and orbits revealed a distinctive but uncommon type of ipsilateral sphenoid-orbital dysplasia that was consistent with the manifestations of the disease.4–6 More precisely, hypoplasia of the minor and major wing of the sphenoid bone associated with extensive loss of the posterior orbital wall and enlargement of the pterygoid fossa with moderate expansion of the middle cranial fossa into the posterior orbit were detected. The greater wing of the sphenoid was partially decalcified and bowed forward, with an equivocal arachnoid cyst. There was evidence of right optic canal enlargement due to tumor infiltration of the optic nerve sheath without an optic nerve glioma (Fig. 2).
Figure 2. (A) Axial T1-weighted magnetic resonance image showing forward bowing of the right temporal lobe, tumor infiltration of the optic nerve sheath without an optic nerve glioma, protrusion of cranial content trough an enlarged optic canal, and possible arachnoid cyst formation. The ipsilateral globe is buphthalmic. (B) Axial computed tomography scan shows absence of the greater wing of the sphenoid on the right orbit, allowing the temporal lobe to partially prolapse through the enlarged superior orbital fissure.
NF-1 in children is diagnosed by the presence of two or more cardinal clinical features included in the diagnostic criteria established by the NIH. Although this systematic approach is the mainstay for diagnosis by the age of 8 years, modification of these criteria might be essential to provide a more accurate and prompt diagnosis in younger children younger than 8 years.2 Our case had multiple typical NF-1 features, such as six or more café-au lait macules over 5 mm in greatest diameter, one plexiform neurofibroma, and a distinctive osseous lesion that according to the NIH criteria confirm a reliable diagnosis. However, our patient was initially diagnosed as having congenital glaucoma and treated accordingly because he did not meet the diagnostic signs at presentation. The eyelid and orbital neurofibromas started manifesting at the age of 2 years and the diagnosis of orbitotemporal neurofibromatosis was established at a later stage following the completion of the necessary imaging investigation. More specifically, the presenting feature of right buphthalmos at the age of 6 months indicated the presence of congenital glaucoma. The café au-lait spots and plexiform neurofibromas of the upper eyelid suggested the presence of NF-1. The complete diagnosis of childhood orbitotemporal neurofibromatosis was established following the identification of the sphenoid-orbital dysplasia with the imaging examination at a later age.
Only 20 cases of infants with neurofibromatosis and congenital glaucoma have been reported in the English literature.7 Buphthalmos was detected at birth in all but one and in every case preceded the appearance of café-au-lait spots or any other clinical signs of neurofibromatosis. Eight of the cases had a plexiform neurofibroma of the upper eyelid, 3 had ipsilateral facial hypertrophy, and 6 had a family history suggestive of NF-1. However, pterygoid-orbital dysplasia was described in none of these cases. These characteristic osseous lesions are usually apparent within the first year of life and occur in 14% of patients with NF-1.2 Our case demonstrates the rare association between unilateral congenital glaucoma and orbitotemporal NF-1.
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- DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics. 2000;105:608–614. doi:10.1542/peds.105.3.608 [CrossRef]
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- Jacquemin C, Bosley TM, Liu D, Svedberg H, Buhaliqa A. Reassessment of sphenoid dysplasia associated with neurofibromatosis type 1. Am J Neuroradiol. 2002;23:644–648.
- Reed D, Robertson WD, Rootman J, Douglas G. Plexiform neurofibromatosis of the orbit: CT evaluation. Am J Neuroradiol. 1986;7:259–263.
- Payne MS, Nadell JM, Lacassie Y, Tilton AH. Congenital glaucoma and neurofibromatosis in a monozygotic twin: case report and review of the literature. J Child Neurol. 2003;18:504–508. doi:10.1177/08830738030180071101 [CrossRef]