Proteus Syndrome: Report of a Case with Developmental Glaucoma

Article information

Korean J Ophthalmol. 2014;28(3):272-274

Publication date (electronic) : 2014 May 19

doi : https://doi.org/10.3341/kjo.2014.28.3.272

Zuleyha Sik Sarman ¹, Nursen Yuksel ¹, Hakan Sarman ², Dilek Bayramgurler ³

¹Department of Ophthalmology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.

²Department of Orthopaedics and Traumatology, Abant Izzet Baysal University Faculty of Medicine, Bolu, Turkey.

³Department of Dermatology and Venereology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.

Corresponding Author: Zuleyha Sik Sarman, MD. Department of Ophthalmology, Kocaeli University Faculty of Medicine, Kocaeli 41180, Turkey. Tel: 90-555-5481060, Fax: 90-262-3037003, zuleyhasarman@gmail.com

Received 2013 December 23; Accepted 2014 April 02.

Abstract

The purpose of this study was to report developmental glaucoma and pseudopapilledema in a patient with Proteus syndrome. We defined the presence of developmental glaucoma, right pseudopapilledema and myopia in a 4.5-year-old patient with Proteus syndrome. Marked right hemihypertrophy, lipoma, macrodactyly, and asymmetry of the limbs were observed on systemic examination. A cavernoma was also detected in magnetic resonance imaging of the brain. The patient underwent bilateral goniotomy surgery due to glaucoma. The surgical outcomes were satisfactory in both eyes. In conclusions developmental glaucoma and pseudopapilledema might be associated with Proteus syndrome.

Keywords: Developmental glaucoma; Proteus syndrome; Pseudopapilledema

Proteus syndrome (PS) was first described as a clinical entity by Cohen and Hayden [1] in two patients in 1979. Dietrich et al. [2] titled the disease, which has multiple, diverse, somatic manifestations, as the Greek god Proteus, who could change his form at will. PS is a complex hamartomatous disorder involving the skeletal system, skin, soft tissues, and vascular system. PS is an exceptionally rare and overdiagnosed disorder of mosaic growth dysregulatıon [3,4]. The characteristic signs include partial gigantism of the hands a nd/or f eet, a symmetry of the limbs, plantar hyperplasia, macrodactyly, bony exostoses, soft tissue tumors (hemangioma, lymphangioma, lipoma), varicosities, mental retardation, bony prominences on the skull, scoliosis, kyphosis, angulation knee defects, muscle atrophy, pelvic lipomatosis, verrucous epidermal nevi, and long bone overgrowth [3,4,5,6].

About 200 cases of PS have been reported in the literature, and incidence of ocular malformations is unknown [3]. Fibrous tumor of the superior oblique tendon [7], retinal dysgenesis, retinal pigmentary abnormalities, optic nerve hypoplasia, strabismus and high myopia [3], calcific band keratopathy, cataract, vitreous hemorrhage and resolved serous retinal detachment [8], epibulbar tumor, posterior segment hamartoma, enlarged eye [9,10], and glaucoma [6,10,11] characterize the syndrome. However the ocular manifestations of PS require clarification.

We report herein a patient with developmental glaucoma and pseudopapilledema, presumed to be due to PS.

Case Report

A 4.5-year-old male was referred to our ophthalmology department, due to developmental glaucoma. The prenatal history was unremarkable. On physical examination, marked right hemihypertrophy, a protuberant abdomen containing subcutaneous tumors and lipoma, macrodactyly of the third and fourth digits of the right hand, macrodactyly in nearly all of the toes (Fig. 1), hyperpigmented skin lesions on his back and legs, verrucous epidermal nevi, and asymmetry of the limbs were discovered. Magnetic resonance imaging of the brain showed a temporal lobe cavernoma (Fig. 2). However, there were no neurological symptoms related with the cavernoma.

Fig. 1

(A) Right hemihypertrophy, (B) subcutaneous tumors and lipoma, (C) macrodactyly of the third and fourth digits of the right hand, and (D) macrodactyly of nearly all the toes.

Fig. 2

Magnetic resonance imaging of the case, showing temporal lobe cavernoma.

On ophthalmic examination, bilateral developmental glaucoma, unilateral pseudopapilledema, and myopia were detected. The patient had a history of a bilateral goniotomy operation when he was four months old. Visual acuity could not be measured due to mental-motor retardation, but central, steady, maintained fixation (CSM) was positive in both eyes. Slit-lamp examination showed Haab's Striae with a corneal diameter of 11 mm horizontally and 12 mm vertically in the right eye. The left eye was buphthalmic, with a corneal diameter of 12 mm horizontally and 13 mm vertically. Gonioscopy showed grade 4 open angles in both eyes. Intraocular pressures were 12 mmHg in the right eye and 14 mmHg in the left eye with latanoprost 0.005% once a day treatment. Central corneal thickness measurements using ultrasonic pachymetry were 557 µm in the right eye and 509 µm in the left eye. Pseudopapilledema was also detected in the right eye. Cup/disc ratio was 0.5 in the right eye and 0.7 in the left eye (Fig. 3). Axial lengths were 22.8 mm in the right eye, and 25.36 mm in the left eye. Cycloplegic retinoscopy showed -5.50 (-2.50 × 90) diopters in both eyes. Best-corrected visual acuity was 20 / 40 in the right eye and 20 / 50 in the left eye.

Fig. 3

(A) Buphthalmia in the left eye, (B) pseudopapilledema in the right eye, and (C) appearance of left optic disc.

Discussion

PS is thought to occur as the result of a lethal somatic gene mutation that leads to a mosaic state. Most patients with PS are born without significant asymmetry, but some cases were diagnosed using prenatal ultrasonography, and rapidly progressive overgrowth could paused during puberty [7,10,11,12,13,14]. The most common clinical ocular manifestations of the disease have been reported to be strabismus and epibulbar tumors [10,11,12]. In the present case report, we defined a concordance of developmental glaucoma, pseudopapilledema, and myopia in a 4.5-year-old male patient with PS.

Clinical diagnosis of PS is challenging and contentious. In the early stages of the disease, it may be difficult to make differential diagnosis from other overgrowth disorders, such as neurofibromatosis, Klippel-Trenaunay-Weber syndrome, Maffucci syndrome, Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi (CLOVE) syndrome, and Bannayan syndrome. These disorders may present with similar manifestations as PS; however, they had stringent diagnostic criteria that delineated a distinct cohort of patients who have parallel features of overgrowth [4,13,14]. According to the literature; the prognosis of the PS seems to labile and is correlated to the severity of neurological involvement, skeletal deformities, internal lipomatosis, and neoplastic appearance [8]. Different manifestations suggest that patients with PS should have an ophthalmological examination.

We have defined in the present report that developmental glaucoma and pseudopapileudema in a patient with PS for the first time in the literature. The diagnosis of PS was based on the typical clinical findings including hemihypertrophy, subcutaneous tumors and lipoma, macrodactyly, hyperpigmented skin lesions, verrucous epidermal nevi, and asymmetry of the limbs. Ophthalmologic examination revealed developmental glaucoma which was already treated with goniotomy in both eyes. Although the intraocular pressures were in normal limits with latanoprost 0.005% once a day treatment, left eye enlargement was evident. Although the precise mechanism of the pathogenesis of secondary glaucoma associated with PS is unknown, the most likely explanation is the malformation of the trabecular meshwork and iris (iridotrabeculodysgenesis) or iridocorneal dysgenesis. Hamarthomatous lesions may also be another cause of glaucoma in these individuals.

In conclusion, patients with a diagnosis of PS should be carefully reviewed by an ophthalmologist to rule out ocular manifestations of the disease. Timely diagnosis and treatment of the developmental glaucoma may preserve visual loss in patients with PS.

Notes

No potential conflict of interest relevant to this article was reported.

References

1. Cohen MM Jr, Hayden PW. A newly recognized hamartomatous syndrome. Birth Defects Orig Artic Ser 1979;15:291–296. 118782.

2. Dietrich RB, Glidden DE, Roth GM, et al. The Proteus syndrome: CNS manifestations. AJNR Am J Neuroradiol 1998;19:987–990. 9613526.

3. Sanchez-Lopez M, Martinez-Fernandez R, Santamaria-Carro A. Ocular manifestations in Proteus syndrome. Arch Soc Esp Oftalmol 2007;82:175–178. 17357896.

4. Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet 2006;14:1151–1157. 16883308.

5. Gilbert-Barness E, Cohen MM Jr, Opitz JM. Multiple meningiomas, craniofacial hyperostosis and retinal abnormalities in Proteus syndrome. Am J Med Genet 2000;93:234–240. 10925389.

6. Rizzo R, Pavone L, Sorge G, et al. Proteus syndrome: report of a case with severe brain impairment and fatal course. J Med Genet 1990;27:399–402. 2359106.

7. Trivedi D, Lee SY, Brundler MA, Parulekar MV. Fibrous tumor of the superior oblique tendon in Proteus syndrome. J AAPOS 2013;17(4):420–422. 23896365.

8. Sheard RM, Pope FM, Snead MP. A novel ophthalmic presentation of the Proteus syndrome. Ophthalmology 2002;109:1192–1195. 12045066.

9. Venugopalan P, Joshi SN, Koul RL, et al. Proteus syndrome: a variant with eye involvement. Eye (Lond) 2001;15(Pt 1):116–118. 11318277.

10. De Becker I, Gajda DJ, Gilbert-Barness E, Cohen MM Jr. Ocular manifestations in Proteus syndrome. Am J Med Genet 2000;92:350–352. 10861666.

11. Mayatepek E, Kurczynski TW, Ruppert ES, et al. Expanding the phenotype of the Proteus syndrome: a severely affected patient with new findings. Am J Med Genet 1989;32:402–406. 2729359.

12. Burke JP, Bowell R, O'Doherty N. Proteus syndrome: ocular complications. J Pediatr Ophthalmol Strabismus 1988;25:99–102. 3282059.

13. Viljoen DL, Nelson MM, de Jong G, Beighton P. Proteus syndrome in southern Africa: natural history and clinical manifestations in six individuals. Am J Med Genet 1987;27:87–97. 3605209.

14. Bouzas EA, Krasnewich D, Koutroumanidis M, et al. Ophthalmologic examination in the diagnosis of Proteus syndrome. Ophthalmology 1993;100:334–338. 8460002.

Article information Continued

(open-access, http://creativecommons.org/licenses/by-nc/3.0/) :

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.