The blue rubber bleb nevus syndrome (BRBNS) is a rare disorder consisting of cutaneous and visceral (particularly gastrointestinal) hemangiomas, the latter frequently associated with severe bleeding.1,2 Ocular involvement is rare.3,4 We report herein a case of childhood-onset BRBNS with eyelid, conjunctival, choroidal, and orbital lesions.
A 9-year-old Caucasian girl with a histopathologic diagnosis of BRBNS was referred for examination because of headaches. She had 28 prior hospital admissions for complications arising from BRBNS, including gastrointestinal bleeding and surgery for intestinal, hepatic, and foot lesions. She had been tutored at home and had never undergone vision screening. She was the only known affected member of her family. Her mother's and father's ages at her birth were 25 and 27, respectively.
The patient was small; her weight (17.7 kg) and height (118 cm) were below the fifth percentile for her age. Snellen visual acuity without correction was 20/80 OD and 20/30 OS. Pupillary responses were normal. Motility examination revealed a 20 prism diopter esophoria with normal auctions and versions. Blue, nontender, rubbery, compressible hemangiomas were seen on the trunk and extremities (Fig 1). A diffuse bluish lesion on her right upper cheek involved her lower eyelid, but did not affect lid contour or obstruct the pupillary axis.
Slit-lamp examination revealed a hemangioma on the lid margin and tarsal conjunctiva OS (Fig 2). Ophthalmoscopy revealed a slightly elevated gray choroidal lesion under the macula OD with overlying pigment epithelial changes (Fig 3). The optic disks were crowded bilaterally with small physiologic cups. Cycloplegic retinoscopy resulted in a refraction of +4.50+1.00x105 OD and +4.00+0.25x75, OS but this did not improve her visual acuity; the etiology of her decreased vision OS was unclear. The remainder of the examination was unremarkable.
Ultrasonography revealed bilateral echodense lesions beneath the surface of the optic disks that were interpreted as buried disk drusen and a small dome-shaped macular lesion OD (Fig 4). Fluorescein angiography was deferred due to poor patient cooperation.
Fig 1: Skin lesions of the patient's blue rubber bleb nevus syndrome.
Fig 2: Conjunctival and lid margin hemangioma OS of the patient.
Review of a screening computerized tomography (CT) scan of the head performed 6 months prior to our examination showed contrast-enhancing lesions in both orbits intraconally (Fig 5) as well as a left vertex nodule with minimal mass effect and focal dilatation of the right lateral ventricle. The CT scan sections did not include the optic nerve or macula, and no other intraocular calcifications were seen. No further imaging studies were performed. Six months later, the patient's ophthalmic findings were unchanged.
Fig 3: Elevated choroidal lesion beneath the macula OD.
Bean reintroduced Gascoyen's syndrome of cutaneous and gastrointestinal vascular malformations to the medical literature and gave it the descriptive name of BRBNS.1 The syndrome generally manifests in childhood, although adultonset cases are known.5 Dominant inheritance has been described, although many cases are isolated. Recently, a gene for venous malformations was mapped to chromosome 9p from an extended family in which several members had BRBNS-like cutaneous, mucocutaneous, and visceral lesions.6 The gene for BRBNS has not been definitively mapped.
Few previous cases document ophthalmic involvement in BRBNS. One neonate had cavernous hemangiomas in the bulbar conjunctiva, iris, and retina; all lesions regressed spontaneously within 7 months.3 A large defect in the retinal pigment epithelium was noted at the site of the retinal hemangioma after it had regressed.
A review of previous BRBNS literature revealed two additional cases, one with an iris lesion OD who was blind from bilateral occipital pole lesions and one with fundus lesions that regressed by 28 months.7 Gass reviewed retinal cavernous hemangiomas in several patients who may have had BRBNS based on his description of their cutaneous lesions.8 One elderly patient with late-onset BRBNS had an orbital vascular malformation that caused self-limited intermittent exophthalmos.4
The patient we describe had multiple lesions involving the eyelids, conjunctiva, and orbit, but her decreased visual acuity OD probably is associated with her submacular choroidal lesion.
Choroidal hemangiomas are of two types: diffuse, which usually are associated with Sturge-Weber syndrome; and circumscribed, which are rare, usually solitary tumors found in patients without other vascular malformations. Circumscribed hemangiomas rarely are detected before the third decade of life; they usually are diagnosed in middle or later life when symptoms result from degeneration of the overlying pigment epithelium and retina or serous retinal detachment.9
Fig 4: Ultrasonography OD (through closed eyelid) showing (top) buried disk drusen and (bottom) submacular lesion.
A review of the literature on circumscribed choroidal hemangiomas did not reveal any cases associated with cutaneous, visceral, or central nervous system hemangiomas.
Our patient presented with poor vision OD due to a submacular lesion that did not have the distinct orange-red, markedly elevated appearance of a typical circumscribed choroidal hemangioma, but given the posterior location of the lesion10 and the previously documented propensity of intraocular BRBNS-associated lesions to regress,37 we believe this lesion may represent an atypical, possibly regressed, choroidal hemangioma.
We recommend ophthalmic screening of patients with BRBNS in early childhood whenever possible.
Fig 5: (Left) Computed tomography of the head demonstrates intraconal lesions that enhance (right) after administration of intravenous contrast. (Images are at slightly different levels due to patient orientation during scanning.)
1. Bean WB. Vascular Spiders and Related Lesions of the Skin. Springfield, DJ: Charles C. Thomas; 1958:178-185.
2. Moodey M, Ramdial P. Blue rubber bleb nevus syndrome: case report and review of the literature. Pediatrics. 1993;3:160-162.
3. Crompton JL, Taylor D. Ocular lesions in the blue rubber bleb naevus syndrome. Br J Ophthalmol. 1981;65:133-137.
4. Rennie IG, Shortland JR, Mahood JM, Browne BH. Periodic exophthalmos associated with the blue rubber bleb naevus syndrome: a case report. Br J Ophthalmol. 1982;66:594-599.
5. Paules S, Baack B, Levisohn D. Tender bluish papules on the trunk and extremities: blue rubber-bleb nevus syndrome. Arch Dermatology. 1993;129:1505-1506,1508-1509.
6. Gallione CJ, Pasyk KA, Boon LM, et al. A gene for familial venous malformations maps to chromosome 9p in a second large kindred. J Med Genet. 1995;32:197-199.
7. Burke EC, Winkelman RK, Strickland MK Disseminated hemangiomatosis. American Journal of Diseases in Children. 1964;108:418424.
8. Gass JDM. Cavernous hemangioma of the retina- a neuro-oculocutaneous syndrome. Am J Ophthalmol. 1971;71:799-814.
9. Gass JDM. Stereoscopic Atlas of Macular Diseases, 3rd ed. St Louis, Mo: CV. Mosby; 1987:172-177.
10. Shields JA, Shields CL. Intraocular Tumors: A Text and Atlas. Philadelphia, Pa: W.B. Saunders; 1992:240-252.