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E. Schneider, J. Eisengart, C. Eng, S. Moroi; Ophthalmic Phenotypes in Cowden Syndrome Associated With Germline PTEN Mutations. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3095.
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To characterize ocular phenotypes in patients with Cowden syndrome (CS) associated with mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN). CS is an autosomal dominant, hamartomatous disorder involving all three embryonic layers and linked to an increased risk of breast, thyroid, and endometrial malignancies.
Medical records were reviewed and PTEN genetic analysis performed on three subjects enrolled in an approved IRBMED protocol. Additional ocular phenotypes described in CS were reviewed in published reports of cases diagnosed by clinical criteria or PTEN genotyping.
Case 1 presented with bilateral posterior uveitis, which was complicated by marked proliferative inflammation leading to tractional retinal detachment OU treated by pars plana vitrectomy OU. She developed cataracts OU and glaucoma OD treated medically and later by Baerveldt implant, which quickly encapsulated and was managed by surgical excision. Case 2 presented with narrow angles and elevated IOP managed by laser iridotomy OU. Case 3 presented with exposure keratopathy due to facial nerve palsy related to the presence of a cerebellar gangliocytoma, a pathognomonic finding in CS. Genotyping revealed single base substitutions at conserved splice sites in exons 3 and 8 in cases 1 and 2, respectively and a single base deletion in exon 9 in case 3. Literature review revealed 37 cases with reported ocular findings including periocular cutaneous hamartomas, retinal harmatomas, posterior uveitis and pre-senile cataracts.
Among reviewed cases, Case 1 demonstrated a propensity towards gliotic and fibrotic proliferation, which may be related to loss of the anti-proliferative effects of PTEN and consistent with previous reports of retinal harmatomas and uveitis. Future studies to systematically characterize the potential ophthalmic manifestations of CS are underway. Given the increased risk of breast, thyroid, and endometrial malignancy, ophthalmic recognition of characteristic ocular phenotypes in CS will allow for timelier referral for genetic testing and cancer surveillance.
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