Baroutis Konstantinos G, Hoyek Sandra, Correa Victor S M C, Ntentakis Dimitrios P, Patel Nimesh A, Vavvas Demetrios G
Department of Ophthalmology, Retina Service, Ines and Frederick Yeatts Lab in Retina Research, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
Eye (Lond). 2025 Sep 11. doi: 10.1038/s41433-025-03966-0.
BACKGROUND/OBJECTIVES: Cowden syndrome (CS) is a rare genetic disorder caused by mutations in the PTEN gene associated with multisystem hamartomas and predisposition to malignancies. Although ocular involvement has been reported in case studies, systematic data are lacking. This study aimed to evaluate the prevalence, characteristics, and genotypic associations of ocular manifestations in CS patients within a large tertiary healthcare system.
SUBJECTS/METHODS: We conducted a retrospective cohort study using the Mass General Brigham (MGB) Research Patient Data Registry, encompassing over 6 million patients from 2005 to 2024. Patients meeting clinical or genetic criteria for CS were identified. Ophthalmic findings, genotype-phenotype correlations, and clinical follow-up were extracted and analysed. A comprehensive literature review on CS-related ocular findings was performed to contextualize findings.
Of the 6,026,276 patients in the RPDR, 144 patients carried the diagnostic codes for CS. After a manual review of all charts, 77 met the clinical or genetic criteria for CS. Of these, 17 (22%) underwent ophthalmologic evaluation, and 4 (5%) exhibited CS-related ocular findings, including retinal hamartoma, eyelid hemangioma, trichilemmoma, and a peripapillary hamartoma-like lesion. Most patients maintained excellent vision over a median follow-up of four and a half years. Retinal imaging was limited, with OCT and OCTA available in only one case. Genotype analysis revealed that truncating PTEN variants were more likely associated with central nervous system involvement. Literature review identified a broader spectrum of ocular anomalies in CS, underscoring phenotypic variability.
The prevalence of CS in a large US tertiary setting is 1.28/100,000. Ocular manifestations in CS are rare and typically benign, with preserved vision in most cases. However, variability in presentation and mutation types may influence the risk. Notably, three of the four patients with ocular findings, possibly associated with CS, carried truncating variants. The fourth was PTEN-positive, but the specific variant was not retrievable. Multicentre studies are warranted to better define the full ocular phenotype of CS and to guide screening recommendations.
背景/目的：考登综合征（CS）是一种罕见的遗传性疾病，由PTEN基因突变引起，与多系统错构瘤和恶性肿瘤易感性相关。尽管在病例研究中已有眼部受累的报道，但缺乏系统性数据。本研究旨在评估大型三级医疗保健系统中CS患者眼部表现的患病率、特征和基因型关联。
受试者/方法：我们使用麻省总医院布莱根分院（MGB）研究患者数据登记处进行了一项回顾性队列研究，涵盖了2005年至2024年的600多万名患者。确定符合CS临床或基因标准的患者。提取并分析眼科检查结果、基因型-表型相关性和临床随访情况。对与CS相关的眼部检查结果进行了全面的文献综述，以将研究结果置于背景中。
在RPDR的6,026,276名患者中，144名患者有CS的诊断编码。在对所有病历进行人工审查后，77名患者符合CS的临床或基因标准。其中，17名（22%）接受了眼科评估，4名（5%）表现出与CS相关的眼部检查结果，包括视网膜错构瘤、眼睑血管瘤、毛发上皮瘤和视乳头周围错构瘤样病变。在中位随访四年半的时间里，大多数患者视力保持良好。视网膜成像有限，只有一例患者可进行光学相干断层扫描（OCT）和光学相干断层扫描血管造影（OCTA）检查。基因型分析显示，截短型PTEN变异更可能与中枢神经系统受累相关。文献综述发现CS患者存在更广泛的眼部异常，强调了表型变异性。
在美国大型三级医疗机构中，CS的患病率为1.28/10万。CS的眼部表现罕见且通常为良性，大多数情况下视力得以保留。然而，表现形式和突变类型的变异性可能会影响风险。值得注意的是，四名有眼部检查结果且可能与CS相关的患者中，有三名携带截短型变异。第四名患者PTEN呈阳性，但具体变异无法获取。有必要开展多中心研究，以更好地界定CS的完整眼部表型并指导筛查建议。
