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Ophthalmological manifestations in a cohort of Cowden syndrome patients in a large tertiary healthcare system

Eye volume 39, pages 2926–2932 (2025)Cite this article

Subjects

Abstract

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.

Results

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.

Conclusions

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.

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Fig. 1: Multimodal imaging and histopathological findings in two ophthalmic cases.

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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The study is funded by Yeatts and Loeffler Family funds.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Retina Service, Ines and Frederick Yeatts Lab in Retina Research, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA

    Konstantinos G. Baroutis, Sandra Hoyek, Victor S. M. C. Correa, Dimitrios P. Ntentakis, Nimesh A. Patel & Demetrios G. Vavvas

Authors
  1. Konstantinos G. Baroutis
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  2. Sandra Hoyek
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  3. Victor S. M. C. Correa
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  4. Dimitrios P. Ntentakis
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  5. Nimesh A. Patel
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  6. Demetrios G. Vavvas
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Contributions

K.G. Baroutis: Collected and analyzed the data, validated the study and drafted the manuscript. S. Hoyek: Validated the data and contributed to manuscript revisions. V.S.M.C. Correa: Validated the data and contributed to manuscript revisions. D.P. Ntentakis: Validated the data and contributed to manuscript revisions. N.A. Patel: Validated the data and contributed to manuscript revisions. D.G. Vavvas: Supervised the project, provided guidance, and approved the manuscript.

Corresponding author

Correspondence to Demetrios G. Vavvas.

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Baroutis, K.G., Hoyek, S., Correa, V.S.M.C. et al. Ophthalmological manifestations in a cohort of Cowden syndrome patients in a large tertiary healthcare system. Eye 39, 2926–2932 (2025). https://doi.org/10.1038/s41433-025-03966-0

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