Phenotypic expansion of retinal abnormalities in folliculin (FLCN) variant-related pathology (Birt-Hogg-Dubé syndrome).
| Title: | Phenotypic expansion of retinal abnormalities in folliculin (FLCN) variant-related pathology (Birt-Hogg-Dubé syndrome). |
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| Authors: | August AH; Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.; Department of Translational Ophthalmology, Wills Eye Hospital, Philadelphia, PA, USA.; Department of Pathology, Wills Eye Hospital, Philadelphia, PA, USA.; Shields CL; Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.; Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA.; Francis JH; Ophthalmic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Ophthalmology, Weill Cornell Medical Center, New York, NY, USA.; Chen FK; Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia.; Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.; Ocular Tissue Engineering Laboratory, Lions Eye Instititute, Nedlands, WA, Australia.; Pulido JS; Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.; Department of Translational Ophthalmology, Wills Eye Hospital, Philadelphia, PA, USA.; Retina Service, Wills Eye Hospital and Mid Atlantic Retina, Philadelphia, PA, USA. |
| Source: | Ophthalmic genetics [Ophthalmic Genet] 2026 Apr; Vol. 47 (2), pp. 137-146. Date of Electronic Publication: 2025 Nov 25. |
| Publication Type: | Journal Article; Case Reports; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 9436057 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-5094 (Electronic) Linking ISSN: 13816810 NLM ISO Abbreviation: Ophthalmic Genet Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Informa Healthcare; Original Publication: Buren, The Netherlands : Aeolus Press, c1994- |
| MeSH Terms: | Birt-Hogg-Dube Syndrome*/genetics ; Birt-Hogg-Dube Syndrome*/pathology ; Birt-Hogg-Dube Syndrome*/diagnosis ; Tumor Suppressor Proteins*/genetics ; Proto-Oncogene Proteins*/genetics ; Retinal Diseases*/genetics ; Retinal Diseases*/pathology ; Mutation* ; Retina*; Humans ; Retrospective Studies ; Male ; Female ; Tomography, Optical Coherence ; Phenotype ; Fluorescein Angiography ; Adult ; Middle Aged |
| Abstract: | Purpose: Birt-Hogg-Dubé (BHD) syndrome 1 is caused by pathogenic folliculin (FLCN) variants, resulting in classic hair follicle tumors, pulmonary cysts, pneumothorax, and renal cancer. FLCN is expressed in retinal tissues, and previous reports of BHD described flecked chorioretinopathy, choroidal melanoma, chorioretinal atrophy, and retinal pigment epithelium microdetachments. FLCN has been implicated in numerous cellular processes of metabolism, autophagy, differentiation, ciliary function, and cellular adhesion.; Methods and Findings: We performed a retrospective chart review of clinical information and imaging of patients with BHD from three centers and describe three patients who were found to have diffuse, abnormal, pinpoint foci observed across multiple retinal imaging modalities in both eyes (n = 6 eyes). These lesions were hypo- and hyperautofluorescent on fundus autofluorescence (FAF) and hypo- and hyperfluorescent on fluorescein angiography. Optical coherence tomography (OCT) revealed loss of inner retinal laminations, and numerous pinpoint hyperreflective lesions throughout the inner, middle, and outer retina which were seen in foveal, perifoveal, and peripheral retinal sections.; Conclusions: Mild retinal disorganization across multiple imaging modalities expands the ocular phenotype of BHD and likely arises from defects in cellular adhesion mediated by FLCN. Larger cohorts of patients with BHD may be necessary to establish these ocular imaging abnormalities as part of the BHD phenotypic spectrum. |
| Contributed Indexing: | Keywords: Birt–Hogg–Dubé syndrome; FLCN (folliculin); diabetic retinopathy; inherited retinal dystrophy; uveal melanoma; Local Abstract: [plain-language-summary] Retinal imaging of asymptomatic eyes in Birt–Hogg–Dubé syndrome was associated with diffuse low-grade retinal disorganization across multiple imaging modalities. These abnormalities may result from defects in folliculin-mediated cellular adhesion. |
| Substance Nomenclature: | 0 (FLCN protein, human); 0 (Tumor Suppressor Proteins); 0 (Proto-Oncogene Proteins) |
| Entry Date(s): | Date Created: 20251125 Date Completed: 20260325 Latest Revision: 20260519 |
| Update Code: | 20260520 |
| DOI: | 10.1080/13816810.2025.2590163 |
| PMID: | 41290560 |
| Database: | MEDLINE |
Journal Article; Case Reports; Multicenter Study