Birt-Hogg-Dubé syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature

ABSTRACT

Purpose

To report a rare case of Birt-Hogg-Dubé Syndrome (BHD) with progressive chorioretinopathy.

Methods

Case report.

Results

A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy.

Conclusion

BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities.

Abbreviations

BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.

KEYWORDS:

• Birt-Hogg-Dubé syndrome (BHD)
• retinal pigment epithelium
• renal cell carcinoma
• dark adaptation
• electroretinogram

Acknowledgments

The authors would like to thank Dr Greg Blaha, Dr Shiyoung Roh, Dr Michael Lewen, Dr Megan Nicholas, Dr Haohua Qian, as well as Carol Spencer, Lahey Hospital Librarian, for research support. D.J. Ramsey is the Harry N. Lee Family Chair in Innovation at the Lahey Hospital & Medical Center, Beth Israel Lahey Health.

Authors’ contributions

EKK was responsible for the chart review, extracting and analyzing the data, figure development, and writing the manuscript. NS was responsible for chart review, interpreting the data, and writing the manuscript. DJR was responsible for the study, collecting and analyzing the data, interpreting the results, and writing the manuscript. All authors read and approved the final manuscript.

Availability of data and materials

All data generated or analyzed during this study are included in this manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Ethics approval and consent to participate

Written informed consent for case report publication was received from the patient.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

D.J.R. is supported by the Myles and Gertrude Hanson Foundation, Providence, Rhode Island, and by the Harry N. Lee Family Chair in Innovation, Lahey Hospital & Medical Center, Beth Israel Lahey Health, Peabody, Massachusetts.