Giant macular hole in a female patient with X-linked Alport syndrome harboring a novel de novo COL4A5 variant.

PURPOSE: To report a female patient with genetically confirmed X-linked Alport syndrome (AS) presenting with progressive retinal thinning and giant macular hole formation.

METHODS

A 28-year-old woman with a history of bilateral LASIK surgery was referred for evaluation of bilateral progressive maculopathy. Comprehensive ophthalmic examinations, including optical coherence tomography (OCT) and full-field and multifocal electroretinography (ERG), were performed. Targeted next-generation sequencing of COL4A3, COL4A4, and COL4A5 genes was performed.

RESULTS

At presentation, decimal best-corrected visual acuity (BCVA) was 0.7 in the right eye (OD) and 1.2 in the left eye (OS). The patient had no hearing loss or family history of renal or ocular disease. OCT revealed bilateral retinal thinning. During follow-up, progressive thinning of all retinal layers was observed, and a macular hole developed in OS, gradually enlarging from 546 µm at age 34 to a giant macular hole measuring 1684 µm in minimum diameter at age 39. At 37 years of age, full-field ERG demonstrated preserved rod system function with mild cone system dysfunction, and multifocal ERG showed significantly reduced macular responses bilaterally. Genetic testing identified a novel de novo heterozygous COL4A5 variant (p.Gly775Val), classified as pathogenic, confirming X-linked AS.

CONCLUSIONS

X-linked AS may present with progressive diffuse macular thinning and giant macular hole formation even in female patients without hearing loss or a family history. AS should be considered in the differential diagnosis of unexplained bilateral macular thinning and giant macular hole in women.