An international research team has identified a previously unrecognized form of inherited retinal degeneration tied to a specific variant — p.Arg140Trp — in the EFEMP1 gene. The same gene was already known to cause Doyne honeycomb retinal dystrophy (Malattia Leventinese), but that condition stems from a different variant and attacks the central retina. This newly described disease does the opposite: it targets the peripheral retina and rod photoreceptors, which are responsible for low-light and night vision.

What makes this disease especially tricky to catch is that rod function can be severely compromised while the retina still looks completely normal on clinical exam. Patients may struggle with night vision and peripheral sight for years before any structural damage becomes visible — meaning the disease can fly under the radar for a long time.

Key Takeaways:

• Retinal dysfunction clearly precedes visible structural damage, offering a functional marker for early detection
• The p.Arg140Trp EFEMP1 protein abnormally accumulates inside cells and is less efficiently secreted — pointing to a distinct disease mechanism
• The newly described condition shares features with rare disorders like gyrate atrophy and choroideremia, and may account for genetically unresolved inherited eye diseases

Why it matters: This discovery expands the known disease spectrum of EFEMP1 and highlights that the same gene can produce fundamentally different retinal diseases depending on the variant. For clinicians, it underscores the importance of functional testing even when the retina appears structurally intact — and opens a new avenue for diagnosing patients who have long lacked a genetic explanation for their vision loss.