Overview
Enhanced S-Cone Syndrome (ESCS), also known as Goldmann-Favre syndrome in its severe form, is a rare autosomal recessive retinal dystrophy caused by mutations in NR2E3. It is characterized by an abnormal overabundance of short-wavelength (blue/S-cone) photoreceptors at the expense of rod and long/medium-wavelength cones. Patients experience night blindness, retinoschisis-like changes, and progressive visual loss from childhood.
Genetics
ESCS is caused exclusively by mutations in NR2E3, a nuclear receptor gene critical for rod photoreceptor differentiation. Inheritance is autosomal recessive.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| NR2E3 | 15q23 | AR | Nuclear receptor subfamily 2 group E member 3; sole known cause of ESCS |
Clinical Presentation
Childhood
- Night blindness (nyctalopia)
- Reduced visual acuity
- Nystagmus in some cases
Progressive
- Retinoschisis-like macular changes
- Pigmentary retinopathy
- Vitreous degeneration (Goldmann-Favre)
Advanced
- Severe visual field loss
- Legal blindness in many patients
- Cataract formation
Diagnosis
- ERG: Pathognomonic — enhanced S-cone response with absent rod response
- Fundus: Pigmentary changes, retinoschisis, vitreous veils (in Goldmann-Favre)
- OCT: Intraretinal cysts, schisis cavities
- Genetic testing: NR2E3 sequencing
Current Research & Treatment
No approved treatments exist. NR2E3 gene therapy is in preclinical development. The overlap with NR2E3-associated RP (clumped pigmentary RP) has led to shared research pathways. Neuroprotective strategies are being explored.
Active Clinical Trials
The following active clinical trials are investigating treatments for Enhanced S-Cone Syndrome. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.