Overview
Norrie disease is a rare X-linked recessive disorder caused by mutations in NDP (encoding Norrin), characterized by bilateral congenital blindness due to retinal dysplasia, pseudoglioma, and vitreoretinal malformation. Progressive sensorineural hearing loss develops in ~30% of patients in the second or third decade, and intellectual disability or psychotic features occur in a subset. It is allelic with X-linked FEVR and X-linked exudative vitreoretinopathy.
Genetics
Caused exclusively by NDP mutations. Norrin activates Wnt/β-catenin signaling critical for retinal and cochlear vascular development. X-linked recessive.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| NDP | Xp11.3 | X-linked | Norrin; sole cause; allelic with X-linked FEVR |
Clinical Presentation
Congenital
- Bilateral blindness at birth
- Leukocoria (white pupillary reflex)
- Retinal dysplasia and pseudoglioma
Childhood–adulthood
- Progressive sensorineural hearing loss (~30%)
- Intellectual disability (subset)
- Psychotic features (subset)
Diagnosis
- Ocular ultrasound/MRI: Retinal dysplasia, vitreous mass
- Genetic testing: NDP sequencing — confirms diagnosis
- Audiological evaluation: Annual hearing assessment
- Neurodevelopmental assessment: Cognitive and behavioral evaluation
Current Research & Treatment
No approved treatments restore vision in Norrie disease. Management focuses on hearing rehabilitation (hearing aids, cochlear implants) and developmental support. Norrin replacement therapy and gene therapy are in early preclinical stages.
Active Clinical Trials
The following active clinical trials are investigating treatments for Norrie Disease. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.