NORRIE DISEASE
Named after the Danish ophthalmologist Gordon Norrie, Norrie disease (ND) is a rare genetic disorder caused by mutations of a single gene.
The gene plays an important role in the development and maintenance of blood vessels, most notably in the eyes, ears, and brain.
Affected patients are born blind or lose their vision in infancy.
They suffer from progressive hearing loss which leads to profound deafness in mid to late adulthood.
Up to 50% of affected individuals manifest neurological symptoms such as epileptic seizures, cognitive impairment, and autism.
Most – if not all – ND men over the age of 50 experience peripheral venous insufficiency, resulting in varicose veins, leg ulcers, and erectile dysfunction.
The Norrie disease gene is located on the X chromosome. The inheritance pattern is X-linked recessive. Only males manifest the symptoms whereas females are carriers. Where a female carries the mutation, there will be a 50% risk that a male offspring will inherit the disease, and a 50% risk that a female offspring will be a carrier. Where a male is affected, male offsprings are unaffected whereas 100% of female offsprings are carriers.
Below is a list of published research about ND, or of relevance to ND, shown in three categories:
- Stopping the progression of hearing loss in ND
- Brain abnormality in ND
- Blood brain barrier repair in neurological disorders
Stopping the progression of hearing loss in ND
As Norrie disease gene therapy for hearing loss approaches pre-clinical research, the list below comprises only the most recent research (2021 onwards):
- Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities (Ferenchak et al, 2025)
- Rescue of cochlear vascular pathology prevents sensory hair cell loss in Norrie disease (Patel et al, 2024)
- Abnormal cochlear enhancement in Norrie disease (Barkovich et al, 2024)
- Systemic gene therapy rescues retinal dysfunction and hearing loss in a model of Norrie disease (Pauzuolyte et al, 2023)
- Norrie disease protein is essential for cochlear hair cell maturation (Hayashi et al, 2021)
Brain abnormality in ND
- Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities (Ferenchak et al, 2025)
- Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin (Miller et al, 2019)
- Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain (Ye et al, 2011)
- Differentiation of the brain vasculature: the answer came blowing by the Wnt (Liebner et al, 2010)
- Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled-4 (Luhmann et al, 2008)
Blood brain barrier repair in neurological disorders
- Therapeutic blood-brain barrier modulation and stroke treatment by a bioengineered FZD4-selective WNT surrogate in mice (Ding et al, 2023)
- Engineered Wnt ligands enable blood-brain barrier repair in neurological disorders (Martin et al, 2022)