Norrie Disease

Clinical Characteristics
Ocular Features: 

Norrie disease often presents at birth or soon thereafter with leukocoria.  There may be no response to light even at this early stage.  Microphthalmos, iris atrophy, and synechiae are often noted as well.  The posterior chamber contains a whitish-yellow mass associated with retinal folds and sometimes retinal detachment (pseudoglioma).  The vitreous may appear membranous and fibrovascular, often with traction on the retina.  Cataracts frequently develop early.  These signs may be unilateral or bilateral.  Corneal abnormalities such as opacities or sclerocornea may be present.  The mass in the posterior pole has to be distinguished from a retinoblastoma but the appearance may also resemble familial exudative vitreoretinopathy, Coats disease, persistent hyperplastic vitreous retinopathy, or retinopathy of prematurity.

Histology shows hemorrhagic necrosis of an undifferentiated glial mass.  The primary defect seems to lie in the neuroretina with absence of the ganglion cells and dysplasia of the remaining layers.  Many eyes become phthisical.

Systemic Features: 

Many individuals have growth and developmental delays with cognitive impairment and/or behavioral disorders (50%).  Frank psychoses have been reported in some patients.  Approximately 10% of patients have a chronic seizure disorder. Sensorineural deafness of some degree develops by the second decade in up to 100% of individuals.

Peripheral vascular disease (varicose veins, venous stasis ulcers, and erectile dysfunction) is present in nearly all men over the age of 50 years, perhaps the result of small vessel angiopathy.  Its age of onset is similar to that of the hearing deficit and the time course of progression is similar.


This is an X-linked disorder as a result of mutations in the NDP gene (Xp11.4) encoding norrin.  Many mutations causing Norrie disease are novel or at least rare as might be expected for a disorder that leads to a marked reduction in reproductive fitness in males.  Carrier females usually do not have any evidence of disease.

Mutations in NDP also are responsible for a sex-linked form of familial exudative vitreoretinopathy, EVR2 (305390).  They have also been found in some cases of persistent hyperplastic primary vitreous and even in Coates' disease.  The latter conditions are usually present unilaterally, however, and some consider bilaterality to be a characteristic of NDP-related retinopathies.

Treatment Options: 

No effective treatment is available.

Article Title: 

Mutations in the Norrie disease gene

Schuback DE, Chen ZY, Craig IW, Breakefield XO, Sims KB. Mutations in the Norrie disease gene. Hum Mutat. 1995;5(4):285-92.

PubMed ID: 


Smith SE, Mullen TE, Graham D, Sims KB, Rehm HL. Norrie disease: Extraocular clinical manifestations in 56 patients. Am J Med Genet A. 2012 Jul 11. doi: 10.1002/ajmg.a.35469. [Epub ahead of print] PubMed PMID: 22786811.

PubMedID: 22786811

Kondo, H., Qin, M., Kusaka, S., Tahira, T., Hasebe, H., Hayashi, H., Uchio, E., Hayashi, K. Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy. Invest. Ophthal. Vis. Sci. 48: 1276-1282, 2007.

PubMedID: 17325173

Chen, Z.-Y., Battinelli, E. M., Fielder, A., Bundey, S., Sims, K., Breakefield, X. O., Craig, I. W. A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy. Nature Genet. 5: 180-183, 1993.

PubMedID: 8252044

Schuback DE, Chen ZY, Craig IW, Breakefield XO, Sims KB. Mutations in the Norrie disease gene. Hum Mutat. 1995;5(4):285-92.

PubMedID: 7627181