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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Norrie disease

Reviewed March 2007

What is Norrie disease?

Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. It causes abnormal development of the retina, the layer of sensory cells that detect light and color, with masses of immature retinal cells accumulating at the back of the eye. As a result, the pupils appear white when light is shone on them, a sign called leukocoria. The irises (colored portions of the eyes) or the entire eyeballs may shrink and deteriorate during the first months of life, and cataracts (cloudiness in the lens of the eye) may eventually develop.

About one third of individuals with Norrie disease develop progressive hearing loss, and more than half experience developmental delays in motor skills such as sitting up and walking. Other problems may include mild to moderate intellectual disability, often with psychosis, and abnormalities that can affect circulation, breathing, digestion, excretion, or reproduction.

How common is Norrie disease?

Norrie disease is a rare disorder; its exact incidence is unknown. It is not associated with any specific racial or ethnic group.

What genes are related to Norrie disease?

Mutations in the NDP gene cause Norrie disease.

The NDP gene provides instructions for making a protein called norrin. Norrin participates in the Wnt cascade, a sequence of steps that affect the way cells and tissues develop. In particular, norrin seems to play a critical role in the specialization of retinal cells for their unique sensory capabilities. It is also involved in the establishment of a blood supply to tissues of the retina and the inner ear, and the development of other body systems.

In order to initiate the Wnt cascade, norrin must bind (attach) to another protein called frizzled-4. Mutations in the norrin protein interfere with its ability to bind to frizzled-4, resulting in the signs and symptoms of Norrie disease.

Related Gene(s)

Changes in this gene are associated with Norrie disease.

  • NDP

How do people inherit Norrie disease?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. In rare cases, however, carrier females have shown some retinal abnormalities or mild hearing loss associated with Norrie disease.

Where can I find information about diagnosis or management of Norrie disease?

These resources address the diagnosis or management of Norrie disease and may include treatment providers.

  • Gene Review: NDP-Related Retinopathies (
  • Genetic Testing Registry: Atrophia bulborum hereditaria (

You might also find information on the diagnosis or management of Norrie disease in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about Norrie disease?

You may find the following resources about Norrie disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Norrie disease?

  • Anderson-Warburg syndrome
  • Atrophia bulborum hereditaria
  • congenital progressive oculo-acoustico-cerebral degeneration
  • Episkopi blindness
  • Fetal iritis syndrome
  • Norrie's disease
  • Norrie syndrome
  • Norrie-Warburg syndrome
  • Oligophrenia microphthalmus
  • pseudoglioma congenita
  • Whitnall-Norman syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about Norrie disease?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Norrie disease?

carrier ; cell ; chromosome ; congenital ; digestion ; disability ; dysplasia ; excretion ; gene ; incidence ; inheritance ; inherited ; motor ; mutation ; protein ; pseudoglioma ; psychosis ; recessive ; reproduction ; retina ; sensory cells ; sex chromosomes ; sign ; syndrome ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Clevers H. Wnt signaling: Ig-norrin the dogma. Curr Biol. 2004 Jun 8;14(11):R436-7. Review. (
  • Lenzner S, Prietz S, Feil S, Nuber UA, Ropers HH, Berger W. Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells. Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2825-33. (
  • Michaelides M, Luthert PJ, Cooling R, Firth H, Moore AT. Norrie disease and peripheral venous insufficiency. Br J Ophthalmol. 2004 Nov;88(11):1475. Erratum in: Br J Ophthalmol. 2005 May;89(5):645. (
  • National Organization for Rare Disorders (NORD) (
  • Ott S, Patel RJ, Appukuttan B, Wang X, Stout JT. A novel mutation in the Norrie disease gene. J AAPOS. 2000 Apr;4(2):125-6. (
  • Rehm HL, Zhang DS, Brown MC, Burgess B, Halpin C, Berger W, Morton CC, Corey DP, Chen ZY. Vascular defects and sensorineural deafness in a mouse model of Norrie disease. J Neurosci. 2002 Jun 1;22(11):4286-92. (
  • Royer G, Hanein S, Raclin V, Gigarel N, Rozet JM, Munnich A, Steffann J, Dufier JL, Kaplan J, Bonnefont JP. NDP gene mutations in 14 French families with Norrie disease. Hum Mutat. 2003 Dec;22(6):499. (
  • Suárez-Merino B, Bye J, McDowall J, Ross M, Craig IW. Sequence analysis and transcript identification within 1.5 MB of DNA deleted together with the NDP and MAO genes in atypical Norrie disease patients presenting with a profound phenotype. Hum Mutat. 2001 Jun;17(6):523. (
  • Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004 Mar 19;116(6):883-95. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: March 2007
Published: February 8, 2016