What Is Norrie Disease?
Norrie disease (ND) is a genetic disorder that affects the eyes primarily. Because it is inherited in an X-linked recessive manner, it affects males far more often than it does females. Specifically, ND affects the development of the retina of the eye to the extent that the cells of the retina that detect light and color are rendered partially or, as is more often the case, entirely dysfunctional. Due to the dysfunction to these retinal cells, blindness occurs. Blindness typically occurs in utero or shortly after birth. In limited cases, blindness does not occur until later in life.
In addition to blindness, individuals who have ND sometimes experience other defects, such as progressive hearing loss, occurring in about 30 percent of all ND affected people, the inability to carry out certain motor skills such as walking, for example, intellectual and mental abnormalities and certain problems that can affect breathing, circulation, digestion, and reproduction, to name a few.
Although the exact incidence of ND is unknown, it is very rare. Further, it is known that ND does not disproportionately affect any particular race or people of any particular national origin.
What Is Known About The Genetics Of Norrie Disease?
Human molecular geneticists have determined that ND is caused by mutations to a gene on the X chromosome that is designated NDP. The NDP gene encodes a protein that is referred to as norrin. It has been determined that norrin is involved in a process known as Wnt signaling. In proper Wnt signaling, cells are exposed to certain chemical stimuli, and in response to these stimuli, they carry out a series of steps (which collectively are referred to as the Wnt cascade) that are needed for normal development. To initiate one of the steps, norrin must bind to second protein, which is the product of a gene called "frizzled".
For unknown reasons, the binding of the norrin and frizzled proteins is particularly critical to cells that are found in the retina, and especially to those cells that are involved in the sensation of color and light. In ND affected individuals, mutations in the NDP gene cause either no norrin to be made or cause a defective version of the norrin protein to be made. In either case, the important Wnt cascade event in which norrin binds to the frizzled protein cannot occur. As a result of this molecular defect, the retinal cells of ND individuals do not develop properly and thus blindness results.
This article is only meant to provide some basic information regarding the genetic condition known as Norrie disease. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.
D.E. Schuback et al., Mutations in the Norrie disease gene, Human Mutation 5:285-292 (1995).
Genetics Home Reference, National Institutes of Health, NDP: https://ghr.nlm.nih.gov/gene/NDP
Genetics Home Reference, National Institutes of Health, Norrie disease: https://ghr.nlm.nih.gov/condition/norrie-disease