OMIM ID:
Norrie Disease
Alternate Names
Defective Genes
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.
Genetics
Inheritance
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.
Pedigree
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.