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.
The most prominent symptoms of Norrie Disease are ocular. The first visible finding is Leukocoria, a grayish-yellow pupillary reflex that originates from a mass of unorganized tissue behind the lens. This material, which possibly includes an already detached retina, may be confused with a tumor and thus is termed pseudoglioma.  However, an affected baby may have a normally sized eye globe and inconspicuous iris, anterior chamber, cornea and intraocular pressure. Over the first few months of life, complete or partial retinal detachment evolves. From the time they’re a baby through childhood, the patient may undergo progressive changes in the disease. These progressions include the formation of cataracts, deterioration of the iris with adhesions forming between the iris and the lens or the cornea, and shallowing of the anterior chamber which increases intraocular pressure that can become painful. As the situation worsens, there is corneal opacification, where the cornea becomes opaque, and band keratopathy. Intraocular pressure is lost and the globe shrinks. In the last stage of Norrie disease, the globes appear small and sunken in (phthisis bulbi) and the cornea appears to be milky . Norrie disease can also have cognitive and behavioral symptoms. Developmental delay and mental retardation are present in about 30-50% of males who have Norrie disease. Psychotic-like features and poorly characterized behavior abnormalities may also be present. Auditory symptoms are often common with Norrie disease. Progressive hearing loss starts in early childhood for a majority of males with the disease. Early hearing loss is sensorineural, mild and asymmetric. By adolescence, high-frequency hearing loss begins to appear. Hearing loss is severe, symmetric, and broad-spectrum by the age of 35. However, studies show that while the hearing loss is deteriorating, the ability to speak well is highly preserved. The slowly progressing hearing loss is more problematic in adjusting to than the congenital blindness for most people with Norrie disease
Norrie Disease is a genetic disorder caused by mutations in the NDP gene, located on Xp11.4 (GeneID: 4693). It is inherited in an X-linked recessive way from usually one of your parents. This means that almost only males are affected. Sons of affected men will not have the mutation, while all of their daughters will be genetic carriers of the mutation. They also usually show no clinical symptoms, but will inherit the mutation to 50% of their offspring. Daughters receiving the mutated gene will also be, like their mother, asymptomatic carriers, but 50% of their sons will express clinical symptoms. Females are very unlikely to express clinical signs. One possible scenario leading to this (unlikely) case would be if both of their copies of the NDP gene bear mutations, which could be the case in consanguineous families or due to a spontaneous somatic mutation. Another explanation for affected females could be skewed X-Chromosome inactivation. However, throughout history, there have been a few rare cases where females have shown symptoms associated with Norrie Disease such as retinal abnormalities and mild hearing loss
As of right now, Norrie Disease and other NDP related diseases are diagnosed with the combination of clinical findings and molecular genetic testing. Molecular genetic testing identifies the mutations that cause the disease in about 85% of affected males. Clinical diagnoses rely on ocular findings. Norrie Disease is diagnosed when grayish-yellow fibrovascular masses are found behind the eye from birth through three months. Doctors also look for progression of the disease from three months through eight-ten years of age. Some of these progressions include cataracts, iris atrophy, shallowing of anterior chamber, and shrinking of the globe. By this point, the vision is light perception impaired or non-existent. Molecular genetic testing is used for more than an initial diagnosis. It is used to confirm diagnostic testing, for carrier testing females, prenatal diagnosis, and preimplantion genetic diagnosis. There are three types of clinical molecular genetic testing. In approximately 85% of males, mis-sense and splice mutations of the NDP gene and partial or whole gene deletions are detected using sequence analysis. Deletion/duplication analysis can be used to detect the 15% of mutations that are submicroscopic deletions. This is also used when testing for carrier females. The last testing used is linkage analysis, which is used when the first two are unavailable. Linkage analysis is also recommended for those families who have more than one member affected by the disease