Children living with Norrie Disease are born blind and are typically diagnosed within the first month of life. Diagnosis is based on clinical findings within the eye as well as genetic testing. Almost all patients will eventually experience profound deafness. Some patients will also experience multiple neurologic symptoms such as autism, cognitive impairment, seizures, etc.

Norrie Disease is a rare X-linked recessive genetic disorder. It is caused by a mutation in the NDP (Norrie Disease Protein) gene, which codes for a protein called norrin. Norrin protein is expressed throughout the body and has major roles in the eyes, ears, brain. When a mutation occurs in the gene, a functioning norrin protein cannot be produced by the body to effectively perform its job. For example norrin helps with proper pre-natal eye development, so without a working protein babies with Norrie disease are born with detached retinas, making them blind. The disease affects mostly males and is one of the most severe genetically based eye diseases. 

Norrie Disease is extremely rare. There are approximately 500 known cases in the world and some have cited a prevalence of 1 in 1 million occurrence. Because it is so rare, there has been little research and investment put in to study this disease, despite the range of debilitating symptoms that affect patients throughout their lives. While the underlying mechanism that causes blindness is well documented, there is little understanding of why Norrie Disease causes hearing loss and neurological symptoms.  

Through supporting research, the Foundation to Treat Norrie Disease hopes to shed light on the non-eye symptoms of the disease and help families better manage and treat this debilitating condition.

The known symptoms of Norrie Disease are centered around:

·       Eye: Without the proper norrin protein, infants while in utero are not able to develop normal vasculature in the eye. Typically, the blood vessels in the eye will bring nourishment and oxygen to the developing retina. With Norrie Disease, the blood vessels do not form appropriately and the retina become detached from the back of the eye. During this process, scar tissues form and create a grayish-yellow mass behind the eye called leukocoria. This results in severe blindness in both eyes in Norrie Disease babies at birth or during very early infancy. By the time the baby turns 1, there is typically no light perception, which causes circadian rhythm and sleep issues such as Non-24. Over time, eyes may also develop glaucoma, cataracts, and become phthisical (eye globe shrinkage).

·       Ear: In addition to the development of normal blood vessels in the eye, the protein norrin also helps with the maintenance of small vasculature in the inner ear. Patients are typically born with normal hearing and inner ear structure. However, over time, the lack of maintenance through inner ear stria vascularis creates cochlear damage. The vast majority of patients with Norrie Disease develop progressive sensorineural hearing loss starting during adolescence, although the range of presentation of hearing loss can be between 5–48 years. The hearing loss begins as intermittent, high frequency, asymmetric, and progresses to severe, flat, and symmetric in both ears.

·       Brain: Scientists have found norrin to be expressed in multiple areas in the brain. The exact function at this point is unknown. However, cognitive impairment, autism, and psychotic features are often manifestations of the disease. Approximately 30-50 percent of individuals with Norrie disease may experience cognitive abnormalities including delays in reaching developmental milestones. Patients could also show behavioral problems including psychosis, aggressive behavior and cognitive regression. Intellectual disabilities have been reported in 20-30% of patients. Autism and autistic like features, such as labile effect, perseveration, attention deficit disorder, etc.

·       Peripheral Vascular Disease: It is also common for Norrie disease patients to experience peripheral vascular disease, defined as varicose veins, peripheral venous stasis ulcers, and erectile dysfunction. The cause of this is unknown but somewhat consistent with the understanding that norrin is a vasculature protein that serves to maintain the small blood vessels throughout the body. Malfunctioning norrin therefore hinders blood vessel development and maintenance throughout the body.