Norrie disease is an X-linked recessive genetic disorder that primarily affects the retina and causes a number of ocular complaints in the first several months of life. Leukocoria, atrophy of the iris, cataracts, and irreversible blindness are common features. Several extraocular features have been identified, including sensorineural hearing loss, mental retardation, and seizures. The diagnosis is made by observing typical clinical findings, a thorough examination, and genetic testing to confirm specific mutations.
Norrie disease is a rare X-linked recessive disorder that stems from mutations in the Norrie disease gene (NDP) that is located on chromosome X   . Although the exact pathogenesis remains unknown, mutations of NDP lead to an improper synthesis of the protein norrin, responsible for the formation of blood vessels and neural networks, and one of the most important sites of NDP expression is the retina  . For this reason, the clinical presentation of Norrie disease is focused on ocular manifestations . One of the hallmarks of this X-linked recessive disorder is a very early (congenital) onset of blindness, usually in a bilateral and symmetrical fashion     . By 3 months of age, the majority of boys have no light perception, while other notable signs are leukocoria (fibrosis of the retina that causes whitish discoloration in the presence of light), retinal dysplasia or detachment (developing within the first few months of life), atrophy of the iris, cataracts, and a retrolental fibrovascular mass that is yellow-to-gray in color (termed pseudoglioma)  . In addition to ocular manifestations, which follow a progressive course, a substantial proportion of patients suffering from Norrie disease present with extraocular symptoms, most important being sensorineural hearing loss (encountered in approximately a third of cases) and mental retardation (seen in two-thirds)     . Although rare, seizures have been described in a subset of patients .
Clinical suspicion must be present in order to make the diagnosis of Norrie disease, but because of its rare occurrence in clinical practice (approximately 300 cases are documented in the literature up to 2005) , its recognition might not be easy. For this reason, the physician must obtain a complete patient history and perform a thorough physical examination in the presence of bilateral progressive blindness in boys without an apparent cause. Given the X-linked recessive nature of the disease, a complete family history (particularly from the mother) must be obtained , whereas the course of symptoms, as well as its progression, must be assessed (either with the patient or parents in the case of neonates, infants, or small children) as well. A close inspection of the eye can be crucial for identifying leukocoria, hemorrhagic insults from retinal detachments, cataracts, or pseudogliomas, after which a meticulous ophthalmological examination need to be conducted. Extraocular findings such as mental retardation and sensorineural hearing loss should also be evaluated using appropriate neurological testing. To confirm the diagnosis of Norrie disease, however, genetic testing that will be able to identify specific mutations in the NDP gene (a pathogenic variant) is necessary .