Norrie disease

Norrie disease
Specialty	Medical genetics

Norrie disease is a rare X-linked recessive genetic disorder that primarily affects the eyes and almost always leads to blindness. It is caused by mutations in the Norrin cystine knot growth factor gene, also referred to as Norrie Disease Pseudoglioma (NDP) gene.^[1][2] Norrie disease manifests with vision impairment either at birth, or within a few weeks of life, following an ocular event like retinal detachment and is progressive through childhood and adolescence. It generally begins with retinal degeneration, which occurs before birth and results in blindness at birth (congenital) or early infancy, usually by 3 months of age.^[3]

Patients with Norrie disease may develop cataracts, leukocoria (where the pupils appear white when light is shone on them), along with other developmental issues in the eye, such as shrinking of the globe and the wasting away of the iris.^[2]

In addition to the congenital ocular symptoms, the majority of individuals afflicted by this disease develop progressive hearing loss caused by vascular abnormalities in the cochlea. Hearing loss usually begins in early childhood and may be mild at first before becoming more progressive by the third or forth decade of life.^[4][5]

Roughly 30-50 percent of those affected by the disease might encounter cognitive challenges, learning difficulties, incoordination of movements or behavioral abnormalities.^[2] These developmental delays often surpass those expected from their visual impairment alone. Additionally, behavioral issues such as psychosis, aggression, and cognitive decline may manifest in patients. Intellectual disabilities have been observed in 20-30% of cases, while dementia, though uncommon, can emerge in late adulthood. About 15% of patients are estimated to develop all the features of the disease.^[6]

Due to the X-linked recessive pattern of inheritance, Norrie disease affects almost entirely males. Only in very rare cases, females have been diagnosed with Norrie disease; cases of symptomatic female carriers have been reported.^[7][8] It is a very rare disorder that is not associated with any specific ethnic or racial groups, with cases reported worldwide (including cases in North America, South America, Europe, Asia and Australasia).^{[9][10][11][12]} While more than 400 cases have been described, the prevalence and incidence of the disease still remains unknown.^[13][14]