Norrie Disease

At a glance

Rare inherited neurodevelopmental disorder characterized by congenital bilateral blindness and white pupils. Other features can include mental retardation, mild-to-profound hearing loss, and cataracts during early infancy. Phthisis bulbi (shrinking of the eye) has been reported.

Synonyms

Anderson-Warburg Syndrome; Fetal Iritis Syndrome; Whitnall-Norman Syndrome; Atrophia Bulborum Hereditaria; Congenital Progressive Oculo-Acoustico-Cerebral Degeneration; Norrie-Warburg Syndrome; Norrie Syndrome; Episkopi Blindness.

History

Initially described by Danish ophthalmologist Mette Warburg in 1961, who after extensive literature research, suggested that Danish ophthalmologist Gordon Norrie (1855-1941) should be credited.

Incidence

Very rare, more than 400 cases have been described. Clinical expression almost exclusively in males. Norrie disease has been described in patients of various ethnical backgrounds (White, Hispanic, Sri Lankan, Asian, and Canadian Indian).

Genetic inheritance

X-linked recessive disorder. Rare reports of presumed manifesting heterozygote females exist. More than 75 mutations have been identified.

Pathophysiology

The Norrie disease gene (NDP—Norrie Disease Pseudoglioma) is located on the short arm of chromosome X (Xp11.4). It consists of three exons and encodes for a protein named norrin with a cystine-knot motif, which activates the Wnt/beta-catenin pathway. This pathway regulates cell division, adhesion, migration, and many other cellular activities.

Diagnosis

Based on clinical features, mode of inheritance, and genetic testing.

Clinical aspects

Characterized by microphthalmia with bilateral degeneration of the retina and vitreous humor leading to early blindness, usually within the first week of life. Characteristic ocular findings include retinal detachment, vitreous hemorrhage, and formation of retrolental masses. Pupils are dilated with no light reflex. Cataracts. Phthisis bulbi (shrinkage of the eyeball) develops over the first decade of life. In approximately one-third of Norrie disease patients, progressive sensorineural hearing loss occurs, with age at onset varying from a few months of life to adulthood. Some degree of mental retardation is frequent (up to 50% of patients), although many individuals have normal intellectual capabilities. Several individuals with complex syndromic anomalies have been described in whom Norrie disease was part of the clinical findings. Associated anomalies in these cases included hypogonadism, increased susceptibility to infections, skeletal malformations, and a combination of facial features, including hypotelorism, narrow nasal bridge, thin upper lip, and large ears. Early vitrectomy has been used to mitigate the natural progression to blindness.

Precautions before anesthesia

No literature describing anesthetic experiences in Norrie disease patients. However, adequate anxiolysis is particularly important in patients with deafness and mental retardation.

Anesthetic considerations

Known features of Norrie disease do not suggest an increased risk of anesthesia.

Pharmacological implications

Submicroscopic deletions in ...