Norrie Disease

Norrie disease (ND) is a rare X-linked disorder that occurs due to mutations of the NDP gene.

The clinical symptoms of ND comprise congenital blindness, late onset progressive hearing loss and, in up to 50% of cases, intellectual disabilities or behavioral difficulties which include autism-like features.

Other associated manifestations are highly variable and include chronic seizure disorder, peripheral vascular abnormalities such as venous insufficiency, and erectile dysfunction.

Affected patients are almost always male, while females are carriers.

The NDP gene encodes the protein norrin, which is involved in the vascular development and/or maintenance in the eye, the ear and the brain.

 

More about the 3 most common symptoms of ND:

Congenital blindness:

The main symptom of Norrie disease is a retinal degeneration which occurs in utero and results in blindness at birth (congenital) or early infancy. Visual failure in this disorder is characterized by the abnormal development of the retina (the thin layer of nerve cells that lines the back of the eyes).

In Norrie disease, the retinas separate from the underlying, supporting tissue (retinal detachment). This causes a grayish-yellow mass to develop in the back of eye behind the lens that may be mistaken for a tumor (pseudoglioma). This mass consists of immature retinal cells and may be apparent a few days after birth or may not be noted until weeks or months later. This mass is located behind the pupils of the eyes so that the pupils appear white, a condition known as leukocoria or “cat’s eye” reflex.

The eyes of affected children go through additional progressive changes. The lenses of the eyes of an affected infant may be initially clear. Eventually, clouding (opacity) of the front, clear portion of the eye through which light passes (cornea) may develop, a condition known as a cataract. In addition, as the disorder progresses, shrinking of the eyeballs (phthisis bulbi) may occur and is often apparent by ten years of age. Subsequently, the lenses are often completely covered by cataracts.

In addition, the eyes may be abnormally small (microphthalmia) at birth, the pupils may be widened (dilated) and the colored portion of the eyes (irises) may be underdeveloped (hypoplastic) and may stick to the lens (posterior synechiae) or may stick to the cornea (anterior synechiae). The space in the eye behind the cornea and in front of the iris (anterior chamber) may be abnormally shallow and the outflow tracts of the eye may be blocked (occluded), resulting in increased pressure with the eye (intraocular pressure) which may be extremely painful.

Hearing loss:

Most individuals with Norrie disease develop progressive hearing loss due to vascular abnormalities in the cochlea (inner ear). Hearing loss usually begins in late childhood or early adolescence and may be mild at first and slowly progressive. By the third or fourth decade there may be significant functional loss but it can usually be aide assisted. Speech discrimination is relatively well preserved. The development and severity of hearing loss varies greatly even among members of the same family. In some cases, hearing loss may not develop until adulthood.

Brain related problems:

Approximately 30-50 percent of individuals with Norrie disease may experience cognitive abnormalities including delays in reaching developmental milestones disproportional to vision loss. Some will show behavioral problems including psychosis, aggressive behavior and cognitive regression. Mental retardation has been reported in some cases.