X-linked congenital stationary night blindness

X-linked congenital stationary night blindness is a disorder of the retina, which is a specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing in low light (night blindness). They also have other vision problems, including increased sensitivity to light (photophobia), loss of sharpness (reduced visual acuity), severe nearsightedness (high myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus). Color vision is typically not affected in people with X-linked congenital stationary night blindness.

The vision problems associated with X-linked congenital stationary night blindness are congenital, which means they are present from birth. The vision problems also tend to remain stable (stationary) over time.

Researchers have identified two major types of X-linked congenital stationary night blindness: the complete form and the incomplete form. The types have very similar signs and symptoms. However, everyone with the complete form has night blindness, while not all people with the incomplete form have night blindness. The types are distinguished by their genetic causes and by the results of a test called an electroretinogram, which measures the function of the retina.

The prevalence of X-linked congenital stationary night blindness is unknown. The incomplete form is more common than the complete form.

Variants (also called mutations) in the NYX gene cause the complete form of X-linked congenital stationary night blindness, and variants in the CACNA1F gene cause the incomplete form. The proteins produced from these genes play critical roles in the retina.

Within the retina, the CACNA1F protein is located on light-detecting cells called photoreceptors. The NYX protein is located on cells called bipolar cells, which relay signals to other retinal cells. The retina contains two types of photoreceptor cells: rods and cones. Rods are needed for vision in low light. Cones are needed for vision in bright light, including color vision. The NYX and CACNA1F proteins ensure that visual signals are passed from rods and cones to bipolar cells, which is an essential step in the transmission of visual information from the eyes to the brain.

Variants in the NYX or CACNA1F gene disrupt the transmission of visual signals between photoreceptors and bipolar cells, which impairs vision. In people with the complete form of X-linked congenital stationary night blindness, the rod pathway is severely disrupted, while the cone pathway is only mildly affected. In people with the incomplete form of the condition, the rod and cone pathways are both affected, although the affected person does have the ability to detect some light.

A particular variant in the CACNA1F gene has been found to cause X-linked congenital stationary night blindness in individuals who are of Dutch-German Mennonite descent. Similarly, certain NYX gene variants appear to be a frequent cause of X-linked congenital stationary night blindness in people who live in the United States and in people who live in Belgium and are of Flemish descent.

X-linked congenital stationary night blindness is inherited in an X-linked recessive pattern. The NYX and CACNA1F genes are located on the X chromosome, which is one of the two sex chromosomes. In individuals who have only one X chromosome (typical for males), one altered copy of the gene in each cell is sufficient to cause the condition. In people who have two X chromosomes (typical for females), a variant would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that both copies of a gene would be altered, people with one X chromosome are affected by X-linked recessive disorders much more frequently than those with two. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a person with one altered copy of the gene on one of their two X chromosomes is called a carrier. Carriers of an NYX or CACNA1F gene variant can pass on the altered gene, but most do not develop any of the vision problems associated with X-linked congenital stationary night blindness. However, carriers may have retinal changes that can be detected with an electroretinogram.