X-linked congenital stationary night blindness is a disorder of the retina, which is the 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 loss of sharpness (reduced 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 by this disorder.

The vision problems associated with this condition are congenital, which means they are present from birth. They 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 cause and by the results of a test called an electroretinogram, which measures the function of the retina.

Mutations in the NYX and CACNA1F genes cause the complete and incomplete forms of X-linked congenital stationary night blindness, respectively. The proteins produced from these genes play critical roles in the retina.

Within the retina, the NYX and CACNA1F proteins are located on the surface of light-detecting cells called photoreceptors. 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 other retinal cells called bipolar cells, which is an essential step in the transmission of visual information from the eyes to the brain.

Mutations in the NYX or CACNA1F gene disrupt the transmission of visual signals between photoreceptors and retinal bipolar cells, which impairs vision. In people with the complete form of X-linked congenital stationary night blindness (resulting from NYX mutations), the function of rods is severely disrupted, while the function of cones is only mildly affected. In people with the incomplete form of the condition (resulting from CACNA1F mutations), rods and cones are both affected, although they retain some ability to detect light.

Normal Function

The NYX gene provides instructions for making a protein called nyctalopin, which plays an important role in a specialized tissue at the back of the eye called the retina. Within the retina, nyctalopin is located on the surface of light-detecting cells called photoreceptors. The retina contains two types of photoreceptors: rods and cones. Rods are responsible for vision in low light. Cones provide vision in bright light, including color vision.

Nyctalopin appears to play a critical role in normal vision. Studies suggest the protein helps relay visual signals from rods and cones to other retinal cells called bipolar cells. This signaling is an essential step in the transmission of visual information from the eyes to the brain.

Health Conditions Related to Genetic Changes

X-linked congenital stationary night blindness

More than 50 mutations in the NYX gene have been identified in people with X-linked congenital stationary night blindness. Mutations in this gene are responsible for the complete form of the disorder, which is characterized by difficulty seeing in low light (night blindness), loss of sharpness (reduced acuity), severe nearsightedness (high myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus).

Many NYX mutations change single protein building blocks (amino acids) in nyctalopin. NYX mutations can change the size or shape of the protein or prevent it from attaching to the surface of photoreceptor cells. A loss of functional nyctalopin disrupts the ability of photoreceptor cells to transmit visual signals, which impairs vision. The function of rods is severely disrupted, while the function of cones is only mildly affected.

Other disorders

At least two mutations in the NYX gene have been found to cause high myopia without the other vision problems characteristic of X-linked congenital stationary night blindness. The mutations responsible for high myopia each change a single amino acid in nyctalopin, which is predicted to result in an unstable protein. Researchers are uncertain why these mutations cause high myopia without any other vision abnormalities.

Other Names for This Gene

• CLRP
• CSNB1
• CSNB1A
• CSNB4
• leucine-rich repeat protein
• MGC138447
• NYX_HUMAN

Genomic Location

Normal Function

The CACNA1F gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium atoms (calcium ions) across cell membranes, play a key role in a cell's ability to generate and transmit electrical signals.

The CACNA1F gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV1.4. This subunit forms the hole (pore) in the cell membrane through which calcium ions can flow. CaV1.4 channels are found in many types of cells, although they play a particularly important role in a specialized tissue at the back of the eye called the retina. Within the retina, the channels are located in light-detecting cells called photoreceptors. The retina contains two types of photoreceptors: rods and cones. Rods are responsible for vision in low light. Cones provide vision in bright light, including color vision.

CaV1.4 channels appear to play a critical role in normal vision. Studies suggest they help relay visual signals from rods and cones to other retinal cells called bipolar cells. This signaling is an essential step in the transmission of visual information from the eyes to the brain.

Health Conditions Related to Genetic Changes

X-linked congenital stationary night blindness

More than 70 mutations in the CACNA1F gene have been identified in people with X-linked congenital stationary night blindness. Mutations in this gene are responsible for the incomplete form of the disorder, which is characterized by vision problems including a loss of sharpness (reduced acuity), nearsightedness (myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus). Many affected individuals also have difficulty seeing in low light (night blindness).

CACNA1F mutations change the structure of the alpha-1 subunit, which alters or eliminates the function of CaV1.4 channels. These changes prevent the normal transport of calcium ions across the cell membrane of photoreceptor cells. A loss of calcium ion transport disrupts the ability of both rods and cones to transmit visual signals, which impairs vision.

Cone-rod dystrophy

MedlinePlus Genetics provides information about Cone-rod dystrophy

Other disorders

Mutations in the CACNA1F gene cause several other rare disorders that impair vision. These include Åland Island eye disease, X-linked cone-rod dystrophy, an X-linked retinal disorder in New Zealand, and retinal and optic disc atrophy. Each of these disorders has been reported in only a few individuals or families worldwide. They cause vision problems similar to those of X-linked congenital stationary night blindness.

Researchers have identified at least one CACNA1F mutation that can cause Åland Island eye disease (also known as Forsius-Eriksson syndrome). This condition was first described in a family from the Åland Islands, which are in the Baltic Sea off the coast of Sweden. Åland Island eye disease is characterized by reduced visual acuity, nystagmus, an irregular curvature of the front part of the eye (astigmatism), myopia, abnormal color vision, and night blindness. The mutation associated with this disorder deletes a segment of genetic material from the CACNA1F gene, which significantly alters the structure of the alpha-1 subunit of CaV1.4 channels. These changes prevent the normal transport of calcium ions across the cell membrane of photoreceptor cells. A loss of calcium ion transport disrupts the ability of both rods and cones to transmit visual signals.

At least one other CACNA1F mutation is responsible for X-linked cone-rod dystrophy (also known as CORDX3). The signs and symptoms of this condition include reduced visual acuity, an increased sensitivity to light (photophobia), myopia, and impaired color vision. These vision problems tend to worsen over time. The mutation associated with this disorder deletes part of the alpha-1 subunit, which likely prevents the production of functional CaV1.4 channels. A loss of these channels keeps photoreceptor cells from relaying visual signals normally, which leads to impaired vision.

A CACNA1F mutation has also been found to cause an X-linked retinal disorder in a large Maori family from New Zealand. The major features of this disorder include reduced visual acuity, abnormal color vision, photophobia, and mild nystagmus. Some affected individuals have also had intellectual disability. The CACNA1F mutation associated with this condition alters a single protein building block (amino acid) in the alpha-1 subunit, which appears to overactivate CaV1.4 channels. The resulting increase in calcium ion transport probably disrupts the transmission of visual signals in the retina.

Another eye disorder, known as retinal and optic disc atrophy, has been associated with a CACNA1F mutation in two Japanese brothers. The affected individuals experienced a progressive decline in visual acuity and color vision. These vision problems were caused by deterioration of the retina, including an area called the optic disc (which is where the retina connects with the nerve that relays visual information to the brain). The CACNA1F mutation responsible for retinal and optic disc atrophy alters the structure of the alpha-1 subunit, which probably leads to the production of nonfunctional CaV1.4 channels. This mutation has also been identified in at least one Japanese family with X-linked congenital stationary night blindness. It is unclear why this single genetic change can cause different vision abnormalities in different families.

Other Names for This Gene

• AIED
• CAC1F_HUMAN
• calcium channel, voltage-dependent, L type, alpha 1F subunit
• Cav1.4
• Cav1.4alpha1
• COD3
• COD4
• CORDX
• CORDX3
• CSNB2
• CSNB2A
• CSNBX2
• JM8
• JMC8
• OA2

Genomic Location

This condition 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 males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. Carriers of an NYX or CACNA1F mutation can pass on the mutated 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.

Yes. About 45% of individuals with XLCSNB have the complete form, which is caused by mutations in the NYX gene. The other 55% have the incomplete form, which is caused by mutations in the CACNA1F gene.

Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

The prevalence of this condition is unknown. It appears to be more common in people of Dutch-German Mennonite descent. However, this disorder has been reported in families with many different ethnic backgrounds. The incomplete form is more common than the complete form.