CEP290-related disorders

What are CEP290-related disorders?

CEP290-related disorders are characterized by a wide spectrum of symptoms and severities that range from birth defects and stillbirth to isolated vision loss. They are caused by harmful genetic changes (variants) in the CEP290 gene. Individuals with CEP290-related disorders have abnormalities in a part of a cell called cilia, which is the cause of their symptoms. Cilia are hair-like structures that stick out from cells and are essential for cellular movement and sensory functions. Individuals with CEP290-related disorders have abnormalities of the cilia, which is the cause of their symptoms.

Variants in CEP290 cause several different disorders, including Meckel-Gruber syndrome, Joubert syndrome, and Leber congenital amaurosis. Symptoms overlap between the different forms, and it can be difficult to predict which form an individual will have based on their specific CEP290 variants alone.

Leber congenital amaurosis

Leber congenital amaurosis (LCA) is characterized by severe vision loss that begins in infancy. Individuals may show abnormal eye movements and sensitivity to light. Multiple genes can cause LCA, and LCA due to variants in CEP290 is known as LCA type 10. Unlike other CEP290-related disorders, LCA type 10 only affects the eyes.

Joubert syndrome

Individuals with Joubert syndrome have developmental delays, low muscle tone (hypotonia), and balance issues. A specific part of the brain, the cerebellum and brain stem, have a unique shape. When seen on a brain MRI, the shape appears somewhat like a tooth and is therefore called a “molar tooth sign.” Many newborns with Joubert syndrome have breathing issues. Other symptoms can include kidney disease, liver abnormalities, feeding problems, extra fingers and toes, vision loss, and abnormal eye movements. Most people with Joubert syndrome have intellectual disability. Many genes can cause Joubert syndrome. Joubert syndrome caused by variants in CEP290 is known as Joubert syndrome type 5.

Meckel-Gruber syndrome

Meckel-Gruber syndrome, sometimes called Meckel syndrome, (MKS) is the most severe type of CEP290-related disorder. Individuals have birth defects including brain, liver, and kidney abnormalities. They often have extra fingers and toes. Other symptoms can include heart defects, cleft lip and palate, underdeveloped lungs, and bone abnormalities. Several genes can cause MKS. MKS caused by variants in CEP290 is known as MKS type 4.

How common are CEP290-related disorders?

Several genes are known to cause LCA, which has an incidence of 1 in 100,000 – 1 in 300,000 births. Approximately 20% of LCA is caused by CEP290. Several genes are also known to cause Joubert syndrome, which has an incidence of 1 in 80,000 – 1 in 100,000 births. Approximately 10% of Joubert syndrome is caused by CEP290. Finally, several genes are known to cause MKS, which has an incidence of 1 in 13,250 to 1 in 140,000 births. It is unknown what proportion of MKS is caused by CEP290.

How are CEP290-related disorders treated?

There is no cure for CEP290-related disorders. Treatment is directed at managing the specific symptoms an individual has. Individuals with vision loss caused by either LCA or Joubert syndrome may benefit from using glasses, low-vision aids, and supportive services for those with vision impairment.

Individuals with Joubert syndrome may receive care through a team of specialists, including physicians, speech pathologists, occupational therapists, physical therapists, and social workers. Some infants need supplemental oxygen or a breathing tube to help with breathing issues. Medications may be given to help manage symptoms such as breathing, liver, or kidney issues. In some cases, surgery is required to treat certain birth defects.

Because babies with MKS are typically stillborn or die shortly after birth, treatment for this condition is usually limited and aimed at improving comfort.

What is the prognosis for a person with a CEP290-related disorder?

The prognosis of CEP290-related disorders varies widely. Individuals with LCA typically have normal lifespans. Some individuals with Joubert syndrome will die in infancy or childhood, whereas others live into adulthood. Common causes of early death in Joubert syndrome include breathing-related issues and kidney disease. Babies with MKS are typically stillborn or die shortly after birth.