ERCC8-related disorders

What are ERCC8-related Disorders?

ERCC8-related disorders, caused by harmful genetic changes (mutations) in the gene ERCC8, are more commonly known as Cockayne syndrome type A. Cockayne syndromes are inherited disorders characterized by severe growth delay, a small head size, developmental delays, and intellectual disabilities. Other common features of the condition include an increased sensitivity to sunlight (photosensitivity), significant tooth decay, vision problems, and hearing loss. In addition, affected individuals may have certain facial features such a small chin, large ears, and a slender nose, which may make them appear older than their actual age.

There are three forms of ERCC8-related disorders, called Cockayne syndrome type I, Cockayne syndrome type II, and Cockayne syndrome type III. These forms differ in the age at which symptoms first appear and how fast the symptoms progress. However, the three forms are not completely distinct, with some patients having features consistent with more than one type.

Cockayne Syndrome Type I

This is the most common type of ERCC8-related disorder. Newborns with this type generally appear normal. However, their growth slows considerably within the first two years of life. With time, their length, weight, and head size are all significantly less than expected for their age. Affected children also develop vision and hearing problems that worsen over time, as well as neurological problems such as increased muscle tone, difficulty walking, tremors, seizures, feeding difficulties, and behavioral issues. Other possible symptoms include (but are not limited to) cataracts, frequent cavities, dry skin and hair, bone problems, and changes in the brain that can be seen on brain imaging.

Cockayne Syndrome Type II

This form is also called cerebro-oculo-facio-skeletal [COFS] syndrome or Pena-Shokeir syndrome type II. It is the severest form of the disease, with signs and symptoms appearing at birth or in the newborn period. Infants are small at birth and often have cataracts or other eye abnormalities (such as small corneas). With time, they continue to have significant problems with growth and severe developmental delays. Affected children are typically unable to speak and cannot sit or walk independently.

Cockayne syndrome type III

This is the mildest form of the condition, with symptoms appearing later in childhood. While affected children with this type have some of the features associated with Cockayne syndrome types I and II, their growth deficiency and developmental delays are not as severe.

How common are ERCC8-related Disorders?

The incidence of Cockayne syndrome is estimated to be 1 in 300,00 births, however the condition may be under diagnosed. Mutations in ERCC8 account for 35% of individuals affected with Cockayne syndrome. Studies suggest that the condition may be more common in certain populations in Northern Israel.

How are ERCC8-related Disorders treated?

There is no cure for ERCC8-related disorders. Treatment is focused on managing the symptoms of the condition. This may include medication for muscle stiffness, tremors, or seizures; physical therapy and assistive devices for mobility issues; educational programs for intellectual disabilities; feeding tubes for those with significant feeding difficulties; hearing aids for those with hearing loss; and standard therapies for the treatment of cataracts or other vision problems. In addition, aggressive dental care will help minimize the risk of cavities, and sun protection is necessary for managing photosensitivity, although exposure to excessive sunlight should be avoided. Metronidazole (a type of antibiotic) should also be avoided, as use of this medication can cause liver failure in individuals with Cockayne syndrome.

What is the prognosis for an individual with an ERCC8-related Disorder?

The prognosis for ERCC8-related disorders varies depending on the type of Cockayne syndrome. Most individuals with Cockayne syndrome type I die by the age of 20, with an average age at death of 12 years. However, survival past the age of 20 has been reported. For those with Cockayne syndrome type II, the severest form of the condition, death by the age of seven is typical. The average life expectancy for those with Cockayne syndrome type III is not currently known.