What are ERCC6-related Disorders?
ERCC6-related disorders, caused by harmful genetic changes (mutations) in the gene ERCC6, are more commonly known as Cockayne syndrome type B. 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. Affected individuals may also have certain facial features such as a small chin, large ears, and a slender nose, which may make them appear older than their actual age.
There are three forms of ERCC6-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 ERCC6-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 most severe 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. 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 ERCC6-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 ERCC6 account for 65% of individuals affected with Cockayne syndrome. Studies suggest the condition may be more common in certain populations, such as the Druze population in northern Israel, individuals from Reunion Island, and in individuals of French or British ancestry.
How are ERCC6-related Disorders treated?
There is no cure for ERCC6-related disorders. Treatment is focused on managing the symptoms of the condition. This may include medication for muscle stiffness, tremors, or seizures; physical therapy or 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 ERCC6-related Disorder?
The prognosis for ERCC6-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 most severe form of the condition, death by age 7 is typical. The average life expectancy for those with Cockayne syndrome type III is not currently known.