ERCC2-related disorders are conditions where people become very sensitive to sunlight, causing severe sunburns even with little sun exposure.
The ERCC2 gene is important because it helps control other genes and repairs DNA damage that happens throughout a person’s life. There are different types of ERCC2-related disorders, including Xeroderma Pigmentosum (XP), the XP/Cockayne syndrome complex (XP/CS complex), Trichothiodystrophy (TTD), and Cerebro-oculofacial-skeletal syndrome (COFS). It’s hard to know exactly which form someone will develop based on their specific genetic changes, and some people might show signs of more than one type of ERCC2-related disorder.
Xeroderma Pigmentosum (XP) – this sensitivity can cause severe damage to the skin, especially around the eyes, tongue, and lips, and increases the risk of skin and eye cancers thousands of times. It also affects the nervous system, leading to problems with hearing and movement. Symptoms usually appear before age 10 and can be treated with medicines or surgery, but the risk of cancer from sun exposure is very high and can be life-threatening.
XP/Cockayne syndrome complex (XP/CS complex) – with this form of the disorder, people have symptoms of XP and these individuals can also have distinct facial features, growth issues, intellectual disability, hearing loss, and brain abnormalities.
Trichothiodystrophy (TTD) – this condition affects many parts of the body. Common symptoms include short, brittle hair that lacks sulfur, premature birth with low weight, and skin shedding like parchment. Other signs are delays in development or learning, short stature, dry skin, eye problems, infections that come back, and bone issues. Treatments are management focused, with the care of infections, eye problems, and bone issues as the higher priority.
Cerebro-oculofacial-skeletal syndrome (COFS) – this is a degenerative disease which is characterized by brain atrophy, calcification, cataracts, deterioration of the eyes, growth failure, and progressive joint contracture
This group of conditions is caused by pathogenic (disease-causing) variants in the ERCC2 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance of having a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Resources:
National Organization for Rare Disorders
Written August 2024
