Xeroderma Pigmentosum (XP)
Description
Xeroderma pigmentosum (XP) is a rare genetic disorder that makes individuals extremely sensitive to ultraviolet (UV) radiation from sunlight. This sensitivity can lead to severe sunburns, premature skin aging, and an increased risk of developing skin cancer. XP is caused by mutations in genes involved in DNA repair, leaving cells vulnerable to UV damage. While there is no cure for XP, early diagnosis and careful management can help individuals with XP live longer, healthier lives.
Genes Involved
XP is caused by mutations in genes involved in DNA repair pathways. These genes help cells repair damage caused by UV radiation. Some of the genes associated with XP include:
- **ERCC3 (XPB)
- **ERCC2 (XPD)
- **XPA
- **XPC
- **XPE
- **XPF
- **XPG
- **DDB2
- **POLH
- **DCLRE1C (TREX1)
Mutations in these genes disrupt the DNA repair process, leaving cells susceptible to UV damage. This can lead to the development of various symptoms associated with XP.
Recognizing the Signs and Symptoms
The most noticeable sign of XP is extreme sensitivity to sunlight. Other symptoms may include:
- Sunburns: Even brief exposure to sunlight can cause severe sunburns.
- Freckles and Pigmentation Changes: Dark spots and patches may appear on sun-exposed skin.
- Dry, Scaly Skin: Skin can become dry, rough, and scaly, especially in areas exposed to the sun.
- Premature Aging: Skin may appear aged and wrinkled prematurely.
- Eye Problems: Cataracts, corneal damage, and other eye problems can develop.
- Skin Cancer: Individuals with XP have a significantly increased risk of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma.
Symptoms usually appear in childhood, often within the first few years of life. The severity of XP varies depending on the specific gene mutation and the amount of sunlight exposure.
Causes
XP is caused by inherited mutations in genes involved in DNA repair. These mutations are passed down from parents to their children. When a person inherits a mutated gene from both parents, they will develop XP. If they inherit a mutated gene from only one parent, they will be a carrier of the gene but may not develop XP themselves.
Inheritance/recurrence risk
XP is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. If both parents carry the mutated gene, there is a 25% chance for each child to inherit two copies of the mutated gene and develop XP, a 50% chance to inherit one copy of the mutated gene and be a carrier, and a 25% chance to inherit no copies of the mutated gene and not have XP. If one parent has XP and the other parent is a carrier, there is a 50% chance for each child to inherit the mutated gene and develop XP. If one parent has XP and the other parent does not carry the mutated gene, there is no chance for their children to develop XP.
