This child has xeroderma pigmentosum (XP), a disease in which there is a mutation in endonucleases involved in repairing pyrimidine dimers formed by exposure to ultraviolet (UV) light. Patients with XP are very sensitive to UV light exposure and have an increased risk of cutaneous malignancies, including malignant melanoma.
XP is an autosomal recessive disease in which there is a defect in the DNA repair mechanisms. In particular, in XP repair in response to DNA damaged by ultraviolet (UV) light is deficient. This disease affects approximately 1 in 250,000 people in the United States. XP often leads to extreme sunlight sensitivity with severe sunburns, freckling, dry and scaly skin, photophobia, corneal ulcers, and ocular cancers. XP patients have an increased risk for cutaneous malignancies; metastatic melanoma and squamous cell carcinoma are the leading cause of death in patients with XP.
Tamura et al. review the implementation of photoprotection in patients with XP. They state that patients with XP have a 10,000-fold increased risk of cutaneous malignancies and that approximately one quarter of patients experience neurodegenerative symptoms, including ataxia, hearing loss, and dysphagia. Although there is not a curative therapy for XP, UV protection is the primary treatment and helps to prevent many of the symptoms and complications associated with XP. Patients are recommended to avoid sunlight if possible and to consistently utilize protective measures such as sunglasses, face shields, and sunscreen.
Menck et al. discuss how DNA repair diseases such as XP relate to the process of aging. They describe that XP patients experience a multitude of skin-aging lesions by the age of 10 years old, ranging from pre-cancerous actinic keratosis to melanomas and other skin cancers. They also describe the incidence of XP across the world. While in the United States it affects 1 in 250,000 people, the incidence is much higher in Japan and North Africa, where the incidence may exceed 1 in 20,000 people.
Illustration A shows a child with XP with severe sunburns, freckling, and skin lesions.
Answers 1,2: Hereditary nonpolyposis colorectal cancer (HNPCC), rather than XP, is commonly associated with an increased risk of colorectal and endometrial cancer. It is commonly associated with an increased risk of both colorectal and endometrial cancer. HNPCC is due to a defect in mismatch repair genes.
Answer 3,4: Ataxia telangiectasia, rather than XP, is commonly associated with an increased risk for telangiectasias and lymphomas. Ataxia telangiectasia is due to an error in nonhomologous end joining during double strand DNA repair.
Tamura D, DiGiovanna JJ, Khan SG, Kraemer KH. Living with xeroderma pigmentosum: comprehensive photoprotection for highly photosensitive patients. Photodermatol Photoimmunol Photomed. 2014 Apr-Jun;30(2-3):146-52. doi: 10.1111/phpp.12108. Epub 2014 Feb 19. Review. PubMed PMID: 24417420.
PMID:24417420 (Link to Abstract)
Menck CF, Munford V. DNA repair diseases: What do they tell us about cancer and aging? Genet Mol Biol. 2014 Mar;37(1 Suppl):220-33. Review. PubMed PMID: 24764756; PubMed Central PMCID: PMC3983582.
PMID:24764756 (Link to Abstract)