Written by: Lucky Annem
Medically reviewed by: Dr. Lohi Pratti
Xeroderma Pigmentosum (XP) is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation and an increased risk of skin cancer. In the United States, there are around 1 per million cases, while there are 45 per million cases in Japan. This essay aims to delve into the scientific understanding of XP, including its causes, genetic basis, clinical manifestations, and the challenges faced by individuals affected by this condition.
XP is primarily caused by mutations in genes involved in the nucleotide excision repair (NER) pathway. This pathway is responsible for repairing DNA damage induced by UV radiation. Mutations in specific genes, such as XP-A, XP-B, XP-C, XP-D, XP-E, XP-F, and XP-G, disrupt the NER process, leading to an accumulation of DNA damage and increased susceptibility to skin cancers. XP is inherited autosomally recessive and affects both men and women equally.
Individuals with XP exhibit a range of clinical manifestations due to their impaired DNA repair capabilities. Sun exposure results in severe sunburns, blistering, freckling, and dry, rough skin. Over time, repeated sun damage can lead to the development of multiple skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma. Ocular complications, such as photophobia and increased risk of eye tumors, are also common in XP patients. Typically, freckles and other pigmentary abnormalities are frequently found in patients before the age of two. About nine years old is the typical age at which someone with X{ gets their first non-melanoma skin cancer, and about 22 years old is the median age at which they get their first malignant melanoma.
The underlying mechanisms behind XP's heightened sensitivity to UV radiation lie in the compromised DNA repair processes. The NER pathway, which is disrupted in XP, plays a crucial role in identifying and repairing UV-induced DNA lesions. Failure to repair these lesions can result in the accumulation of DNA mutations, leading to the development of skin cancers and other related complications.
Management of XP involves strict sun protection measures, including wearing protective clothing, hats, and sunglasses, and limiting sun exposure. Regular dermatological surveillance and early detection of skin cancers are paramount. Additionally, genetic counseling and family support play a crucial role in managing XP, as it is an inherited condition. Despite these measures, individuals with XP face significant challenges in their daily lives, such as limited outdoor activities and social isolation due to their unique sun sensitivity.
Scientific research on XP aims to further unravel the genetic and molecular mechanisms underlying the disorder. Advances in gene therapy, DNA repair mechanisms, and targeted interventions hold promise for potential therapeutic strategies to improve the quality of life for XP patients. Furthermore, public awareness campaigns and educational initiatives are essential to promote understanding, support, and prevention strategies for individuals with XP.
It is recommended by physicians that patients with XP should frequently take vitamin D supplements because sun exposure is strictly prohibited. Patients can also get vitamin D via fortified meals, fish, eggs, mushrooms, and other foods high in vitamin D. Patients will require routine and early treatment of precancerous lesions and skin malignancies, as well as routine complete body skin examinations by a dermatologist. For the prevention of skin cancer, oral isotretinoin, oral niacinamide, topical imiquimod, and topical fluorouracil can be utilized.
Xeroderma Pigmentosum is a complex genetic disorder characterized by extreme sun sensitivity and a heightened risk of skin cancers. The identification of underlying genetic mutations and understanding of impaired DNA repair processes have shed light on the mechanisms driving XP's clinical manifestations. Continued research efforts, improved management strategies, and increased public awareness can contribute to better outcomes and enhanced quality of life for individuals living with XP.
Image Source: The Telegraph
References:
Cleaver, James E. “Diagnosis of Xeroderma Pigmentosum and Related DNA Repair-Deficient Cutaneous Diseases.” Current Medical Literature. Dermatology, vol. 13, no. 2, 2008, pp. 41–48, www.ncbi.nlm.nih.gov/pmc/articles/PMC3198809/.
Hiva Fassihi, et al. Deep Phenotyping of 89 Xeroderma Pigmentosum Patients Reveals Unexpected Heterogeneity Dependent on the Precise Molecular Defect. no. 9, Feb. 2016, https://doi.org/10.1073/pnas.1519444113.
Leung AK, Barankin B, Lam JM, Leong KF, Hon KL. Xeroderma pigmentosum: an updated review. Drugs Context [Internet]. 2022 Apr 25 [cited 2023 Jul 17];11:2022-2–5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045481/
Lucero R, Horowitz D. Xeroderma Pigmentosum. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Jul 17]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK551563/
“Ocular Manifestations of Xeroderma Pigmentosum - EyeWiki.” Aao.org, 29 Apr. 2023, eyewiki.aao.org/Ocular_Manifestations_of_Xeroderma_Pigmentosum.
“SSA - POMS: DI 23022.920 - Xeroderma Pigmentosum - 09/09/2020.” Ssa.gov, 9 Sept. 2020, secure.ssa.gov/poms.nsf/lnx/0423022920.
“Xeroderma Pigmentosum.” Cancer.net, 26 June 2012,
www.cancer.net/cancer-types/xeroderma-pigmentosum.
“Xeroderma Pigmentosum: MedlinePlus Genetics.” Medlineplus.gov, 2022, medlineplus.gov/genetics/condition/xeroderma-pigmentosum/.
“Xeroderma Pigmentosum.” Mount Sinai Health System, 2020,
www.mountsinai.org/health-library/diseases-conditions/xeroderma-pigmentosum.
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