XP’s low incidence combined with it presenting itself as such a severe condition tends to make it a popular topic of interest among medical researchers. The literature review of this article includes the epidemiology of Xeroderma Pigmentosum, genetics of the disorder, and narratives of the occupants of this obscure yet globally significant disease’s gene pool.

The method used in the course of analyzing the epidemiology of Xeroderma Pigmentosum

As it has been pointed out, XP is, without doubt, an incredibly rare disease. They estimated that LEMS should occur in around 1000–1200 people across the United States and Europe and prevalence depends on the region for the rest of the world. The prevalence of Parkinson’s in Japan for instance is slightly higher with a range of 1:22000 to 1:100000. Such figures, however, are averages and, depending on geographic location, ethnic background, and genetic predisposition, can be considerably higher or lower.

XP is found more commonly in those populations with consanguinity, as the disorder is an autosomal recessive. This is to mean that both parents have to be carriers of the abnormal gene for their child to be born with the condition. Where the practice of consanguineous marriages is practiced, both parents are likely to be carriers of the same rare gene mutation that causes XP, thus increasing the occurrence of this genetic disorder. For instance, XP has been found to occur more frequently in North Africa and the Middle Eastern people than those from other parts of the world and this is partly due to the higher rate of consanguineous marriage among these people.

Genetic Underpinnings of Xeroderma Pigmentosum

Xeroderma Pigmentosum is genetically determined by mutation in any of the genes that are related to DNA repair. It is understood that when skin cell proliferate, they are exposed to ultraviolet light and this might lead to DNA damage. In healthy adults, specialized proteins which are products of DNA repair genes immediately identify this damage and repair in order to arrest the occurrence of mutations that may lead to cancer. However, in individuals with XP, these repair genes are mutated and consequently the body is unable to effectively fix the UV induced DNA damage hence posing a very high risk of skin cancers among other problems.

Sometimes genetic alteration occurs in a certain gene named POLH, which encodes proteins which make errors during replication past a damaged site, may result in a variant form of XP known as XP-V. XP-V patients may have slightly better prognosis compared to the other diseases linked to the NER pathway as their cells are still capable of analyzing the DNA damage to some extent, although incorrectly.

Clinical Manifestations and Challenges

As highlighted earlier, Xeroderma Pigmentosum Clinical expression in the body, specially perceived and visible body symptoms ,are quite dramatic. Their most striking characteristic is photographed photosensitivity and they can burn acutely even in a few minutes in direct sunlight. This photosensitivity is usually associated with the early development of freckles, especially of the face, neck and arms which are exposed to the sunlight. In the long run the parts of skin exposed to these areas may be developing actinic keratoses which are precancerous skin growth that may lead to formation of squamous cell carcinoma or other types of skin cancer.

Apart from skin cancers XP patients are also prone to develop ocular tumors like conjunctival melanoma and other tumors like tongue and brain. 

Living with Xeroderma Pigmentosum: The Human Experience

In healthy people specialized proteins, which are encoded by DNA repair genes, instantly detect this damage and bring correction to stop further build up of mutations that can lead to formation of cancer. Nevertheless, in the case of XP, the described repair genes are mutated and hence the body’s ability to repair the UV-induced DNA damage is significantly affected leading to skin cancers and other related complications.

Sometimes the defect of XP lies in the POLH gene affecting the process of replication past the lesions, known as XP variant (XP-V). Patients with XP-V might be expected to have a somewhat less severe disease phenotype due their cells’ residual capacity to bypass DNA damage even though this capacity is error-prone.

Clinical Manifestations and Challenges

The symptoms of XP are severe and diverse and include the following. The most outstanding characteristic is the photosensitivity; people suffer from sunburns within a few minutes of sun exposure. This photosensitivity is generally associated with the appearance of freckles at an early age, especially on the face, neck and arms. These areas may over time look like they have actinic keratoses that are precancerous lesions that have the possibility of becoming squamous cell carcinoma or other types of skin cancers.

Besides skin cancers, XP sufferers are prone to very specific eye cancer such as conjunctiva melanoma and other forms of cancer such as oral cancer, brain tumor and others . There are usually ocular manifestations of the disease which often manifest with these symptoms: photophobia, conjunctivitis, and corneal clouding that results in vision impairment among the patients.