[Xeroderma pigmentosum: children of the moon] <br /><br /> <br /> Xeroderma pigmentosum is a rare disorder; it is estimated to affect about 1 in 1 million people in the United States and Europe. The condition is more common in Japan, North Africa,and the Middle East.It is commonly known as XP and it is an inherited condition characterized by an extreme sensitivity to ultraviolet radiation (UVR), which is present in sunlight and may also be found in some types of artificial lighting. This condition mostly affects the eyes and areas of skin exposed to the sun. Xeroderma pigmentosum is associated with an increased risk of UVR-induced cancers. People with this condition often experience premature aging. Some affected individuals also have problems involving the nervous system.<br />The signs of xeroderma pigmentosum usually appear in infancy or early childhood. About half of affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. However, some children with xeroderma pigmentosum can tan normally. <br />By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name.<br />People with xeroderma pigmentosum are 10,000 times more likely to develop non-melanoma skin cancer and up to 2,000 times more likely to develop melanoma skin cancer compared to individuals without this condition. The types of skin cancer that can develop include basal cell carcinoma, squamous cell carcinoma, and melanoma. Most commonly, the first skin cancer appears in affected individuals before age 10. <br />Without protection from the sun and other sources of UVR, most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on portions of the body that are exposed to the sun, including the face, the lips, the eyelids, the surface of the eyes, the scalp, and the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of some internal cancers, including brain tumors, thyroid cancer, and blood cancers. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.<br />The eyes of people with xeroderma pigmentosum may be painfully sensitive to UVR (photophobia). If the eyes are not protected from UVR, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of cancer on the surface of the eye, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.<br />About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time.Individuals with xeroderma pigmentosum may experience early menopause.<br /> <br />Causes : Xeroderma pigmentosum is caused by variants (also called mutations) in at least nine genes: DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, and XPC. These genes are involved in repairing damaged DNA. DNA can be damaged by UVR and by toxic chemicals, such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems. However, in people with xeroderma pigmentosum, DNA damage is not repaired normally. As damage builds up in DNA, cells malfunction and eventually become cancerous or die.<br />Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER). The proteins produced from these genes play a variety of roles in this process. They recognize DNA damage, unwind regions of DNA where the damage has occurred, snip out (excise) the abnormal sections, and replace the damaged areas with the correct DNA. Changes in NER-related genes prevent cells from carrying out one or more of these steps. The DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, and XPC genes are all involved in the NER process. The POLH gene also plays a role in protecting cells from UVR-induced DNA damage by bypassing the DNA damage, although it is not involved in NER. <br />Signs and symptoms of XP:<br />People with XP can have some, or all, of these signs and symptoms.<br />• Burning easily in the sun, no matter what the colour of your skin.<br />• Freckles from an early age (under 2 years) in areas exposed to daylight.<br />• Eye sensitivity to bright light (photophobia).<br />• Eye-surface cancers.<br />• Skin cancers.<br />• Skin ageing.<br />• Nerve or brain (neurological) problems, such as hearing loss, poor balance, poor memory or learning problems.<br />Managing XP : <br />Although it is a lifelong condition, there are ways to manage XP.<br />-Ultraviolet radiation (UVR) protection<br />It is important to keep skin and eye damage to a minimum. If you do not protect yourself from UVR, freckling can get worse. The chance of getting skin cancers is also much higher.<br />Regular skin checks (usually every 3 to 6 months) can find any signs of skin cancers early so that they can be treated more quickly. If we do not find these cancers early, they can get larger. A larger cancer causes more scarring if we remove it with surgery.If cancer is not found early, this can be life-threatening because it might have spread to other organs.<br />-Vitamin D levels<br />Most people with XP have a low vitamin D level because they need to protect their skin from daylight.<br />Blood tests can check your vitamin D levels. If your level is low, we can give you vitamin D supplements. Otherwise, there is a chance that your bones will get weaker.<br />-Regular tests<br />It's important to find any problems early and get support.<br />If you have an eye test at least every year, this can find any eyesight problems. You can then have suitable treatments, such as eye drops, glasses, or a biopsy of any areas of concern in the eye.<br />A neurological assessment can find any brain or nerve problems. We examine you and sometimes do hearing tests, nerve conduction studies (tests to find out how well your nerves are working) and an MRI scan.<br />-Emotional (psychological) support<br />You can speak to a psychologist if you need support to manage your XP and cope with your diagnosis.<br /><br />