What Is Xeroderma Pigmentosum?
Xeroderma pigmentosum is an inherited disorder characterized by an extreme sensitivity to UV (ultraviolet) rays of the sunlight. It mostly affects the eyes and areas of sun-exposed skin surfaces like the face, eyelids, and lips. It may also affect the nervous system.
How Is It Otherwise Known As?
It is also known by the following names:
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De Sanctis-Cacchione syndrome.
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XP.
Who Gets Xeroderma Pigmentosum?
Couples who are carriers of the xeroderma pigmentosum trait have a greater risk of having the first child with xeroderma pigmentosum, and there is a 25 % chance of having the next child with xeroderma pigmentosum. Xeroderma pigmentosum is widespread and affects men and women of all ages and races. It is more common in Japan.
What Are the Causes of Xeroderma Pigmentosum?
Xeroderma pigmentosum is caused by mutation of genes that repair the damage in the DNA. DNA is damaged by the sun’s UV rays and toxic chemicals found in cigarettes and other smoking items. Normal cells usually fix the DNA damage before any problem arises. In xeroderma pigmentosum patients, DNA damage is not repaired normally. As more damages occur in DNA, there is improper functioning of cells, and ultimately it becomes cancerous or dies.
The two genes that are involved in xeroderma pigmentosum are nucleotide excision repair (NER) and the POLH gene. The NER gene repairs and replaces the DNA structure's damage, whereas the POLH gene protects cells from UV-induced DNA damage. Inherited NER-related genes or POLH gene anomalies can result in xeroderma pigmentosum. The main characteristic of xeroderma pigmentosum is the stacking up of unrepaired damaged DNA. When a gene gets damaged by UV rays cells either grow too fast uncontrollably or die. Uncontrolled cell growth leads to the development of cancer and neurological abnormalities.
What Are the Symptoms of Xeroderma Pigmentosum?
Xeroderma pigmentosum progresses in three stages.
- The first stage starts around six months after birth. Sun-exposed areas such as the face start reddening with scales and freckles. Irregular dark spots also begin to appear and progress to the neck, lower legs, and even to the trunk in severe cases. These skin changes diminish in cold climates.
- Continuous sun exposure advances to the second stage, characterized by skin atrophy, poikiloderma, telangiectasia, mottled hyperpigmentation, and hypopigmentation.
- In the third stage, actinic keratosis and skin cancers like basal cell carcinoma, squamous cell carcinoma, and melanoma develop. It commonly occurs between four to five years, with a mean age of eight years. They are predominant in sun-exposed areas such as the face. Cancer can develop on the scalp, eyes, tip of the tongue, or brain tumors. Additionally, xeroderma pigmentosum-affected individuals who are smokers significantly increase the risk of lung cancer.
- Nearly 80 % of xeroderma pigmentosum patients develop eye problems. When exposed to the sun (photophobia), features like painful eyes and irritated, bloodshot, and cloudy eyes are common. Conjunctivitis might occur. Non-cancerous and cancerous growths may occur in the eyes.
- About 20 % of xeroderma pigmentosum patients experience neurological problems. They range from mild to severe and include poor coordination, developmental delay, spasticity, deafness, short stature, loss of intellectual function, difficulty in swallowing, talking, and walking, and seizures. It may occur in late childhood or adolescence and tends to worsen over time.
What Are the Variants of Xeroderma Pigmentosum?
At present, there are at least eight genetic forms of xeroderma pigmentosum. Complementation group A (XP-A) to complementation group G (XP-G) and a variant type (XP-V). The types are differentiated by their genetic cause. All these types increase the risk of skin cancer, while some are more likely to be associated with neurological abnormalities.
How Is Xeroderma Pigmentosum Diagnosed?
Xeroderma pigmentosum is usually diagnosed in early infancy, around one or two years of age. A severe sunburn after the child's first sun exposure may indicate the diagnosis of xeroderma pigmentosum. Evaluating the DNA repair factor from skin or blood samples can confirm xeroderma pigmentosum. Molecular genetic testing is done to confirm mutations of the xeroderma pigmentosum genes.
What Is the Treatment for Xeroderma Pigmentosum?
There is no known cure for xeroderma pigmentosum. The aim of the treatment is sun avoidance. It includes UV protection from the sun and unshielded fluorescent lamps.
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Restrict outdoor activities to night-time and stay indoors during the day.
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Wear protective clothing with long sleeves and pants, tightly woven fabrics, and a wide hat.
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Protect eyes with UV–absorbing sunglasses.
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Apply broad-spectrum sunscreens with SPF 50 or greater generously to all sun-exposed areas.
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Gene therapy for xeroderma pigmentosum is still in the investigational stage.
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Actinic keratosis can be treated with cryotherapy or 5-Fluorouracil topical cream.
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Isotretinoin, a derivative of vitamin A, may be prescribed to prevent cancer by altering keratinocyte differentiation.
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Skin cancers, when developed, are usually excised.
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Frequent eye checkup by an ophthalmologist and neurological problems by a neurologist is recommended.
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Patients should undergo skin examinations by a skin specialist every three to six months.
How to Prevent Xeroderma Pigmentosum?
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Avoid consanguineous marriage in family members and known carriers of xeroderma pigmentosum.
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Prenatal fetus diagnosis with risk of xeroderma pigmentosum by amniocentesis or chorionic villi sampling and chromosomal breakage studies should be made.
What Are the Complications of Xeroderma Pigmentosum?
People with xeroderma pigmentosum have an almost 100 % risk of developing skin cancers if the environment is not consciously controlled. Skin cancer is diagnosed commonly in childhood. There is an increased risk of developing cancer in the eyes, lips, and mouth, along with other neurologic problems.
What Is the Prognosis of Xeroderma Pigmentosum?
The prognosis of xeroderma pigmentosum is usually bad. Many xeroderma pigmentosum patients die at an early age from skin cancers. However, when diagnosed early, with mild neurological symptoms, proper precautionary measures like avoiding exposure to UV light may increase the survival rate beyond middle age.
Conclusion:
Xeroderma pigmentosum is a genetic multisystem disorder characterized by an increased sensitivity to the sun’s ultraviolet radiation damaging the DNA. It is seen in sun-exposed body areas, with the greatest effect on the skin, eyes, and surrounding tissues. XP patients develop progressive neuro-degeneration, skin cancer, and cancer of the eye and its surrounding tissues. These symptoms appear early in life, before ten years of age. Xeroderma pigmentosum is managed by preventative techniques and regular screening for skin changes, vision, and neurologic status. Most symptoms are treated with medication or surgery, but some neurologic problems and cancers can be life-threatening.
