Conditions · Metabolism (biochemistry)
Xeroderma pigmentosum !
An inherited disease in which skin cannot repair sun damage: easy burns, freckles and skin cancers from childhood.
Updated 2026-11-01
Structures involved
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In biochemistry
Why it happens
- Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum
- Radiation and cancer: ultraviolet and ionizing
- Hereditary cancer syndromes: the table to know
- Ionizing radiation injury
What it is
An autosomal recessive defect of nucleotide excision repair (genes XPA to XPG, POLH) that leaves UV-induced pyrimidine dimers uncorrected.
Who gets it
Rare: about 1 in a million people in the United States and Europe, more common in Japan, North Africa and the Middle East. It is more common when parents are related. No published figures for Colombia.
Causes
- Biallelic variants in nucleotide excision repair genes (XPA, ERCC2/XPD, XPC, ERCC4/XPF, ERCC5/XPG, DDB2) or in POLH (XP variant)
- Autosomal recessive inheritance
Risk factors
- Carrier or related parents
- Unprotected sun exposure (triggers the damage)
Pathophysiology
UV light joins two neighbouring pyrimidines (cyclobutane dimers and 6-4 photoproducts). Normally the NER pathway detects the distortion, cuts out a stretch of about 30 nucleotides and replaces it. In XP the pathway fails: the lesions persist, replication copies them with errors (UV-signature C→T mutations in genes such as TP53) and skin cancers arise thousands of times more often than in the general population. In groups XPA, XPB, XPD and XPG, neurons accumulate unrepaired oxidative damage and degenerate. In the XP variant, polymerase η, which normally copies dimers accurately, is missing.
Classification
- Complementation groups XP-A to XP-G by affected gene
- XP variant (POLH): normal repair, failed translesion synthesis
- With or without neurological involvement
Symptoms and signs
- Severe sunburn after minimal exposure in infancy (in many groups)
- Many freckles on exposed areas before age 2
- Dry, thin skin with light and dark patches (poikiloderma)
- Photophobia, red eyes, keratitis and corneal clouding
- Skin cancers (basal cell, squamous cell, melanoma) from childhood
- In some groups: progressive hearing loss, loss of reflexes and cognitive decline
Diagnosis
- Clinical
- A child with extreme photosensitivity, early freckling and early skin lesions; history of consanguinity.
- Tests
- DNA repair study in cultured fibroblasts (unscheduled DNA synthesis after UV irradiation) and sequencing of the XP genes to confirm the group.
- Imaging
- Brain MRI may show atrophy in the neurological forms.
Treatment
- Lifestyle
- Strict protection from ultraviolet light: UV-blocking clothing and glasses, window filters and activities after dark.
- Follow-up
- Skin and eye checks every few months by dermatology and ophthalmology.
- Surgical
- Early removal of precancerous lesions and skin cancers.
- Medical
- Topical treatment of precancerous lesions and vitamin D supplementation because of sun avoidance.
- Rehabilitation
- Hearing and neurological support in the forms with nervous-system involvement.
Complications
- Basal cell and squamous cell carcinoma
- Melanoma
- Blindness from corneal and eyelid damage
- Progressive neurodegeneration in some groups
- Internal tumours (brain, lung in smokers) more often
Prognosis
Without sun protection survival is much shorter because of skin cancer; with strict protection and surveillance many patients reach adulthood. Neurological forms have a worse outlook.
Prevention
- Genetic counselling for affected families
- UV protection from diagnosis
Test yourself
Think of the answer, then tap the question to see it.
Which DNA repair pathway fails in xeroderma pigmentosum?
Nucleotide excision repair (NER), which normally removes UV-induced pyrimidine dimers.
What is the XP variant, and which enzyme causes it?
A form with normal NER in which DNA polymerase η (POLH), which copies thymine dimers accurately, is missing.
Why do some XP patients have neurodegeneration?
In certain groups (XPA, XPD, XPG) neurons accumulate unrepaired DNA damage and die progressively.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Xeroderma pigmentosum: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); XPA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); XPC gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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