Consider xeroderma pigmentosum (XP) in a young child (typically <2 years old) with early-onset severe and exaggerated sunburn with minimal sun exposure or with early and extensive freckle-like lesions (lentigines) in sun-exposed areas.
Patients aged <20 years have a more than 1000-fold increased risk of cutaneous malignancies. Acute and chronic ocular symptoms (e.g., photophobia and dry eyes due to conjunctival xerosis, respectively) are present in 40% to 90% of patients.
Adults presenting with XP tend to be aged between 20 and 40 years with numerous premalignant or malignant skin cancers.
Diagnosis is clinical. Unscheduled DNA synthesis testing and genetic testing, where available, confirms the diagnosis and the subtype.
Strict and consistent ultraviolet radiation and daylight protection and avoidance is the mainstay of treatment. Early management of premalignant and malignant skin and ocular lesions improves survival.
Around 25% of patients experience progressive and irreversible neurologic degeneration (e.g., sensorineural hearing loss, cognitive impairment). Supportive care can be provided in the form of hearing aids, speech therapy, and physical and occupational therapy.
Follow-up for cutaneous and ocular malignancies is recommended in all patients every 3-6 months. For patients with neurologic disease, regular follow-up by neurology and otorhinolaryngology is recommended.
Xeroderma pigmentosum (XP) is a rare autosomal recessive inherited disorder of DNA repair predominantly characterized by extreme sensitivity to ultraviolet radiation exposure, pigmentary skin changes (lentigines), ocular changes, highly increased predisposition to skin cancers, and, in some patients, progressive neurodegeneration.
History and exam
Key diagnostic factors
- presence of risk factors
- prominent conjunctival injection
- excessive freckle-like skin pigmentation (lentigines)
- skin xerosis
- skin atrophy
- skin wrinkling
- skin telangiectasia
- signs of skin cancer
- corneal neovascularization
- dry eye
- keratitis/corneal scarring
- conjunctival melanosis
- signs of malignancy over the lids, conjunctiva, or cornea
- diminished or absent deep tendon stretch reflex
- sensorineural deafness
- cognitive impairment
- acquired microcephaly
- other neurodegenerative manifestations
- age <2 years
- positive family history
- parental consanguinity
- Japanese ancestry
1st investigations to order
- clinical diagnosis
Investigations to consider
- unscheduled DNA synthesis
- genetic testing
- comprehensive genomic testing
- Cerebro-oculo-facio-skeletal syndrome (COFS)
- Cockayne syndrome
- Xeroderma pigmentosum clinical practice guidelines
- Recommendations for childhood cancer screening and surveillance in DNA repair disorders
Skin cancer (squamous cell)
Basal cell carcinomaMore Patient leaflets
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