6.1.2 Xeroderma Pigmentosum

Grading & Level of Importance: C

Review:

2026

W. Burgdorf, Munich; J. McGrath, London
Revised by C.C. Zouboulis, Dessau

Overview:

ICD-11
Synonyms
Epidemiology
Definition
Aetiology & Pathogenesis
Signs & Symptoms
Localisation
Classification
Laboratory & other workups
Dermatopathology
Course
Complications
Diagnosis
Differential Diagnosis
Prevention & Therapy
Special

ICD-11

LD27.1

Synonyms

Epidemiology

From about 1 in 500,000 live births in Western Europe to much higher frequencies in Japan and North Africa.

Definition

Group of uncommon genodermatoses with markedly increased light sensitivity and tendency towards developing actinic damage and malignant skin tumours.

Aetiology & Pathogenesis

Autosomal recessive inherited defects in DNA excision repair enzymes. Cells cannot repair UV-induced damage.

Autosomal recessive inherited defects in DNA excision repair enzymes (NER; Groups XPA to XPG). Cells cannot repair UV-induced damage. The group XPV exhibits defective translesion DNA synthesis because of mutations in the POLH gene encoding DNA polymerase η.

Signs & Symptoms

Marked photosensitivity with acute photodermatitis and marked actinic damage, multiple lentigines, including actinic keratoses, squamous cell carcinomas, basal cell carcinomas, malignant melanomas, poikiloderma, skin atrophy. Eyes also suffer UV damage. Some types (DeSanctis-Cacchione syndrome) have neurological findings.

Wide variety of clinical features with marked photosensitivity with acute photodermatitis and marked actinic damage, including actinic keratoses, squamous cell carcinomas, basal cell carcinomas, malignant melanomas, poikiloderma and skin atrophy. Eyes also suffer UV damage. Some types (DeSanctis- Cacchione syndrome) have neurological findings. Individuals in which NER remains functional (XPC, E and V) have skin and eye (photophobia, pterygia, pingueculae, corneal scarring and ocular surface cancers) defects but no significant neurological problems. Individuals with affected NER may additionally have neurological abnormalities (progressive neurological degeneration with peripheral neuropathy, sensorineural hearing loss, impaired cognition and declining gait) in addition to severe and exaggerated sunburn reactions.

Localisation

Generalised; visible symptoms in UV light-exposed areas.

Classification

Types A-G dependent on type of gene defect.

Types A-G. Splicing mutations in XPA and XPD and a specific amino acid change in XPD are associated with mild phenotypes. The XP-F group has reduced pigmentation changes and a lower susceptibility to skin cancer than XPs in other groups.

Laboratory & other workups

Identification of endonuclease and other repair enzyme defects in cultured fibroblasts, DNA sequencing of known genes.

Dermatopathology

According to light induced skin damage and type and stage of tumor.

Corresponds to solar lentigines, showing atrophy of the epidermis and spot-like hyperpigmentation in the stratum basale.

Course

Reduced life expectancy starting already in the first life decade and depending on defect. Development of multiple malignant skin tumours, especially squamous cell carcinomas and malignant melanomas.

Complications

Development of malignant skin tumours (squamous cell carcinoma, basal cell carcinoma, malignant melanoma) before 20 years of age.

Diagnosis

Clinical findings (photosensitivity, early actinic damage), genetic analysis, family history.

Differential Diagnosis

Xeroderma pigmentosum variants with same phenotype, later onset, no genetic defects (pigmented xerodermoid).

Prevention & Therapy

Consequent avoidance of UV exposure. Early use of high-potency broad-spectrum sunscreens, close clinical control, prompt tumour excision. Systemic retinoids for prophylaxis. Vitamin D supplementation.

Special

Genetic counselling.

XP-C patient with advanced metastatic cancer arising from an angiosarcoma had a dramatic recovery following immunotherapy treatment (after molecular analysis).

Podcasts

Xeroderma pigment