Xeroderma pigmentosum

Last Updated: 2020-11-23

Author(s): Anzengruber, Navarini

Kaposi 1874.

Moonshine disease, XP, Atrophodermia pigmentosa (Crocker), light shrinking skin, Lioderma essentialis congenita (Auspitz).

An autosomal recessive inherited genodermatosis, in which a disruption of the nucleotide excision repair system leads to the development of multiple tumors, premature aging, neurological and ocular diseases.

  • Worldwide
  • All races are affected
  • Incidence: 1 / 250,000 per year (Europe)
  • Prevalence: 1/1000000 (worldwide)

  • The parents of XP patients are obligatory mutation carriers in one of the XP genes.

  • Occurs already in childhood, first manifestation between ½ - 1 ½ years

  • Women = men

  • Tumors can show up as early as the second year of life.

  • Depending on the subtype, there is a different enzymatic defect in DNA repair, which leads to an increased sensitivity, especially to UVB. In the course of the disease an accumulation of somatic mutations occurs, which cause cutaneous neoplasia.

  • 7 complementation groups A-G and XP variant (V)

Defect of excision repair cross-complementing 2 gene repair-cross-complementing-4-gene à defect of the endonuclease detection of damaged DNA disturbedXP-G13q33defect of the endonuclease detection of damaged DNA disturbedXP-V6p21defect of the DNA polymerase ƐDefekt post-replication repair of DNA damage

Repair proteins

Gene locus

 Malfunction Function
XP-A 9q22

DNA damage binding protein 1

 Detection of damaged DNA disturbed
XP-B 2q21 Defect of the excision repair cross-complementing 3 gene Defective helicase
XP-C 3p25

Defect of endonucleases

 Detection of damaged DNA disturbed
XP-D 19q13

Defect of the excision repair cross-complementing 2 gene

Defective helicase
XP-E 11p12

Defect of DNA-damage binding protein 2

Detection of damaged DNA disturbed
XP-F 16ß13

Defect of the excision repair cross-complementing 4 gene; a defect of endonuclease

Detection of damaged DNA disturbed
XP-G 13q33

Defect of the endonuclease

Detection of damaged DNA disturbed
XP-V 6p21

Defect of the DNA polymerase Ɛ

Defective post-replication repair of DNA damage

 

 

  • Neurological changes
    • Approximately 20% of patients with DeSanctis-Cacchione Syndrome [1932]
    • Patients in complement group A

      • Dwarfism

      • Severe mental retardation

  • Ocular changes
    • Approximately 40% have keratoconjunctivitis with photophobia, corneal ulceration, ocular neoplasia.
  • XP-A

    • Dermatological symptoms ↑↑↑

    • In most cases, the development of spinocellular carcinomas occurs

    • Neurological symptoms ↑↑

    • Ocular symptoms ↑↑

  • XP-B

    • Dermatological symptoms ↑↑↑

    • In most cases, the development of basal cell carcinomas and spinocellular carcinomas occurs

    • Neurological symptoms ↑

    • Ocular symptoms ↑↑

  • XP-C

    • Dermatological symptoms ↑

    • In most cases, the development of basal cell carcinomas and spinocellular carcinomas occurs

    • Neurological symptoms ↑

    • Ocular symptoms -

  • XP-D

    • Dermatological symptoms ↑

    • In most cases, malignant melanomas are present

    • Neurological symptoms ↑↑

    • Ocular symptoms ↑

  • XP-E

    • Dermatological symptoms ↑

    • In most cases, basal cell carcinomas are present

    • Neurological symptoms -

    • Ocular symptoms -

  • XP-F

    • Dermatological symptoms ↑↑

    • In most cases, basal cell carcinomas and spinocellular carcinomas are present

    • Neurological symptoms ↑

    • Ocular symptoms -

  • XP-G

    • Dermatological symptoms ↑↑

    • In most cases, basal cell carcinomas and spinocellular carcinomas are present

    • Neurological symptoms ↑

    • Ocular symptoms -

  • XP-V
    • Dermatological symptoms ↑

    • In most cases, basal cell carcinomas are present

    • Neurological symptoms -

    • Ocular symptoms -

  • Medical history

    • UV sensitivity (sunburns)

  • Clinical diagnosis

  • Laboratory
    • Determination of complementation types

      • Detection of the absence of an endonuclease in fibroblast culture

  • In specialized centers:

    • Measurement of fibroblast survival post-UV exposure

    • Measurement of DNA repair capacity

    • Prenatal diagnosis in specialized laboratories

Particularly in sun-exposed areas.

  • Increased or reduced melanin retention (stratum basale, dermal pigment incontinence)

  • Solar elastosis

  • Telangiectasia

  • Changes according to actinic keratoses, BCC, SCC and MM (in XP-D)

Acitretin (Neotigasone®) p.o.

  • Initial: 0.5 mg / kg BW once a day
  • Maintenance dose: 0.1-0.2 mg / kg BW 1x per day
  • Isotretinoin p.o. 0.5-2 mg 1x per day

Surgical measures

  • In case of the occurrence of cutaneous neoplasia
     
Therapy of 1st choice by Lebwohl  

Evidence level
UV protection   C

Excision of cutaneous neoplasia

   C
     
Therapy of 2nd choice by Lebwohl  
Imiquimod (topical)   B
5-Fluorouracil   B
Oral Retinoids   C
     

Therapy of 3rd choice by Lebwohl

    

Resurfacing/dermabrasion/chemical peels

   E

 

·         UV protection (risk of skin cancer is 1000 times higher)

·         Genetic counseling

·         Psychological care

·         No nicotine consumption (the pulmonary immunological repair mechanisms are also disturbed here)

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