Xeroderma Pigmentosum

Abstract

Xeroderma pigmentosum (XP) is a rare disorder of defective UV-radiation induced damage repair that is characterized by photosensitivity with easy skin burning following minimal sun exposure, early freckling and development of lentiginous pigmentation along with other features of poikiloderma and a propensity for developing skin cancer at an early age. In this short review, the clinical, pathological, genetic and molecular aspects of XP are reviewed in the current literature. XP encompasses a spectrum of disease that overlaps with other diseases of DNA repair systems. In addition to cutaneous complications, patients are susceptible to eye conditions, neurodegenerative processes, central nervous system tumors and other tumors as a result of UV radiation exposure and its byproducts. Patients with XP frequently experience a shorter life span due to skin cancer and neurodegenerative sequelae, but aggressive preventative measures to minimize UV radiation exposure and damage can improve the course of disease and prolong life. The disease has served as a model for photoaging and UV radiation-induced cancer and has led to a better understanding of cell processes that prevent development of these disease features in normal individuals.

Neurological manifestations of xeroderma pigmentosum due to XPA gene mutation

“…Its prevalence is around 1:250 000 in the USA and Europe 1. There are at least eight different associated genes: subtypes A, B, C, D, E, F, G and XPV 1…”

“…Neurological involvement occurs in around 25% of patients and may include variable degrees of ataxia, cognitive impairment, neuropathy and sensorineural hearing loss 1 2. Xeroderma pigmentosum is also a major risk factor for skin and brain tumours 1. Neuroimaging features may include diffuse cortical atrophy and white matter changes 1 2 Table 1.…”

“…Xeroderma pigmentosum is a group of rare autosomal recessive disorders characterised by skin sensitivity to ultraviolet light, a higher frequency of skin cancers, and abnormal skin pigmentation 1. Several neurological symptoms are described in xeroderma pigmentosum 2.…”

Interplay between BRCA1 and GADD45A and Its Potential for Nucleotide Excision Repair in Breast Cancer Pathogenesis

“…Defects in NER can be attributed to several hereditary human diseases, including xeroderma pigmentosum (XP). XP, an autosomal recessive genetic disorder, is characterized by increased sensitivity to UV, resulting in skin cancers underlined by a decreased efficacy to repair UV-induced photoproducts [42]. The great majority of XP cases are associated with mutations in NER genes involved in the recognition and excision of UV-related photoproducts.…”

Xeroderma pigmentosum: overview of pharmacology and novel therapeutic strategies for neurological symptoms

“…This may manifest with severe skin burning and blistering in infants, but not all patients exhibit this acute abnormal reaction to sunlight (DiGiovanna and Kraemer, ; Sethi et al, ; Fassihi et al, ). Freckling‐like skin changes, however, develop in all patients and eventually progress into atrophy, telangiectasias and intermixed hypo‐ and hyperpigmented areas (Black, ). Premalignant lesions, such as actinic keratoses and skin neoplasms in sun‐exposed areas, are observed at an early age and are related to complementation group (DiGiovanna and Kraemer, ).…”