Xeroderma Pigmentosum: General Aspects and Management

Abstract

Xeroderma Pigmentosum (XP) is a rare genetic syndrome with a defective DNA nucleotide excision repair. It is characterized by (i) an extreme sensitivity to ultraviolet (UV)-induced damages in the skin and eyes; (ii) high risk to develop multiple skin tumours; and (iii) neurologic alterations in the most severe form. To date, the management of XP patients consists of (i) early diagnosis; (ii) a long-life protection from ultraviolet radiation, including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of topical sunscreens; and (iii) surgical resections of skin cancers. No curative treatment is available at present. Thus, in the last decade, in order to prevent or delay the progression of the clinical signs of XP, numerous strategies have been proposed and tested, in some cases, with adverse effects. The present review provides an overview of the molecular mechanisms featuring the development of XP and highlights both advantages and disadvantages of the clinical approaches developed throughout the years. The intention of the authors is to sensitize scientists to the crucial aspects of the pathology that could be differently targeted. In this context, the exploration of the process underlining the conception of liposomal nanocarriers is reported to focus the attention on the potentialities of liposomal technology to optimize the administration of chemoprotective agents in XP patients.

Skin Conditions and Movement Disorders: Hiding in Plain Sight

“…Xeroderma pigmentosum (XP) is an autosomal recessive disorder with 100% penetrance, characterized by enzymatic defect in DNA repair pathway known as nucleotide excision repair (NER) and a combination of cutaneous, ophthalmological and neurological symptoms. Depending on the involved genes, complementation groups from XP‐A to XP‐G and XP‐V have been described 71 . Patients with XP typically show extreme hypersensitivity to UV exposure with sunburns often occurring from early infancy (60% of infant cases after minimal UV exposure), skin xerosis (dryness), progressive freckle‐like pigmentary changes (often prominent already around 2 years of age), progeroid skin changes and an increased incidence of skin malignancies (Fig.…”

“…Depending on the involved genes, complementation groups from XP-A to XP-G and XP-V have been described. 71 Patients with XP typically show extreme hypersensitivity to UV exposure with sunburns often occurring from early infancy (60% of infant cases after minimal UV exposure), skin xerosis (dryness), progressive freckle-like pigmentary changes (often prominent already around 2 years of age), progeroid skin changes and an increased incidence of skin malignancies (Fig. 2A, B).…”

“…2A, B). 71 Skin cancer usually occurs in the face/head/neck area and compared to healthy population may be increased 2000‐fold for cutaneous melanoma and up to 10,000‐fold for squamous cell and basal cell carcinomas 72 . In addition to cutaneous manifestation, ophthalmological symptoms may include ocular surface pathology, eyelid damage, and ophthalmic malignancies.…”

Xeroderma pigmentosum: an updated review

“…Certain types of XP are more prone to ocular disease and progressive neurodegeneration, dependent on the causative mutation. 4,5 Early recognition of XP is important so that avoidance and protection from UVR can be initiated early to minimize the complications arising from the harmful effects of UVR.…”

Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum

“…Xeroderma pigmentosum (XP) is a rare genetic autosomal recessive syndrome, characterized by an enzymatic defect in the DNA-repair pathway known as nucleotide excision repair (NER). [ 1 ] NER is involved in the removal of bulky adducts induced by the ultraviolet component of sun-light or other environmental carcinogens. Alteration in this pathway results in several rare diseases characterized by a wide spectrum of clinical features with photosensitivity as a common trait.…”