Clinical manifestation and genetic analysis of familial rare disease genodermatosis xeroderma pigmentosum

Abstract

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by hypersensitivity of the skin to ultraviolet radiation and other carcinogenic agents. This ailment is characterized by increased photosensitivity, skin xerosis, early skin aging, actinic keratosis, erythematous lesions, and hyperpigmentation macules. In this serial case report, we presented four cases with XP from two families in Indonesia. Both families were referred from rural referral health centers, and each family has two affected siblings. They had freckle-like pigmentation on the face, trunk, and extremities, which progressed since childhood. One patient of family 2 died because of an infectious disease. Histopathological examination using cytokeratine (CK), CD10, and Ber-EP4 staining from available tissue biopsy of one affected case of family 1 identified basal cell carcinoma (BCC) on the cheek and melanoma on the right eye. Mutation analysis found ERCC2, c2047C>T and XPC, c1941T>A in the first and second families, respectively. We suppose that this is the first case report of XP in Indonesia that incorporates clinical examination, genetic analysis, and extensive histopathological examination, including immunohistochemistry staining, and a novel pathogenic variant of XPC was found in the second family.

Xeroderma Pigmentosum with Simultaneous Cutaneous and Ocular Squamous Cell Carcinoma

“…Moreover, the incidence is genetically determined and increases with consanguinity. 2 The only one case of XP in Indonesia was reported by Yuniati et al 4 They reported a novel pathogenic variant of XPC, c1941T>A that was found in the second family. 4 To date, there has not been any specific XP gene mutation research in Indonesia yet.…”

“…2 The only one case of XP in Indonesia was reported by Yuniati et al 4 They reported a novel pathogenic variant of XPC, c1941T>A that was found in the second family. 4 To date, there has not been any specific XP gene mutation research in Indonesia yet. Gene mutation testing and family counseling could help in early detection and determine various clinical manifestations.…”

“…7 New advances in molecular biology strategy, such as next-generation sequencing (NGS) used by Yuniati et al, could lead to early diagnosis, but they are still scarce. 4 In this case, gene mutation testing has not been carried out, due to its unavailability in Indonesia and needs to be sent abroad, hence it is very costly.…”

“…2 This condition results in pigmentation changes and the formation of carcinogenic photoproducts, which leads to skin cancers. 2,4 The prevalence of XP is about 1: 250,000 worldwide, 5 and this disease is known as one of the predisposing factors for cutaneous malignancy. The risk of cutaneous malignancy increases 10,000-fold in areas exposed to UV light.…”

Xeroderma pigmentosum: an updated review

“…20 Actinic keratoses are observed at an early age, and actinic cheilitis is not uncommon. 11,23,39 The anterior parts of the eye (conjunctiva, lens, cornea and eyelids) are particularly susceptible to damaging effects of UVR in patients with XP. 6,40 The posterior parts of the eye are protected by the lens which acts as a barrier to UVR.…”