Clinicopathological Study of Xeroderma Pigmentosa: A Series of Eight Cases

Abstract

Abstract Background: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease, resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR)-induced DNA damage in the nucleotide excision repair pathway. This results in increased photosensitivity, UVR-induced damage to skin and eye, increased susceptibility to cutaneous and ocular cancers, and progressive neurodegeneration in some patients. Aims and Objective: The objective of the study was to describe the clinicopathological spectrum of eight cases of XP. Materials and Methods: An ambispective case series was conducted in a pediatric tertiary care hospital in eastern India during a 10-year period from 2013 to 2022. Results: All the children of our cohort were born of consanguineous marriage. The mean age of presentation was 1.2 years (range: 7 months–3 years), whereas three children presented during their infancy. The male-to-female ratio was 5:3. The most common findings were cutaneous (100%), followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme photosensitivity followed by abnormal skin pigmentation and subsequently progressive xerosis, atrophy, wrinkling, and poikiloderma over time. Six patients had varied degrees of ocular involvement, whereas three of them had severe manifestations including madarosis, tylosis, ectropion, lagophthalmos, phthisis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. Fifty percent (n = 4) of cases had cutaneous and ocular premalignant (actinic keratosis) and malignant lesions including melanoma and nonmelanoma skin cancer such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Neurological abnormalities (subnormal intelligence) were found in two cases. There was no evidence of sensory neural hearing loss, microcephaly, neuroregression, or neurodeficits. Conclusion: Although XP is associated with increased mortality and morbidity, early diagnosis followed by persistent vigorous photoprotection and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Besides genetic counseling, further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.