Clinical Features, Genetics and Treatment in a Russian Cohort of Young Patients with Xeroderma Pigmentosum: A Single Center Experience

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are rare autosomal recessive DNA repair disorders. XP is characterized by extreme sensitivity to UV-radiation and a very high risk of skin cancer. To date, little is known about the clinical characteristics and genetic basis of these diseases in Russia. Here, we present a detailed study of 14 patients (aged 5–30 years) from 11 unrelated families of diverse ethnic backgrounds. Using a multigene panel or whole-genome sequencing, we identified homozygous or compound heterozygous variants in XPC (8 patients) and XPA (3 patients). In one family with two XP cases, a patient with CS and compound heterozygous ERCC6 variants was identified. In total, 110 family members were screened to determine their carrier status. Skin cancer was revealed in 12/13 (92%) of XP patients, with a median age at diagnosis of 12.5 years (range 5–22). Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma developed in 10, 6, and 3 patients, respectively. All three cancer types occurred in 2 patients. All patients underwent surgical treatment; additionally, two patients with BCC received targeted therapy (vismodegib, sonidegib). Anti-PD-1 immunotherapy was administered with a favorable clinical response in three patients with advanced SCC or melanoma.