Case Report: PTCH1 Splice-Site Mutation and Sonidegib Treatment in Gorlin-Goltz Syndrome: Clinical Insights from a Family Case Study

This case report discusses a three-generation family with Gorlin-Goltz syndrome, where a heterozygous PTCH1 splice-donor variant was identified as the genetic cause. A minigene splicing assay confirmed exon 20 skipping, indicating a loss-of-function mechanism. Two affected family members with basal cell carcinoma (BCC) were treated with sonidegib for 6 months, using different dosing schedules (200 mg daily vs. 200 mg every other day). Both patients experienced regression of BCC lesions, but daily dosing led to side effects like dysgeusia and alopecia, while every-other-day dosing was better tolerated. The study emphasizes the importance of functional assays for PTCH1 variants and suggests personalized sonidegib dosing to manage toxicity in Gorlin-Goltz syndrome patients.