Gorlin Syndrome — SCE Dermatology MCQ

Correct answer: E — PTCH1 (Patched-1)

The correct answer is E, PTCH1 (Patched-1). This man's presentation, multiple BCCs from an unusually young age, jaw keratocysts, palmar pits and an autosomal dominant family history, is classic for Gorlin (basal cell naevus) syndrome, which is caused by a germline mutation in PTCH1, a tumour suppressor gene encoding the Hedgehog pathway receptor on chromosome 9q22. Loss of PTCH1 function removes its inhibitory brake on Smoothened, causing constitutive Hedgehog signalling that drives basaloid proliferation, odontogenic keratocyst formation and palmar/plantar pitting. The combination of early multiple BCCs plus jaw cysts plus palmar pits plus a similarly affected first degree relative fulfils recognised diagnostic criteria for this autosomal dominant disorder, making PTCH1 the discriminating answer rather than any sporadic BCC or melanoma pathway gene. Why the other options are wrong: C. RB1: This causes retinoblastoma and predisposes to osteosarcoma, not BCCs, jaw cysts or palmar pits. D. TP53: Mutated in Li-Fraumeni syndrome, associated with sarcomas, breast cancer and adrenocortical carcinoma, not the jaw cyst and palmar pit phenotype described. B. BRAF V600E: This is a somatic driver mutation seen in sporadic melanoma and some other tumours, not a heritable germline cause of a multisystem syndrome with jaw keratocysts. A. CDKN2A: Mutations here cause familial atypical multiple mole melanoma syndrome, presenting with dysplastic naevi and melanoma, not odontogenic keratocysts or palmar pits. Key point: Multiple early onset BCCs with jaw keratocysts and palmar pits in an autosomal dominant pattern points to Gorlin syndrome from PTCH1 mutation causing dysregulated Hedgehog signalling.

Reference: Verkouteren JAC et al. A guideline for the clinical management of basal cell naevus syndrome (Gorlin-Goltz syndrome). British Journal of Dermatology 2022;186(2):215-226. https://academic.oup.com/bjd/article/186/2/215/6599271