## Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome) **Key Point:** Gorlin syndrome is an autosomal dominant disorder caused by PTCH1 gene mutations (tumor suppressor gene in the Hedgehog signaling pathway) that leads to multiple BCCs, often in childhood or young adulthood. ### Gorlin Syndrome: Clinical Features **Mnemonic:** **GORLIN** = **G**enetic predisposition, **O**dontogenic keratocysts, **R**ibs (bifid/fused), **L**ipomas, **I**ncreased BCC, **N**asal/skeletal abnormalities **High-Yield:** Key diagnostic criteria include: - Multiple BCCs (often > 10 by age 40) - Odontogenic keratocysts of the jaw (pathognomonic) - Skeletal abnormalities (bifid ribs, kyphoscoliosis, frontal bossing) - Palmar/plantar pits (punctate depressions) - Macrocephaly with frontal bossing - Increased risk of medulloblastoma, ovarian fibromas, and other malignancies ### Comparison with Other Hereditary Cancer Syndromes | Syndrome | Gene | Key Features | BCC Risk | |----------|------|--------------|----------| | **Gorlin** | PTCH1 | Multiple BCCs, odontogenic keratocysts, skeletal abnormalities | Very high (100%) | | **Xeroderma pigmentosum** | XPA–XPG (nucleotide excision repair) | Photosensitivity, severe sun sensitivity, SCC > BCC | High (SCC predominant) | | **Cowden** | PTEN | Hamartomas, breast/thyroid cancer, mucosal papules | Mild BCC risk | | **Muir-Torre** | MLH1/MSH2 | Sebaceous tumors, colorectal cancer | Minimal BCC risk | **Clinical Pearl:** Gorlin syndrome patients require lifelong surveillance, sun protection, and regular dermatologic screening. Genetic counseling and testing of family members is essential given the autosomal dominant inheritance pattern. ### Pathophysiology PTCH1 is a negative regulator of the Hedgehog (Hh) signaling pathway. Loss-of-function mutations lead to constitutive activation of Hh signaling → uncontrolled basal cell proliferation → multiple BCCs. 
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