Random Dermatology MCQ - Gorlin syndrome

A 22-year-old man presents with two new, pearly, telangiectatic papules on his face that were biopsied and confirmed as basal cell carcinomas (BCCs). His past medical history includes surgical removal of a jaw cyst at age 16. On physical examination, you note multiple small, flesh-colored pits on his palms and soles. A skull X-ray ordered for an unrelated reason reveals lamellar calcification of the falx cerebri. What is the most likely genetic mutation and the most important screening recommendation to reduce mortality in this syndrome?

A. Mutation in the PTCH1 gene; annual echocardiograms to screen for cardiac myxomas.
B. Mutation in the PTCH1 gene; biannual panoramic dental radiographs to screen for odontogenic keratocysts.
C. Mutation in the SUFU gene; annual colonoscopy to screen for colorectal cancer.
D. Mutation in the TP53 gene; annual whole-body MRI to screen for sarcomas.
E. Mutation in the CYLD gene; annual brain MRI to screen for meningiomas.

Correct Answer: B. Mutation in the PTCH1 gene; biannual panoramic dental radiographs to screen for odontogenic keratocysts.

Answer and Explanation

The correct answer is B. This question describes the classic diagnostic criteria for Gorlin syndrome (Nevoid Basal Cell Carcinoma Syndrome). The patient has major criteria: 1) Multiple basal cell carcinomas (often at a young age on non-sun-exposed skin), 2) Odontogenic keratocysts (OKCs) of the jaw, and 3) Palmar/plantar pits. The incidental finding of falx cerebri calcification is another major criterion. The syndrome is caused by mutations in the PTCH1 gene, a tumor suppressor in the Hedgehog signaling pathway. While BCCs are the hallmark, the odontogenic keratocysts are often the earliest presenting feature and can cause significant morbidity (pain, swelling, tooth displacement, pathologic fracture). Therefore, regular screening with panoramic dental radiographs (typically every 12-18 months) is a cornerstone of management to detect and treat OKCs early, preventing destructive complications.

Why the Other Options are Incorrect:

• A. Mutation in the PTCH1 gene; annual echocardiograms...: Cardiac myxomas are a feature of Carney complex, not Gorlin syndrome.

• C. Mutation in the SUFU gene: SUFU is another gene in the Hedgehog pathway where mutations can cause a subset of Gorlin syndrome cases, but the screening priority remains for jaw cysts and BCCs, not colon cancer.

• D. Mutation in the TP53 gene: This causes Li-Fraumeni syndrome, associated with a very different tumor spectrum (sarcomas, breast cancer, brain tumors).

• E. Mutation in the CYLD gene: This causes Brooke-Spiegler syndrome, associated with cylindromas, trichoepitheliomas, and spiradenomas, not BCCs or jaw cysts.

Additional High-Yield Information for Exams:

• Major Diagnostic Criteria: The presence of two major criteria or one major + two minor criteria establishes the diagnosis.

  • Major: >2 BCCs or 1 BCC <20yrs, OKC of jaw, palmar/plantar pits, bilamellar calcification of falx cerebri, first-degree relative with NBCCS.

  • Minor: Rib anomalies, macrocephaly, cleft lip/palate, medulloblastoma (especially desmoplastic subtype), ovarian/cardiac fibromas, lymphomesenteric cysts.

• Tumor Risks:

  • Basal Cell Carcinomas: Hundreds to thousands may develop, accelerated by UV and ionizing radiation.

  • Medulloblastoma: A desmoplastic subtype occurs in ~5% of patients, usually before age 3. This is a major cause of early mortality.

  • Odontogenic Keratocysts: Recur after simple enucleation (~60% rate); require careful surgical management.

• Differential Diagnosis: Conditions with multiple BCCs (e.g., Bazex-Dupré-Christol syndrome, Rombo syndrome) lack the systemic findings like jaw cysts and falx calcification.

• Associated Conditions & Prognosis:

  • Prognosis: Lifespan can be normal with careful management. Major morbidity comes from the cosmetic and functional burden of BCCs, complications from jaw cysts, and, in a subset, medulloblastoma.

  • Radiation Sensitivity: Patients are extremely sensitive to ionizing radiation. Radiation therapy for any condition (including BCCs) can induce hundreds of aggressive BCCs in the field and is contraindicated.

• Management & Rationale:

  • Rationale: A proactive, multidisciplinary approach focusing on prevention, early detection, and avoidance of harmful exposures.

  • First-line/Obligatory Screening:

    1. Neurologic: Brain MRI in early childhood (0-3 years) to screen for medulloblastoma.

    2. Dental: Panoramic radiographs every 12-18 months from age 8 until the mid-40s to screen for OKCs.

    3. Dermatologic: Regular total-body skin exams (every 4-6 months), starting in childhood.

  • Prevention: Lifelong, strict sun protection and absolute avoidance of ionizing radiation.

  • Treatment:

    • BCCs: Surgical excision, Mohs surgery, or topical therapies (imiquimod, 5-FU). For numerous or advanced BCCs, Hedgehog pathway inhibitors (vismodegib, sonidegib) are used.

    • OKCs: Surgical enucleation with meticulous curettage or resection; close follow-up for recurrence.