PTCH1 germline pathogenic variants cause Nevoid Basal Cell Carcinoma Syndrome (NBCCS / Go...
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| ID | BMA-PTCH1-GERMLINE-NBCCS-GORLIN |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-BCC |
| Sources | SRC-NCCN-SKIN-2025 |
Faits relatifs à l ' action en justice
| Biomarqueur | BIO-PTCH1-GERMLINE |
|---|---|
| Variante | PTCH1 pathogène génomique (SNBC/syndrome de Gorlin) |
| Maladie | DIS-BCC |
| Niveau ESCAT | IIA |
| Combinaisons recommandées | vismodegib 150 mg PO daily — locally advanced / metastatic BCC; off-label BCC-burden reduction in NBCCS (intolerance of recurrent surgery), sonidegib 200 mg PO daily — locally advanced BCC; off-label NBCCS BCC-burden reduction, topical 5-fluorouracil / imiquimod — superficial BCC field therapy adjunct, dermatology q3-6mo with photodynamic therapy / curettage for low-risk lesions; Mohs for high-risk sites, oral/maxillofacial surgery follow-up for odontogenic keratocyst (recurrence-prone — marsupialization vs enucleation), minimize EBRT exposure (BCC induction in irradiation field is a known late effect) |
| Contre-indiqué en monothérapie | radiothérapie par faisceau externe pour le médulloblastome lorsque des solutions de remplacement sont disponibles — provoque des CBC sur le terrain (problème spécifique au NCCCS) |
| Résumé des faits | PTCH1 germline pathogenic variants cause Nevoid Basal Cell Carcinoma Syndrome (NBCCS / Gorlin syndrome) — characterized by multiple early-onset basal cell carcinomas (BCCs, often hundreds over a lifetime), odontogenic keratocysts of the jaw, palmar/plantar pits, macrocephaly, rib + skeletal anomalies, cardiac fibroma, and ~5% lifetime risk of desmoplastic-type medulloblastoma (SHH subgroup) — peak age 1-2 years. Confirmed-carrier surveillance protocol (per Bree & Shah 2011 / NCCN Skin): pediatric brain MRI q6mo from diagnosis through age 3 then annually through age 7 (medulloblastoma); whole-body dermatology q6mo from infancy for BCC detection (transition to q3mo after first BCC); jaw OPG / panoramic radiograph q1y from age 8 for odontogenic keratocyst; echocardiogram in infancy for cardiac fibroma; minimize ionizing radiation exposure (BCCs induced by EBRT — avoid radiotherapy for medulloblastoma when alternatives available). Vismodegib and sonidegib (Hedgehog-pathway smoothened inhibitors) are active for locally advanced/metastatic BCC and for BCC-burden reduction (off-label), sur... |
Notes
STUB — Wave A+B germline expansion. Linked Indication: none (no Gorlin/ NBCCS-specific Indication exists yet). Two-Clinical-Co-Lead signoff queued. PTCH1 carriers face the BCC-treatment paradox: surgical excision is gold standard but cumulative scarring + functional impairment make Hedgehog- pathway inhibitors attractive for diffuse disease — vismodegib drug-holiday protocols (3 mo on / 3 mo off) attempt to balance efficacy with muscle cramps, alopecia, dysgeusia, weight loss. SUFU germline (BMA-SUFU-GERMLINE- MEDULLOBLASTOMA) is the alternate NBCCS-like locus.
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No reverse references found in the YAML corpus.