An uncommon familial cancer syndrome, NBCCS or Gorlin Syndrome is nevertheless important as it affects younger patients and radiotherapy is typically avoided. It has also provided insight into the carcinogenesis of basal cell carcinomas.
Gorlin syndrome is due to germline deactivating mutation in the PTCH1 (patched) gene. PTCH1 is involved in the Sonic Hedgehog (SHH) signally pathway; SHH binds to PTCH1, causing it to release SMO (Smoothened). This leads to unrestricted activity of SMO which promotes cell survival and malignant transformation.
PTCH1 has been indicated in the carcinogenesis of sporadic BCC as well as medulloblastoma.
Gorlin syndrome is associated with:
- Early onset of multiple BCCs (usually hundreds)
- Odontogenic bone cysts in the jaw
- Palmar 'pits' (1-2 mm red depressed lesions on the palms)
- Ectopic intracranial calcification
A minority develop 'early onset' medulloblastoma, usually of desmoplastic subtype (~ 5%).
The main problem with management is the hundreds of BCCs that develop. These should be treated early to prevent extensive surgical exision, with surgical excision, Mohs micrographic surgery in critical sites, or electrodessication/curetage. Radiotherapy should be avoided.
Medulloblastomas typically occur at a younger age (median 2); radiotherapy in this age group should be avoided anyway but if used will induce hundreds of BCCs. It is therefore important to use schedules that avoid RT where possible although this will lead to lower cure rates.
Interaction with Radiotherapy
Radiotherapy should be avoided unless there is no alternative; in combination with the loss of PTCH radiotherapy can induce hundreds of skin cancers.
D: Familial Cancer
- BRCA 1 & 2
- Cowden Syndrome
- Familial Adenomatous Polyposis (FAP)
- Familial Cutaneous Melanoma
- Li Fraumeni Syndrome
- Lynch Syndrome (Hereditary Non-Polyposis Colon Cancer)
- MEN 1 and MEN 2
- Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Peutz-Jeghers Syndrome
- Tuberous Sclerosis Complex (TSC)