Gorlin syndrome is a rare, autosomal dominant genodermatosis due to PTCH1 gene mutation characterised by multiple basal cell carcinomas, odontogenic keratocysts, and bifid ribs.
Description
Gorlin syndrome, also known as Gorlin-Goltz syndrome or nevoid basal cell carcinoma syndrome (NBCCS), is a genodermatosis that predisposes to the development of a variety of benign and malignant tumours, most commonly basal cell carcinomas. This syndrome is characterised by the presence of multiple odontogenic keratocysts, basal cell carcinomas, and skeletal abnormalities such as bifid ribs and vertebral anomalies.
Pathogenesis
The pathogenesis of Gorlin syndrome involves mutations in the PTCH1 gene, a tumour suppressor gene that normally inhibits the Hedgehog signaling pathway, which is crucial for cell growth and differentiation. Mutations in PTCH1 cause unrestricted activation of this pathway, leading to tumourigenesis.
Subtypes
There are no recognised subtypes of Gorlin syndrome.
Epidemiology, Risk Factors & Associations
- Gorlin syndrome is a rare disorder, with an estimated prevalence of 1 in 60,000.
- The condition affects both sexes equally and has no racial predilection.
- Patients with Gorlin syndrome are highly susceptible to ionising radiation, which can exacerbate the development of basal cell carcinomas.
Clinical Features
- Multiple basal cell carcinomas, usually from early adulthood.
- Multiple odontogenic keratocysts – benign cystic lesions typically in the mandible or maxilla.
- Palmar and plantar pitting.
- Skeletal abnormalities: bifid ribs, scoliosis, and other vertebral defects.
- Intracranial ectopic calcifications, particularly in the falx.
Complications
The most significant complication is the development of multiple basal cell carcinomas, which can be disfiguring and occasionally metastasise (0.1% of cases).
Pathological Features
Histopathology
- Macroscopic: Basal cell carcinomas are small, pink or flesh-coloured nodules, often with telangiectasia.
- Microscopic: Basal cell carcinomas demonstrate nests of basaloid cells in the dermis, often with palisading of peripheral cells.
Serology
No specific serological markers for Gorlin syndrome.
Biochemistry
No specific biochemical markers for Gorlin syndrome.
Radiological Features
General Features
- Multiple odontogenic keratocysts in the mandible or maxilla. Typically located in the posterior mandible.
- Bifid ribs and other skeletal anomalies.
- Intracranial ectopic calcifications.
OPG
- Typically seen as a lucent, expansile lesion with smooth, corticated borders
CT
- Non-contrast: Multiple lucent lesions (keratocysts) in the mandible or maxilla.
- Contrast-enhanced: No specific features.
MRI
- T1WI: Variable signal. May be high due to cholesterol and keratin contents.
- T2WI: Keratocysts can be heterogenously hyperintense.
- T1 C+: May demonstrate peripheral enhancement but no specific solid component.
- DWI/ADC: Restriction due to keratin
Grading and Staging
There is no specific grading or staging system for Gorlin syndrome itself. Individual basal cell carcinomas are graded and staged according to their specific systems.
Diagnosis
Diagnosis is made based on clinical criteria, involving the presence of two major criteria, or one major and two minor criteria. Genetic testing can also be performed to identify PTCH1 mutations.
Major Criteria
- Multiple Basal Cell Carcinomas: More than two occurring over a lifetime or one under the age of 30.
- Odontogenic Keratocysts of the Jaw: Diagnosed histologically, particularly when occurring in younger patients.
- Three or More Palmar or Plantar Pits: Small pits in the skin of the palms of the hands or soles of the feet.
- Bilamellar Calcification of the Falx Cerebri: Seen on skull imaging.
- Bifid, Fused, or Markedly Splayed Ribs: Rib anomalies detectable on radiological imaging.
- First-Degree Relative with Gorlin Syndrome: A parent, sibling, or child diagnosed with the syndrome.
Minor Criteria
- Macrocephaly: Disproportionately large head size, adjusted for height.
- Congenital Malformations: Such as cleft lip or palate, frontal bossing, or “coarse face”.
- Other Skeletal Abnormalities: Including Sprengel deformity, pectus deformity, or syndactyly.
- Radiologic Abnormalities: Including bridging of the sella turcica, vertebral anomalies, or flame-shaped lucencies of the hands or feet.
- Ovarian Fibroma: Generally, a benign tumor of the ovary.
- Medulloblastoma: A type of brain tumour, particularly desmoplastic medulloblastoma.
Differential Diagnosis
- Other causes of multiple basal cell carcinomas, such as xeroderma pigmentosum, need to be considered. However, these typically lack the systemic features of Gorlin syndrome.
- Multiple odontogenic keratocysts can be seen in other conditions such as Ehlers-Danlos syndrome, but these conditions lack the other cutaneous and skeletal features of Gorlin syndrome.
Management
Management of Gorlin syndrome includes regular skin checks to monitor for new basal cell carcinomas, regular dental examinations and imaging to detect new keratocysts, and genetic counselling for family members. Basal cell carcinomas can be treated with local resection or topical agents, while keratocysts may require surgical removal.
Memory Aid
- G – Genetic: Inherited condition caused by mutations in the PTCH1 gene.
- O – Odontogenic Keratocysts: Mandibular cysts that are characteristic of the syndrome.
- R – Rib Anomalies: Bifid, fused, or missing ribs are common.
- L – Lamellar Calcification of the Falx Cerebri: Calcification in the brain, detectable on imaging.
- I – Increased Risk of Basal Cell Carcinomas: Numerous basal cell carcinomas at a young age.
- N – Nevi: Multiple skin nevi are common.