Definition
Gorlin syndrome (OMIM #109400) is a rare cancer predisposition syndrome caused by mutations in the PTCH1 or SUFU gene, which, can among other things, lead to early-onset basal cell carcinoma (BCC) and medulloblastoma along with cysts in the jaw or skeletal anomalies.
Key Data
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| Synonyms | Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome (NBCCS), basal cell nevus syndrome (BCNS) |
| Genes | PTCH1 (patched-1) and SUFU (suppressor of fused) |
| Gene products | Protein patched homolog 1 (PTCH1) and suppressor of fused homolog (SUFU) |
| Function | Part of the sonic hedgehog (SHH) signaling pathway |
| Heredity | Autosomal dominant |
| Prevalence | 1:30.000-1:57.000 |
| Genotype-phenotype correlation | The risk of developing medulloblastoma is much higher in combination with an SUFU mutation than with a PTCH1 mutation. In contrast, the incidence of basal cell carcinomas is lower in SUFU mutation carriers than in PTCH1 mutation carriers. Odontogenic keratocysts have also predominantly been described in PTCH1 mutation carriers. |
| Penetrance | Nearly 100% (in relation to the syndrome as opposed to development of the neoplasia) |
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Diagnosis
The diagnosis is confirmed if the following criteria are satisfied:
Major Criteria
Minor Criteria
The following X-ray diagnostics are generally required to confirm the diagnosis:
Blood relatives of an individual with a confirmed PTCH1 or SUFU mutation should undergo genetic testing for the presence of a PTCH1 and/or SUFU mutation as soon as possible, specifically in light of the early occurrence of medulloblastoma.
In pediatric oncology, particularly in patients with SHH-activated medulloblastoma, it is important to rule out Gorlin syndrome – even if no other features of the syndrome are present.
Differential Diagnoses
| Macrocephaly | Sotos syndrome, Beckwith-Wiedemann syndrome, isolated hydrocephalus, isolated megalencephaly |
| Basal cell carcinoma | Brooke-Spiegler syndrome, Basex syndrome, Rombo syndrome |
| Medulloblastoma | 9q22.3 microdeletion syndrome |
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Clinical Presentation
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Clinical manifestations |
Earliest onset |
| Macrocephaly (head circumference > 97th percentile) | From birth |
Congenital malformations
|
From birth |
| Gross motor developmental delay | From birth |
| Facial abnormalities (prominent forehead, coarse facial features, milia) | From birth |
| Skeletal abnormalities (e.g. bifid ribs, wedge vertebrae) | From birth |
| Medulloblastoma | 1-2 years of age |
| Calcification of the cerebral flax | Usually from 20 years of age |
| Odontogenic keratocysts (usually mandibular) | From 10 years of age; (4 years), rarely after age 30 |
| Basal cell carcinomas (usually in the face, back, and neck) | From 20 years of age; (2 years) |
| Palmar-plantar keratosis | From 20 years of age |
| Other skin manifestations: chalazion, atheroma, dermoid cyst | |
Other tumors
|
Depending on the tumor:
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Therapeutic Considerations
The use of radiotherapy massively increases the risk of developing basal cell carcinomas and should therefore only be used if no alternative therapy is available. The irradiated areas of skin should then be as small as possible.
Furthermore, X-ray diagnostics should be used sparingly as well.
Patients with Gorlin syndrome should avoid direct sunlight as much as possible.
