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

< swipe to see entire table >
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)
< swipe to see entire table >


The diagnosis is confirmed if the following criteria are satisfied:

  • 2 major criteria and 1 minor criterion or 1 major criterion and 3 minor criteria

  • Evidence of a heterozygous germline mutation in the PTCH1 or SUFU gene
    Order of genetic testing recommended:

    1. PTCH1 sequence analysis
    2. PTCH1 deletion/duplication analysis
    3. SUFU sequence analysis
    4. SUFU deletion/duplication analysis
    5. PTCH1 RNA analysis

Major Criteria

  • Multiple basal cell carcinomas (> 5) or one basal cell carcinoma before the age of 30

  • First-degree relative with BCC

  • Lamellar calcification of the cerebral falx before the age of 20

  • Odontogenic keratocysts

  • Palmar/plantar keratosis (two or more)

Minor Criteria

  • Childhood medulloblastoma

  • Lymphoma-mesenteric or pleural cysts

  • Macrocephaly (head circumference > 97th percentile)

  • Cleft lip/palate

  • Vertebral/rib abnormalities

  • Pre- and postaxial polydactyly

  • Ovarian or cardiac fibroma

  • Ocular abnormality (cataract, developmental defects, retinal pigment changes)

The following X-ray diagnostics are generally required to confirm the diagnosis:

  • Cranial X-ray, AP and lateral

  • Orthopantomogram

  • Thoracic X-ray

  • Spinal X-ray

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
< Tabelle seitlich verschiebbar >

Clinical Presentation

< swipe to see entire table >

Clinical manifestations

Earliest onset

Macrocephaly (head circumference > 97th percentile) From birth
Congenital malformations

  • Cleft lip/palate
  • Polydactyly
  • Severe eye abnormalities (strabismus, cataract, orbital cyst, microphthalmus, retinal pigment changes)
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

  • Cardiac fibroma
  • Ovarian fibroma
Depending on the tumor:

  • From birth
  • Unclear, usually an incidental finding
< swipe to see entire table >

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.

Surveillance Recommendations

Surveillance Recommendations

PTCH1 Mutation Carriers

  • Annual dermatological examination starting at 10 years of age and every 2-3 months from the first BCC

  • Regular ECGs during infancy and early childhood

  • Dental examination with an X-ray of the jaw every 12-18 months, starting at age 8

  • Ovarian ultrasound from 18 years of age

  • Due to the low risk of medulloblastoma: no radiological screening unless there are neurological anomalies or if the head circumference increases

SUFU Mutation Carriers

  • The same as with carriers of a PTCH1 mutation, but without performing an X-ray of the jaw

  • Additional medulloblastoma screening: cranial MRI every 4 months until the age of 3 and then every 6 months until the age of 5

Additional Information

Open Clinical Trials / Registries

Support Groups