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Conditions

Gorlin syndrome

Gorlin syndrome, also known as naevoid basal cell carcinoma syndrome, is a rare genetic condition characterised by the development of jaw cysts, basal cell carcinomas, palmar pits and plantar pits.

Overview

Gorlin syndrome is inherited in an autosomal dominant pattern and affects many areas of the body, increasing a patient’s chance of developing various cancerous and non-cancerous tumours. A distinctive facial appearance is often present, as well as basal cell carcinomas and jaw cysts.

Clinical features

  • Jaw cysts (odontogenic keratocysts), which may develop in those <10 years.
  • Multiple basal cell carcinomas of the skin, which may develop in those <20 years.
  • Palmar and plantar pits.
  • Distinct facial features, including macrocephaly, frontal and temporoparietal bossing, hypertelorism, mandibular prognathism and, in some, cleft lip and palate.
  • Skeletal anomalies: bifid ribs, kyphoscoliosis, early calcification of falx cerebri (diagnosed with AP radiograph), rib and vertebrae anomalies.
  • Brachydactyly, thumb anomalies or polydactyly.
  • Ovarian or cardiac fibromas.
  • Eye anomalies, including cataract, coloboma and microphthalmos.
  • Medulloblastoma (typically desmoplastic), which occurs in 33% of individuals with SUFU variants and under 2% of individuals with PTCH1 variants, with peak incidence at 12 to 24 months of age.

Genomics

Gorlin syndrome is caused by loss-of-function genetic variants (nonsense, frameshift, missense, splicing and deletions) in PTCH1 (9q22.3) or, less commonly, SUFU (10q24.3).

Both genes have a tumour suppressor function, with basal cell carcinomas and medulloblastoma arising as a result of a ‘second hit’ inactivating the other copy of the PTCH1 or SUFU gene.

For information about testing in children, see Child with a suspected overgrowth-intellectual disability syndrome and Child with macrocephaly.

Diagnosis

A clinical diagnosis may be established in an individual presenting with two major or one major plus two minor features, as per recognised criteria (see the resources section below).

Major criteria

  • Lamellar (sheet-like) calcification of the falx, or clear evidence of calcification in an individual <20 years.
  • Jaw keratocyst: odontogenic keratocyst histologically.
  • Palmar/plantar pits (two or more).
  • Sonic hedgehog (SHH) medulloblastoma, confirmed on tumour testing.
  • Multiple basal cell carcinomas (>5 under 50 years).

Minor criteria

  • Childhood medulloblastoma where the SHH pathway in the tumour has not been investigated (also known as primitive neuroectodermal tumour.)
  • Lympho-mesenteric or pleural cysts.
  • Macrocephaly (occipitofrontal circumference (OFC) >97th centile).
  • Cleft lip or palate.
  • Vertebral or rib anomalies observed on chest x-ray and/or spinal x-ray; bifid, splayed or extra ribs; bifid vertebrae.
  • Preaxial or postaxial polydactyly.
  • Ovarian or cardiac fibromas.
  • Ocular anomalies (cataract, developmental defects and pigmentary changes of the retinal epithelium).

A molecular diagnosis is made on the finding of a heterozygous pathogenic variant in either PTCH1 or SUFU, with analysis through R214: Nevoid basal cell carcinoma syndrome or Gorlin syndrome.

For information about testing, see Multiple basal cell carcinomas in early age and/or Child with a suspected overgrowth-intellectual disability syndrome.

Inheritance and genomic counselling

Gorlin syndrome is an autosomal dominant condition. This means that:

  • affected individuals have one working copy of the relevant gene, and one with a pathogenic variant; and
  • the chance of a child inheriting the gene with the variant from an affected parent is 1 in 2 (50%).

Incomplete penetrance can also occur (that is, not everyone who has the variant develops the disease).

Around 70%–80% of individuals with Gorlin syndrome will have an affected parent, though the expression (features shown in individuals with the variant) can vary significantly both within and between families.

Where parents do not carry the pathogenic variant identified in the affected child, the recurrence risk will be less than 1%. The risk remains slightly above that of the background population due to the small possibility of germline mosaicism.

The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy. It is appropriate to offer genomic counselling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

Management

Management of children with Gorlin syndrome is principally supportive and suggested approaches, including skin and dental surveillance as well as avoidance of environmental factors that increase the risk of cancers, have been published by several authors.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 14/05/2025
  • Next review due: 14/05/2027
  • Authors: Dr Maria Gogou
  • Reviewers: Dr Ellie Hay, Dr Emile Hendriks, Dr Terri McVeigh, Professor Neil Rajan