Gorlin syndrome

Naevoid basal cell carcinoma syndrome; NBCCS; basal cell naevus syndrome

Gorlin syndrome is an autosomal dominant cancer-predisposition syndrome caused by germline mutations in PTCH1 (≈85%) or SUFU (≈5%) — components of the hedgehog signalling pathway. Hallmarks are multiple BCCs, odontogenic keratocysts, palmar/plantar pits, and characteristic skeletal and craniofacial features.

CurrentLast reviewed 20 March 2026

Key points

Diagnosis is clinical (BCNS International Colloquium 2011 / Bree & Shah criteria) ± germline PTCH1 or SUFU confirmation. Suspicion from any of: BCC < 20 years, >5 BCCs lifetime, histologically proven jaw keratocyst, palmar / plantar pits, falx calcification, family history.

SUFU mutations carry a substantially higher medulloblastoma risk than PTCH1 — about one-third vs <2% in published genetically confirmed cohorts, though SUFU estimates may be inflated by ascertainment. This drives more intensive paediatric brain MRI surveillance in SUFU carriers (typically 4-monthly to age 3, then less frequent surveillance to age 5–8 depending on local protocol) than in PTCH1 carriers.

Avoid radiotherapy where possible — it can trigger numerous new BCCs in irradiated fields and should only be considered when no reasonable surgical or non-radiotherapy alternative exists.

Vismodegib is EMA-licensed for locally advanced or metastatic BCC and is effective in Gorlin syndrome to reduce tumour burden; significant side effects (alopecia, dysgeusia, muscle cramps, teratogenicity) limit long-term tolerance. NICE TA489 (2017) did not recommend routine NHS use — it is not a routine NHS-commissioned option, so any use in Gorlin syndrome needs specialist MDT and current NHS England / local funding or IFR confirmation.

Coordinated multidisciplinary care: dermatology, plastic surgery, oral & maxillofacial, paediatric neurology / oncology, genetics.

Diagnostic criteria (BCNS International Colloquium 2011 — Bree & Shah)

This page uses the BCNS International Colloquium 2011 framework (Bree & Shah, Am J Med Genet A 2011;155A:2091–7) throughout. Diagnosis requires 2 major criteria, OR 1 major + 2 minor criteria, OR genetic confirmation of a pathogenic PTCH1 or SUFU variant.

Major criteria

BCC < 20 years of age, or > 5 BCCs in a lifetime.
Odontogenic keratocyst of jaw (proven on histology).
≥ 3 palmar or plantar pits.
Bilamellar (lamellar) calcification of the falx cerebri.
Bifid, fused or markedly splayed ribs.
First-degree relative with Gorlin syndrome (BCNS).

Minor criteria

Macrocephaly (occipitofrontal circumference > 97th centile, with frontal bossing).
Congenital malformations (cleft lip / palate, polydactyly).
Other skeletal abnormalities (Sprengel deformity, marked pectus, short metacarpals).
Radiological abnormalities (bridging of sella turcica, vertebral anomalies).
Ovarian or cardiac fibroma.
Medulloblastoma (especially desmoplastic / nodular type, presenting under age 5).

Note: the UK NHS Genomic Medicine Service eligibility criteria (Evans / Farndon) used to gate single-gene PTCH1/SUFU testing in adults overlap with but are not identical to the BCNS 2011 criteria above; for any patient seen in clinical genetics, the local R-code referral criteria should be confirmed at the time of referral.

Management

Skin surveillance and BCC management

3-monthly initial review, then individualised by lesion frequency.
Surgical excision is first-line; Mohs micrographic surgery for high-risk sites.
Topical imiquimod / 5-FU for superficial multifocal disease.
Photodynamic therapy for thin lesions.
Vismodegib for high-burden disease unsuitable for further surgery — NICE TA489 did not recommend routine NHS use, so confirm any current NHS England / local funding or IFR route before use.
Avoid radiotherapy — accelerates new BCC formation.

Multisystem surveillance

Brain MRI — SUFU carriers (medulloblastoma risk about one-third in published cohorts): 4-monthly MRI to age 3, then less frequent surveillance to age 5–8 per the 2017 international Foulkes consensus, adapted to local paediatric neuro-oncology protocol. PTCH1 carriers (risk <2% in genetically confirmed series): less intensive surveillance is acceptable; many centres recommend MRI at presentation and then symptom-led / protocolised review. Confirm the local UK protocol with paediatric neuro-oncology.
Orthopantomogram (OPG) — annual from age 8 to detect odontogenic keratocysts.
Pelvic ultrasound — for women, baseline post-puberty, repeat for symptoms (ovarian fibroma).
Cardiac echo in childhood (cardiac fibroma).

Genetic counselling

Refer to clinical genetics for confirmation, family screening and pre-implantation genetic diagnosis discussion. 100% lifetime penetrance approached but variable severity within families.

ImportantPhotoprotection from infancy

Lifetime UV protection (broad-spectrum SPF 50+, clothing, hats, shade-seeking) is mandatory and should start in infancy. Sunbeds are absolutely contraindicated.

References

Bree AF, Shah MR. Consensus statement from the first international colloquium on basal cell nevus syndrome. Am J Med Genet A; 2011;155A:2091–7.

Foulkes WD et al. Recommendations for surveillance for predisposition to early onset brain tumors: Gorlin syndrome and rhabdoid tumor predisposition syndrome. Clin Cancer Res; 2017;23:e62–e67.

Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis; 2008;3:32.

NICE. Vismodegib for treating basal cell carcinoma (TA489). 2017 — not recommended for routine NHS use; check current NHS England / local specialist commissioning or IFR route before use.