Nevoid basal cell carcinoma syndrome/Gorlin syndrome
Nevoid basal cell carcinoma syndrome / Gorlin syndrome (NBCCS/GS) (OMIM#109400, ORPHA:377) is a tumour predisposition syndrome mainly characterized by the development of multiple odontogenic keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas, usually from the third decade. Medulloblastoma, typically desmoplastic, can be diagnosed in early childhood. Cardiac and more frequently ovarian fibromas can occur. Tumour risks differ depending on the causative gene. Phenotypic features such as macrocephaly, hypertelorism, calcification of falx cerebri, skeletal anomalies and palmar and/or plantar pitting can also be observed. The prevalence is estimated to be near to 1 in 31,000.
Most cases of NBCCS/GS are caused by germline heterozygous pathogenic variants in Sonic Hedgehog signalling pathway genes - PTCH1 and SUFU. PTCH2 variants have also been discussed to cause NBCCS/GS. Approximately 30% have no identifiable cause.
NBCCS/GS is inherited in an autosomal dominant manner, meaning that each child of an affected individual has a 50% chance to inherit the familial variant and is at risk of developing disease. The proportion of de novo pathogenic variants (parents not carriers of the same variant) is approximately 20%-30% and in these cases there is no previous family history. Preimplantation and prenatal genetic testing are possible if the causal familial variant has been identified (different legal/ethical perspectives could exist).
It is recommended that regular surveillance is performed by a multidisciplinary specialized team beginning at early ages. The treatment for multiple BCC includes surgery complemented by other local treatments such as photodynamic therapy or topical treatments. Oral vismodegib may reduce development of BCC. Jaw keratocysts are often recurrent and repeated surgeries might be needed. Ovarian fibromas are usually managed with conservative surgery. Radiotherapy could increase the risk of basal cell carcinomas in irradiated area.
More information regarding Nevoid basal cell carcinoma syndrome/Gorlin syndrome can be found on:
GeneReviews® - Nevoid basal cell carcinoma syndrome/Gorlin syndrome
Orphanet: Gorlin syndrome
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Endorsed by ERN GENTURIS* |
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A guideline for the clinical management of basal cell naevus syndrome (Gorlin–Goltz syndrome). |
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* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.
ERN GENTURIS webinars - Thematic group 4: Other rare genturis
ERN GENTURIS webinars - General
A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.