Gorlin Syndrome
Also known as: Nevoid Basal Cell Carcinoma Syndrome (NBCCS), Basal Cell Nevus Syndrome (BCNS), Gorlin-Goltz Syndrome
Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare genetic disorder characterized by a combination of developmental abnormalities and a high predisposition to certain cancers, particularly basal cell carcinomas (BCCs). The syndrome is caused by mutations in genes involved in the hedgehog signaling pathway, which plays a critical role in cell growth and development. Individuals with Gorlin syndrome may develop multiple BCCs, often starting in adolescence or early adulthood, as well as other benign and malignant tumors. Other common features include distinctive facial features, skeletal abnormalities, and neurological issues.
Imagine having a superpower where you get lots of tiny bumps on your skin that need to be taken care of. Gorlin Syndrome is like that, but it also can cause other things like jaw cysts and sometimes problems with your bones. Doctors help by removing the bumps and treating any other issues that come up.
Signs & Symptoms
- Multiple basal cell carcinomas (BCCs)
- Odontogenic keratocysts (OKCs) of the jaw
- Skeletal abnormalities (e.g., bifid ribs, scoliosis)
- Calcification of the falx cerebri
- Palmar or plantar pits
- Macrocephaly
- Facial features (e.g., prominent forehead, coarse facial features)
- Medulloblastoma (in some cases)
- Ovarian fibromas (in females)
- Cardiac fibromas
- Intellectual disability (in some cases)
- Cleft lip or palate
Treatment Options
Surgical excision of basal cell carcinomas
HIGHLY EFFECTIVEMohs micrographic surgery for basal cell carcinomas
HIGHLY EFFECTIVERadiation therapy for basal cell carcinomas
MODERATELY EFFECTIVEVismodegib (Erivedge)
HIGHLY EFFECTIVE Approved 2012Sonidegib (Odomzo)
HIGHLY EFFECTIVE Approved 2015Cryotherapy for small basal cell carcinomas
MODERATELY EFFECTIVECurettage and electrodesiccation for small basal cell carcinomas
MODERATELY EFFECTIVEManagement of odontogenic keratocysts (OKCs)
HIGHLY EFFECTIVESupportive care for skeletal and neurological abnormalities
SUPPORTIVEDiagnosis
- Clinical examination
- Radiographic imaging (e.g., X-rays, CT scans, MRI)
- Genetic testing (mutation analysis of PTCH1, SUFU, or other related genes)
- Histopathological examination of skin lesions or cysts
History
Gorlin syndrome was first described in detail by Robert James Gorlin and Robert W. Goltz in 1960, who recognized the association between multiple basal cell carcinomas, odontogenic keratocysts, and skeletal abnormalities. The underlying genetic basis was later identified with the discovery of mutations in the PTCH1 gene in the mid-1990s, followed by the identification of mutations in SUFU and other genes involved in the hedgehog signaling pathway.
Recent Breakthroughs
FDA Approval of Vismodegib for Advanced Basal Cell Carcinoma
Vismodegib, a hedgehog pathway inhibitor, was approved by the FDA for the treatment of advanced basal cell carcinoma, including cases associated with Gorlin syndrome. This marked a significant advancement in the medical management of BCCs in these patients.
FDA Approval of Sonidegib for Advanced Basal Cell Carcinoma
Sonidegib, another hedgehog pathway inhibitor, received FDA approval for the treatment of advanced basal cell carcinoma. This provided an additional therapeutic option for patients with Gorlin syndrome who are not candidates for surgery or radiation.
Improved Understanding of SUFU-Related Medulloblastoma Risk
Research has refined the understanding of the increased risk of medulloblastoma in individuals with SUFU mutations, leading to improved surveillance protocols and earlier detection of these tumors.