From the Guidelines
Yes, there are several genetic conditions associated with widespread diffuse numerous basal cell carcinomas, most notably Gorlin syndrome, which is caused by mutations in the PTCH1 gene, as reported in the most recent study 1.
Genetic Conditions Associated with Basal Cell Carcinomas
The genetic conditions associated with multiple basal cell carcinomas include:
- Gorlin syndrome (nevoid basal cell carcinoma syndrome or basal cell nevus syndrome) caused by mutations in the PTCH1 gene
- Bazex-Dupré-Christol syndrome linked to mutations affecting the ACTRT1 gene
- Rombo syndrome
- Xeroderma pigmentosum caused by defects in DNA repair genes These conditions involve different genetic pathways but share the common feature of predisposing affected individuals to develop numerous basal cell carcinomas.
Underlying Mechanism
The underlying mechanism typically involves dysregulation of the Hedgehog signaling pathway or impaired DNA repair mechanisms, which normally protect skin cells from UV radiation damage, as discussed in 1.
Management
Management of these conditions requires:
- Regular dermatologic surveillance
- Sun protection
- Often systemic medications like vismodegib or sonidegib that target the Hedgehog pathway to reduce tumor burden As noted in 1, referral should be considered for any individual with a personal history of or first-degree relative with any two criteria from the major or minor diagnostic criteria lists for nevoid basal cell carcinoma syndrome.
Key Considerations
It is essential to consider the genetic predisposition to basal cell carcinomas, especially in individuals with a family history of the disease or those who have been diagnosed with a genetic syndrome associated with an increased risk of basal cell carcinomas, as highlighted in 1.
From the FDA Drug Label
Patients with laBCC were required to have lesions for which radiotherapy was contraindicated or inappropriate (e.g., Gorlin syndrome or limitations because of location of tumor), Three of these patients had a diagnosis of Gorlin Syndrome Twelve of these patients had a diagnosis of Gorlin Syndrome Patients with laBCC were required to have lesions that had recurred after radiotherapy, unless radiotherapy was contraindicated or inappropriate (e. g. Gorlin syndrome; limitations because of location of tumor or cumulative prior radiotherapy dose)
Genetic conditions associated with widespread diffuse numerous basal cell carcinomas:
- Gorlin syndrome is a genetic condition associated with an increased risk of developing basal cell carcinomas, including widespread diffuse numerous basal cell carcinomas 2, 2, 3.
Key points:
- Gorlin syndrome is a genetic disorder that increases the risk of basal cell carcinomas.
- Patients with Gorlin syndrome may have lesions that are unresectable or require substantial deformity, making them candidates for alternative treatments.
- The presence of Gorlin syndrome is a factor in the diagnosis and treatment of basal cell carcinomas.
From the Research
Genetic Conditions Associated with Basal Cell Carcinomas
- Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a genetic condition associated with widespread diffuse numerous basal cell carcinomas 4.
- This syndrome is characterized by the development of multiple basal cell carcinomas, as well as other tumors such as ovarian fibromas and medulloblastomas 5.
- The genetic basis of NBCCS is linked to a tumor suppressor gene on chromosome 9q, which is important in the development of basal cell carcinomas, ovarian fibromas, and medulloblastomas 5.
- Patients with NBCCS typically present with a large number of basal cell carcinomas, which can be challenging to manage due to their frequency and potential for recurrence 4.
Pathogenesis and Treatment
- The pathogenesis of basal cell carcinomas is complex and involves the interaction between environmental and genetic factors, including the aberrant activation of the Hedgehog signaling pathway 6, 7, 8.
- Treatment options for basal cell carcinomas include surgical intervention, as well as minimally invasive treatments such as hedgehog pathway inhibitors, which have shown promise in managing advanced or metastatic disease 4, 6, 7, 8.
- Novel imaging tools and therapeutic approaches are being developed to improve the diagnosis and treatment of basal cell carcinomas, with a focus on achieving complete resolution and minimal side effects 7.