Summary about Disease
Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare genetic disorder characterized by a variety of abnormalities, most notably the development of multiple basal cell carcinomas (BCCs), often starting in adolescence or early adulthood. Individuals with NBCCS are also prone to other tumors, including medulloblastomas (a type of brain tumor), odontogenic keratocysts (cysts in the jaw), and ovarian fibromas. Other common features include skeletal abnormalities, such as bifid ribs and fused vertebrae, and neurological problems.
Symptoms
Symptoms of NBCCS can vary widely but typically include:
Multiple basal cell carcinomas (BCCs), appearing as pink or pearly bumps on the skin.
Odontogenic keratocysts in the jaw.
Palmar or plantar pits (small depressions on the palms of the hands or soles of the feet).
Skeletal abnormalities (bifid ribs, fused vertebrae, scoliosis).
Macrocephaly (abnormally large head).
Medulloblastoma (brain tumor, more common in childhood).
Ovarian fibromas in females.
Calcification of the falx cerebri (a membrane in the brain).
Facial features like a prominent forehead, broad nasal root, and widely spaced eyes (hypertelorism).
Causes
NBCCS is caused by mutations in genes involved in the Hedgehog signaling pathway, most commonly the PTCH1 gene. Less frequently, mutations in the SUFU or PTCH2 genes can also cause the syndrome. These genes play a critical role in cell growth and development. The condition is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is needed for the disorder to manifest. In some cases, NBCCS can occur as a result of a new (de novo) mutation with no family history.
Medicine Used
Treatment for NBCCS focuses on managing the individual symptoms and tumors that develop. There is no cure for the underlying genetic condition.
Basal cell carcinomas: Surgical excision, Mohs surgery, curettage and electrodesiccation, cryotherapy, topical medications (imiquimod, 5-fluorouracil), photodynamic therapy, and radiation therapy may be used. Vismodegib and sonidegib, Hedgehog pathway inhibitors, are approved for advanced BCCs not amenable to surgery or radiation.
Odontogenic keratocysts: Surgical removal is the primary treatment.
Medulloblastomas: Treatment typically involves surgery, radiation therapy, and chemotherapy.
Ovarian fibromas: Surgical removal may be necessary. Pain medication and other supportive therapies are used as needed.
Is Communicable
NBCCS is not communicable. It is a genetic disorder, meaning it is caused by a mutation in a person's genes and cannot be spread from person to person.
Precautions
Individuals with NBCCS should take the following precautions:
Sun protection: Rigorous sun protection is crucial to minimize the risk of developing new BCCs. This includes wearing protective clothing, using broad-spectrum sunscreen with a high SPF, and avoiding prolonged sun exposure, especially during peak hours.
Regular medical checkups: Regular monitoring by a dermatologist, neurologist, and other specialists is essential to detect and treat tumors and other complications early.
Genetic counseling: Genetic counseling is recommended for individuals with NBCCS and their families to understand the inheritance pattern and the risk of passing the condition on to their children.
Avoid radiation exposure: X-rays and other forms of radiation should be minimized due to the increased risk of developing BCCs.
How long does an outbreak last?
There is no "outbreak" associated with NBCCS. It is a chronic condition characterized by the continuous or intermittent development of tumors and other symptoms throughout a person's life. Individual basal cell carcinomas can be treated and removed, but new ones may develop over time. The odontogenic cysts will develop and grow larger and will require treatment. There will be times where they will get better and worse.
How is it diagnosed?
Diagnosis of NBCCS is typically based on clinical criteria (presence of certain characteristic features) and can be confirmed by genetic testing. Diagnostic criteria may include:
Two or more basal cell carcinomas (BCCs) before age 30 or one BCC in an individual under age 20
Odontogenic keratocysts of the jaw
Palmar or plantar pits (three or more)
Calcification of the falx cerebri
Bifid, fused, or splayed ribs
First-degree relative with NBCCS
Medulloblastoma (especially desmoplastic type) Genetic testing can identify mutations in the PTCH1, SUFU, or PTCH2 genes, confirming the diagnosis even in the absence of all clinical criteria.
Timeline of Symptoms
The timeline of symptoms can vary significantly among individuals with NBCCS:
Childhood: Macrocephaly, medulloblastoma (more common under age 5), skeletal abnormalities (bifid ribs, fused vertebrae).
Adolescence/Early Adulthood: Onset of basal cell carcinomas, odontogenic keratocysts.
Adulthood: Continued development of BCCs, ovarian fibromas in females, calcification of the falx cerebri. The severity and timing of these symptoms are highly variable.
Important Considerations
Increased Risk of Cancer: Individuals with NBCCS have a significantly increased risk of developing multiple basal cell carcinomas, even with sun protection. They also have an increased risk of other cancers, such as medulloblastoma.
Genetic Counseling: Genetic counseling is essential for individuals with NBCCS and their families to understand the inheritance pattern and recurrence risk.
Multidisciplinary Care: Management of NBCCS requires a multidisciplinary approach involving dermatologists, neurologists, surgeons, oncologists, and other specialists.
Prognosis: The prognosis for individuals with NBCCS depends on the severity of the condition and the development of complications, such as aggressive tumors. Early diagnosis and comprehensive management are crucial for improving outcomes.