Summary about Disease
Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare genetic disorder that affects many parts of the body and increases the risk of developing certain cancers, particularly basal cell carcinoma (BCC). It is characterized by a combination of skeletal abnormalities, distinctive facial features, and tumors, both cancerous and non-cancerous. Individuals with Gorlin syndrome also have an increased sensitivity to radiation.
Symptoms
Symptoms of Gorlin syndrome can vary widely among individuals but commonly include:
Basal Cell Carcinomas (BCCs): Multiple BCCs, often appearing at a young age, even in childhood or adolescence.
Odontogenic Keratocysts (OKCs): Cysts in the jaw that can be painful or cause swelling.
Skeletal Abnormalities: Rib anomalies (bifid, fused, or missing ribs), scoliosis, and frontal bossing (prominent forehead).
Calcification of the Falx Cerebri: Calcium deposits in the membrane that separates the two hemispheres of the brain.
Palmar or Plantar Pits: Small, painless pits on the palms of the hands or soles of the feet.
Facial Features: Macrocephaly (large head), coarse facial features, and hypertelorism (widely spaced eyes).
Medulloblastoma: A type of brain tumor that occurs more frequently in children with Gorlin syndrome.
Ovarian Fibromas: Noncancerous tumors of the ovaries.
Cardiac Fibromas: Noncancerous tumors of the heart.
Eye Abnormalities: Strabismus, cataracts, glaucoma.
Causes
Gorlin syndrome is caused by mutations in genes involved in the Hedgehog signaling pathway, primarily the PTCH1 gene located on chromosome 9q22.3. About 70-85% of cases are due to mutations in this gene. Mutations in the SUFU gene (located on chromosome 10q24.32) account for a smaller percentage (around 2-3%). Rarely, mutations in other genes like PTCH2 may also cause Gorlin syndrome. It is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is sufficient to cause the disorder. In most cases, an affected individual inherits the mutated gene from one affected parent. However, in approximately 20-30% of cases, the syndrome results from a new (de novo) mutation in the gene, occurring spontaneously in the affected individual.
Medicine Used
There is no single "medicine" that cures Gorlin syndrome. Treatment focuses on managing individual symptoms and complications.
Basal Cell Carcinomas (BCCs): Treatment options include surgical excision, curettage and electrodesiccation, cryotherapy, topical medications (such as imiquimod or fluorouracil), photodynamic therapy, radiation therapy, and, in some cases, Hedgehog pathway inhibitors (such as vismodegib or sonidegib).
Odontogenic Keratocysts (OKCs): Surgical removal of the cysts is the primary treatment.
Medulloblastoma: Treated with a combination of surgery, radiation therapy, and chemotherapy.
Ovarian Fibromas: Monitoring may be sufficient, or surgical removal may be necessary if they cause symptoms.
Pain management: Painkillers can be used for pain management. Hedgehog pathway inhibitors (vismodegib and sonidegib) are approved for treating advanced basal cell carcinomas and can be used in Gorlin syndrome patients who develop numerous or aggressive BCCs. However, these medications can have significant side effects, and resistance can develop.
Is Communicable
No, Gorlin syndrome is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.
Precautions
Individuals with Gorlin syndrome should take the following precautions:
Minimize sun exposure: Wear protective clothing, use sunscreen with a high SPF, and avoid tanning beds.
Regular skin exams: Conduct self-exams and undergo regular skin cancer screenings by a dermatologist.
Avoid radiation exposure: Discuss the risks and benefits of X-rays and other radiation-based imaging with their doctors. Minimize exposure when possible.
Regular dental checkups: Monitor for the development of odontogenic keratocysts.
Genetic counseling: Seek genetic counseling for family planning purposes.
Early detection: Watch for symptoms and consult your doctor as soon as possible.
Inform healthcare providers: Alert all healthcare providers about the diagnosis of Gorlin syndrome before any medical procedures, including dental work.
How long does an outbreak last?
Gorlin syndrome is not an "outbreak" type of illness. It is a chronic genetic condition. Symptoms can develop over a person's lifetime. The tumors and cysts associated with it may appear at different ages and require ongoing management.
How is it diagnosed?
Gorlin syndrome is usually diagnosed based on clinical criteria and genetic testing. Clinical Criteria: These are a set of major and minor criteria. A diagnosis is typically made if a person meets certain combinations of these criteria. Major Criteria:
More than two basal cell carcinomas (BCCs) or one BCC under age 30
Odontogenic keratocysts (OKCs) of the jaw
Palmar or plantar pits (three or more)
Calcification of the falx cerebri
Bifid, fused or splayed ribs
A first-degree relative with Gorlin syndrome Minor Criteria:
Macrocephaly
Congenital malformations (cleft lip or palate, frontal bossing, hypertelorism)
Skeletal abnormalities (e.g., Sprengel's deformity, syndactyly)
Ovarian fibroma (especially if bilateral) or medulloblastoma Genetic Testing: Molecular genetic testing can confirm the diagnosis by identifying a mutation in the PTCH1 or SUFU gene. This is particularly useful when clinical findings are ambiguous or in at-risk family members.
Timeline of Symptoms
The timeline of symptoms can vary greatly, but here is a general overview:
Childhood/Adolescence: Odontogenic keratocysts (OKCs) often develop, skeletal abnormalities may be apparent, and medulloblastoma can occur.
Adolescence/Early Adulthood: Basal cell carcinomas (BCCs) typically begin to appear.
Throughout Life: Calcification of the falx cerebri is usually present by adulthood, and palmar/plantar pits may be noticeable at any age. Ovarian fibromas are more common in women of reproductive age. The risk of developing BCCs continues throughout life.
Important Considerations
Genetic Counseling: Crucial for affected individuals and their families to understand the inheritance pattern and risks of passing the condition on to future generations.
Multidisciplinary Care: Management often requires a team of specialists, including dermatologists, oral surgeons, oncologists, neurologists, and geneticists.
Prophylactic Measures: Sun protection and avoidance of radiation are essential to minimize the risk of developing BCCs.
Early Detection of Cancers: Regular screening is important for early detection and treatment of tumors.
Patient Support Groups: Connecting with other individuals and families affected by Gorlin syndrome can provide emotional support and valuable information.
Surgical Interventions: Multiple surgeries might be required to remove tumours/cysts.
Radiation Therapy: Patients with Gorlin Syndrome are prone to having side effects due to radiation.
Pregnancy: Gorlin Syndrome can complicate pregnancy.