What is Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome)?
Gorlin syndrome, which may also be known as Gorlin-Goltz syndrome, basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a type of cancer that runs in families and is passed down from parents to their children. This condition is signified by the presence of numerous skin cancers known as basal cell carcinomas, and it can also cause abnormalities in the skeletal system (bones), eyes and nervous system. People with this syndrome often start developing multiple tumors from childhood.
What Causes Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome)?
Basal cell nevus syndrome is a condition caused by changes, known as mutations, in a specific gene called PTCH. This gene is responsible for creating a kind of antenna or receiver (transmembrane receptor) that detects signals from proteins named sonic hedgehog. When it comes to this syndrome, almost every person who inherits the mutated gene will develop some signs or symptoms of the condition but the intensity of these signs or symptoms can vary greatly among different people.
About 20% to 30% of cases of this syndrome aren’t inherited from the parents, but occur due to a new mutation in the individual’s own genes, known as de novo mutations. These cases usually occur randomly with no clear cause.
Risk Factors and Frequency for Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome)
Gorlin syndrome is a rare condition, estimated to affect about 1 in every 40,000 to 60,000 people. It affects men and women nearly equally. Although it can occur in any race, it is less common in African American and Asian groups, who represent only 5% of the cases. These groups are often diagnosed with related symptoms, such as keratocysts in the areas around the teeth, rather than basal cell skin cancers, which are more common in other races.
Signs and Symptoms of Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome)
Gorlin syndrome is a condition that can be noticed as early as infancy. Patients with this syndrome often develop basal cell carcinomas (BCCs), a type of skin cancer, although the average age at which these BCCs start appearing is typically around 20 years. These BCCs might show up as clear bumps with visible blood vessels, or they might look like skin tags. Among the symptoms, unusual pits are found in the palms and soles of 75% to 90% of patients.
Additionally, around half of the cases also report milia, which are small white bumps, and epidermal inclusion cysts — sac-like pockets of skin that contain fluid or semi-solid material. In some instances, patients may come to medical attention due to jaw cysts that cause pain, swelling, and drainage. These generally occur around the average age of 13 and have occasionally been seen to turn malignant.
In roughly 5% of the cases, the patients might also develop a type of brain tumor known as medulloblastoma, usually around the average age of two years. This can lead to seizures, intellectual disability, and other neurological conditions. Other common signs, seen in about 60% to 75% of patients, involve skeletal abnormalities that are often present at birth. These can include a range of conditions from split or flared ribs, a pronounced forehead, cleft lip or palate, fused spinal bones, pectus excavatum (a sunken chest), fused fingers, and underdeveloped thumbs.
Possible eye abnormalities like widely spaced eyes, congenital blindness, cataracts, crossed eyes, and defects in the retina or iris might also be noted. Cardiac fibromas, benign heart tumors, which can cause dangerously slow heart rates during general anesthesia, can also occur in some cases.
- Basal Cell Carcinomas that look like clear bumps or skin tags
- Unique pits in the palms and soles
- Milia (small white bumps)
- Epidermal inclusion cysts
- Jaw cysts causing pain, swelling, and drainage
- Medulloblastoma leading to seizures and other neurological conditions
- Skeletal abnormalities
- Eye abnormalities
- Cardiac fibromas leading to slow heart rates
Testing for Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome)
To diagnose Basal Cell Nevus Syndrome (BCNS), which is a genetic condition that increases the risk of skin and other cancers, a specific set of criteria must be met.
Major criteria include having more than two Basal Cell Carcinomas (BCCs) or one BCC under the age of 20, certain types of cysts in the jaw, unique skin changes on the palms of the hands or soles of the feet, specific calcifications within the brain, anomalous ribs, or having a close family member with BCNS.
Minor criteria could be a certain type of brain tumor (medulloblastoma), a larger head circumference, certain birth defects of the face and body (including wide-set eyes and defects in the chest, digits, and spine), specific skeletal abnormalities, as well as certain heart and ovarian tumors.
Genetic testing for a specific gene alteration (in a gene called PTCH1) might be suggested in certain situations: if there’s a need to confirm the disease in patients that don’t clearly meet the clinical criteria, if there’s a need to predict the disease in family members of affected individuals who do not have symptoms, or prenatal testing if there is a known familial mutation in the family.
Treatment Options for Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome)
Gorlin syndrome is a complex medical condition that requires team effort from different medical specialties. It is important that patients are closely monitored by a skin specialist, as this condition can lead to the development of skin cancers, known as Basal Cell Carcinomas (BCCs), which on rare occasions can spread to other parts of the body. Kids should have their skin checked by a skin specialist every year until they get their first skin cancer, then the checks should be increased to twice a year. Adults, on the other hand, should have a full skin check every four months.
For children, there are several baseline tests that are recommended. Due to the increased risk of brain cancer, it’s suggested that children have a yearly MRI scan of their brain until the age of 8. They should also have repeated X-rays of their jaw until they’ve had a cyst for the first time, then twice a year until there have been no cysts for two years or until they turn 21. A spine x-ray is also recommended at the age of one and repeated if they show symptoms or irregularities. Heart examinations are important to screen for heart tumors. Girls should have a pelvic ultrasound at menstrual onset or at 18 years to check for ovarian tumors. Regular examinations of speech, vision, and hearing as well as general development assessments are important for children with Gorlin syndrome.
Adults who weren’t diagnosed with Gorlin syndrome in their childhood should have a baseline brain MRI scan, genetic counseling, and possibly a psychological assessment if needed. Jaw x-rays should be taken as needed based on symptoms. If a patient has had a history of brain cancer, they should have a yearly neurological evaluation. Pregnant patients need careful monitoring because the condition increases the risk of water on the brain (hydrocephalus), small head size (microcephaly), and heart tumors in their babies.
Treating skin cancers in Gorlin syndrome can be difficult due to the sheer number of them. Various approaches have been used, including simple scraping and burning, freezing (cryosurgery), surgical removal, a precision surgical technique known as Mohs micrographic surgery, and a combination of the latter with laser treatment. Cream treatments, such as 5% 5-fluorouracil, 5% imiquimod, or light therapy (photodynamic therapy) have also been used. Additionally, a drug called Vismodegib, which blocks a specific biological pathway involved in cell development, can be used to treat the skin cancers. However, it can have adverse effects, and it has been noted that the skin cancers may grow back after stopping this treatment.
What else can Gorlin Syndrome (Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome) be?
There are various skin conditions that may resemble each other. Below are some of these:
- Bazex syndrome
- Fibrous papule of the face
- Melanocytic nevi
- Milia
- Pseudohypoparathyroidism
- Rombo syndrome
- Seborrheic keratosis
- Unilateral nevoid BCC with comedones
Each of these conditions has its own unique features and treatments, so accurate identification is essential.
