Gorlin syndrome, also known as Gorlin-Goltz syndrome, basal cell nevus syndrome or nevoid basal cell carcinomacancer arising from tissues that line organs syndrome, is a rare genetic condition that is characterised by skeletal abnormalities, cystsabnormal growths that are usually filled with liquid or air on the jaw and a predisposition to malignancy, most notably basal cell carcinoma (BCC).
Familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
Gorlin syndrome is generally diagnosed equally among the sexes, and is often diagnosed before the age of 30. However, anyone can develop this disease.
Gorlin Syndrome Related Tumours
Gorlin syndrome is most commonly associated with the development of basal cell carcinomas, however it has also been linked to other types of tumours. Some examples include:
- Basal cell carcinoma.
- Medulloblastoma.
- Rhabdomyosarcoma.
- Benignnot cancerous, can grow but will not spread to other body parts tumours, most notably:
- Ovarian fibroma.
- Cardiac fibroma.
- Odontogenic keratocysts.
- Epidermoid cysts.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cellsthe basic structural and functional unit of all living things look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with Gorlin syndrome will present with a unique disease behaviour, with varying tumoura tissue mass that forms from groups of unhealthy cells locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignantcancerous, may grow and spread to other areas of the body (cancerous) or benign (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with Gorlin syndrome may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Photodynamic therapya procedure that involves inserting a light-sensitive drug (photosensitiser) to shrink and damage cancer cells when exposed to a light source.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Patients with Gorlin syndrome may be hypersensitive to radiation and radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells may increase the risk of developing other skin cancers. As such, doctors may not recommend this treatment.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Gorlin syndrome has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. Some recommendations for Gorlin syndrome may include:
- Annual physical examinations.
- Brain MRI every six months for children under age three, then annually until age eight.
- Cardiac ultrasounds in children.
- Annual x-raya type of medical imaging that uses x-ray beams to create detailed images of the body of the jaw.
- Abdominal and pelvic ultrasounds in females starting at puberty.
- Skin examinations every 2-3 months for adults.
Screening options for Gorlin syndrome may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
Gorlin syndrome is caused by a genetic mutation in one of the following genes:
- PTCH1a type of tumour supressor gene involved in the formation of tissues and organs, cell growth and cell division during embryonic development.
- PTCH2.
- SUFU.
PTCH1 and PTCH2 are tumour suppressor genes, which act to inhibit cell growth to prevent overproduction of cells and the development of tumours. The SUFU is a negative regulator of the Hedgehog signalling pathway, which is essential for healthy embryonic/fetal development.
Gorlin syndrome is an autosomal dominant disease, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.
Symptoms
The symptoms of Gorlin syndrome often vary by the type(s) of tumours present. General symptoms of Gorlin syndrome may include:
- Development of two or more BCCs before the age of 20.
- Cysts in the jaw.
- Pits in the palms of the hand and soles of feet.
- Macrocephaly.
- Enlarged jaw.
- Abnormally wide base of the nose.
- Unusually prominent forehead.
- Having extra fingers and/or toes.
- Fused fingers and/or toes.
- Funnel chest.
- Pigeon chest.
- Ocular abnormalities, such as:
- Scarring of one or both corneas.
- Cataracts.
- Glaucoma.
- Eyes that do not align with each other.
- Retinal pigmentation.
- Blindness.
- Calcification of falx cerebri (a part of the brain).
- Gynaecomastia.
- Hypogonadism in males.
- Bicornuate (heart-shaped) uterus.
- Cleft lip and/or palate.
- High arched palate.
- Intellectual impairment.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with Gorlin syndrome, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- X-ray.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Biopsyremoval of a section of tissue to analyse for cancer cells.