"Gorlin Syndrome" – What Is It?
Gorlin syndrome (also known as Gorlin-Goltz syndrome or basal cell nevus syndrome) is a genetic, i.e., hereditary disease that can lead to malignant tumors of the skin (basal cell carcinoma) or brain (medulloblastoma) from an early age. Gorlin syndrome is, therefore, a cancer-predisposition disease. It can also lead to jaw cysts or skeletal malformations, especially of the ribs and spine.
How Is "Gorlin Syndrome" Diagnosed?
For the diagnosis, the features occurring in Gorlin syndrome were first divided into major and minor criteria. It was then determined that the diagnosis of “Gorlin syndrome” is confirmed if the following constellation is present:
- 2 major criteria and 1 minor criterion or 1 major criterion and 3 minor criteria
- Genetic evidence of a mutation (genetic change) in the genes responsible for the development of Gorlin syndrome (PTCH1 or SUFU)
Major Criteria
- Multiple basal cell carcinomas (> 5) or a basal cell carcinoma before the age of 30
- First-degree relative with basal cell carcinoma
- Calcification of the falx cerebri (part of the hard meninges that separates the two cerebral hemispheres) before the age of 20
- Jaw cysts
- Cornification disorders on hands and/or feet (> 1)
Minor Criteria
- Medulloblastoma of childhood
- Cysts in the abdomen or lungs
- Macrocephaly (larger than average skull)
- Cleft lip/palate
- Vertebral body/rib anomalies
- Polydactyly (extra fingers or toes)
- Fibromas (benign tumors) on the ovaries or heart
- Eye abnormalities (cataracts, developmental defects, pigmentary changes in the retina)
Several X-ray examinations are usually required to confirm the clinical diagnosis. These include X-ray examinations of the skull, jaw, lungs, and spine.
As this is a hereditary disease, blood-related family members of a person with a proven genetic change should be genetically tested as early as possible due to the early occurrence of medulloblastoma in particular.
In children with special medulloblastoma subgroups (so-called SHH group), Gorlin syndrome should always be ruled out, even if other features of the syndrome are absent.
Further Clinical Criteria
The clinical symptoms are varied, and their development is age-dependent. In addition to the main features such as basal cell carcinoma, medulloblastoma, jaw cysts, etc. (see major and minor criteria), other findings are listed below:
- Gross motor development delay
- Facial anomalies: Balcony forehead, coarse facial features, milia (skin gravel)
- Other skin manifestations: Chalazion (chalazion), atheroma (sebaceous cyst), dermoid cyst (benign tumor that can contain skin, hair, or teeth, among other things)
What Is the Risk of Cancer?
Basal cell carcinomas can occur in early childhood but usually only develop in late adolescence to early adulthood. 10% of patients with Gorlin syndrome never develop basal cell carcinoma. There is an increased risk in patients with fair skin and in patients who are frequently exposed to UV light (e.g., sunlight). After radiation therapy, e.g., due to a medulloblastoma, there is also an increased risk of developing basal cell carcinoma in the irradiated skin area.
Medulloblastomas are malignant tumors of the cerebellum that usually manifest themselves at the age of 1-2 years as part of Gorlin syndrome. Overall, a medulloblastoma occurs in around 5% of all patients with Gorlin syndrome. It is important to know that Gorlin syndrome is based on altering two different genes. If the PTCH1 gene is affected, the risk of developing medulloblastoma is less than 2%. However, if there is a genetic alteration in the SUFU gene, there is a significantly increased risk of medulloblastoma, which is reported to be around 33%.
What Is Known About the Development of "Gorlin Syndrome "?
Gorlin syndrome is a genetic, i.e., hereditary disease caused by changes in two genes. These genes are called PTCH1 and SUFU and code for two corresponding proteins. These proteins are part of a signaling pathway that enables cells to respond to external signals. If one of the genes changes, the corresponding protein and the signaling pathway no longer function correctly. This malfunction consequently leads to the development of malformations or tumors.
Therefore, part of the diagnosis consists of finding mutations, i.e., changes in the genetic material in one of the genes. Which of the two genes is involved plays a significant role here: Changes in PTCH1 lead more frequently to basal cell carcinomas and jaw cysts, while mutations in SUFU lead significantly more regularly to the development of medulloblastomas.
Gorlin syndrome occurs in around one in 30,000-57,000 people and is passed on from parents to their children in 70-80% of cases. The inheritance is autosomal dominant and penetrates almost 100%, meaning nearly every individual will develop Gorlin syndrome if the genetic defect is present. However, not every patient develops a malignant tumor disease. The remaining 20-30% of cases are due to a spontaneous or new mutation, known as a de novo mutation.
Is There Any Form of Treatment Available?
The therapy depends on the disease and its existing symptoms.
Basal cell carcinomas should be treated as early as possible. The focus is on surgery, in which the entire tumor should be removed if possible. Cold, laser, or photodynamic therapy can support surgical therapy. In severe cases, therapy with vismodegib can be used.
The treatment of patients with medulloblastoma consists of a combination of surgical therapy and chemotherapy. Radiation should be avoided if possible, as the risk of subsequent development of basal cell carcinoma in the irradiated area increases considerably.
Jaw cysts can be surgically removed.
Ovarian fibroids can also be surgically removed, although the ovaries can usually be preserved. In the case of heart fibromas, regular cardiological monitoring is usually sufficient.
Diagnosis of " Gorlin Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Gorlin Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
The procedure for early detection measures also depends on the gene mutation, i.e., a distinction must be made as to whether the genetic change is present in PTCH1 or SUFU.
Carrier of a PTCH1 Mutation
- Dermatological examination from the age of 10 annually, from the first BCC every 2-3 months
- Basic echocardiogram in infancy, if unremarkable no further regular echocardiograms necessary
- Dental examination with X-ray of the jaw every 12-18 months, starting at 8 years of age
- Ultrasound of the ovaries from the age of 18
- Due to the low risk of medulloblastoma: no radiological screening, except in the case of neurological abnormalities or an increase in head circumference
Carrier of a SUFU Mutation
- As in carriers of a PTCH1 mutation, but without an X-ray of the jaw
- Additional medulloblastoma screening: MRI of the head every 4 months until the age of 3 years, then every 6 months until the age of 5 years
Gorlin Syndrome- What You Can Do Yourself
You Should Pay Attention to This
Direct sunlight should be avoided as much as possible so as not to increase the risk of developing basal cell carcinoma.
Neurological abnormalities can be symptoms of a medulloblastoma. These include headaches, drowsiness or even loss of consciousness, vomiting in the morning, movement or coordination disorders, and a tendency to fall. If you observe one or more of these signs in your child, you should urgently consult a doctor.
Further Information
- Self-help group for people with Gorlin-Goltz syndrome
- Link to website of the “gorlin syndrome group”
- Link to website of the “Gorlin Syndrome Alliance”
Gorlin syndrome is also being researched in our accompanying project Liquid Biopsy, so we encourage patients to register for this in addition to the CPS registry.
Any further questions?
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