Gorlin SyndromeMarkus2020-10-13T14:34:09+02:00
What is Gorlin syndrome?
Gorlin syndrome (also called Gorlin-Goltz syndrome or basal cell nevus syndrome) is a genetic, or hereditary disease that can lead to malignant tumors in the skin (basal cell carcinoma) or the brain (medulloblastoma) in early childhood already, which is why Gorlin syndrome is one of the cancer predisposition diseases. Moreover, it can lead to cysts in the jaw or skeletal malformations (mainly of the ribs or spine), among other things.
How is Gorlin syndrome diagnosed?
What is the risk of cancer?
What causes Gorlin syndrome?
Is there a treatment?
Surveillance recommendations
What do I need to pay special attention to?
Support groups and additional information
For the diagnosis, the symptoms that occur with Gorlin syndrome were first divided up into major and minor criteria. It was then determined that the diagnosis of "Gorlin syndrome" can be confirmed by the presence of the following presentations:
2 major criteria and 1 minor criterion or 1 major criterion and 3 minor criteria
Genetic evidence of a mutation (change in the hereditary material) in the genes responsible for the development of Gorlin syndrome (PTCH1 or SUFU)
Major Criteria
Multiple basal cell carcinomas (> 5) or one basal cell carcinoma prior to the age of 30
First-degree relative with Basal cell carcinoma
Calcification of the cerebral falx (part of the hard cerebral membrane that separates the two halves of the cerebrum) prior to the age of 20
Cysts in the jaw
Keratinization disorders in the hands and/or feet (> 1)
Minor Criteria
Childhood medulloblastoma
Cysts in the abdomen or lungs
Macrocephaly (above-average skull size)
Cleft lip/palate
Vertebral/rib anomalies
Polydactyly (extra fingers or toes)
Fibromas (benign tumors) of the ovaries or heart
Eye anomalies (cataract), developmental defects, pigment changes in the retina)
Multiple X-ray examinations are generally needed to confirm the clinical diagnosis, including X-ray examinations of the skull, jaw, lungs, and spine.
Since a hereditary disease is involved, blood relatives of a person with a proven genetic alteration, predominantly due to the early onset of medulloblastomas, should be genetically tested as soon as possible.
In children belonging to specific medulloblastoma subgroups ("SHH group"), it is always important to rule out Gorlin syndrome, even if other features of the syndrome are missing.
Other Clinical Features
There is a wide variety of clinical symptoms, which develop in an age-related manner. The following list includes not only primary features, such as basal cell carcinoma, medulloblastoma, cysts in the jaw, etc. (see major and minor criteria), but also other findings:
Gross motor developmental delay
Facial anomalies: Large forehead, coarse facial features, milia (bump-like cysts under the skin)
Other skin manifestations: chalazion, atheroma, dermoid cyst (a benign tumor that may include skin, hair, teeth, etc.)
Basal cell carcinomas may develop in early childhood already; however, they generally do not develop until late adolescence or early adulthood. 10% of patients with Gorlin syndrome never develop a basal cell carcinoma. Patients with a light skin or who are frequently exposed to UV light (such as sunlight) have an increased risk. Following radiation therapy, such as for treating a medulloblastoma, the risk that basal cell carcinomas will develop in the area of skin exposed to the radiation is increased as well.
Medulloblastomas are malignant tumors of the cerebellum that usually manifest as part of Gorlin syndrome at the age of 1-2 years already. All in all, a medulloblastoma develops in around 5% of all patients with Gorlin syndrome. At this point, it is important to remember that Gorlin syndrome is caused by a change in two different genes. If the PTCH1 gene is affected, the risk of developing medulloblastomas is less than 2%. If there is a genetic change in the SUFU gene, however, there is a greatly increased risk of developing medulloblastomas, which is reported to be around 33%.
Gorlin syndrome is a genetic, or hereditary, disease that is caused by changes in two different genes. These genes are called PTCH1 and SUFU, and they encode two corresponding proteins. They are part of a signaling pathway that enables cells to respond to external signals. Now if there is an alteration in one of these genes, this also changes the corresponding protein, and the signaling pathway will no longer function correctly. This malfunction leads to the development of malformations or tumors.
For this reason, part of the diagnostics involves searching for mutations, or changes in the hereditary material, in one of the genes. This greatly depends on which of the two genes is affected: Changes in PTCH1 more often lead to basal cell carcinomas and cysts in the jaw, while mutations in SUFU result in the development of medulloblastomas much more frequently.
Gorlin syndrome occurs in approx. one in 30,000-57,000 people and is passed on by parents to their children in 70-80% of cases. Heredity is autosomal dominant in these cases, with a penetrance of nearly 100%, meaning that nearly every person who has the gene defect ends up suffering from Gorlin syndrome. However, not every patient develops a malignant tumor. The remaining 20-30% of cases are due to a spontaneous or new mutation, called a de novo mutation.
Treatment depends on which disease is present and the resulting symptoms.
Basal cell carcinomas should be treated as soon as possible, with the most important step being surgery, during which an attempt is made to remove the tumor as completely as possible. Surgical treatment may be supplemented with cold, laser, or photodynamic therapy. In severe cases, vismodegib therapy may be used.
Treatment of patients with a medulloblastoma consists of a combination of surgery and chemotherapy. Radiation should be avoided if at all possible, since the risk of subsequently developing basal cell carcinomas in the irradiated area increases drastically.
Cysts in the jaw can be surgically removed.
Fibromas of the ovaries can also be surgically removed, whereby it is usually possible to preserve the ovaries. For fibromas of the heart, regular heart examinations are generally sufficient.
Surveillance Recommendations for the Early Detection of Cancer
Surveillance recommendations essentially involve identifying the gene mutation. In other words, the goal is to determine whether the genetic change affects the PTCH1 or the SUFU gene.
Carriers of a PTCH1 Mutation
Annual dermatological examination starting at 10 years of age and every 2-3 months as of the first BCC
Baseline echocardiogram in infancy, if no abnormality detected no further regular echocardiography necessary
Dental examination with an X-ray of the jaw every 12-18 months, starting at age 8
Ultrasound of the ovaries starting at age 18
Due to the low risk of medulloblastomas: no radiological screening except if there are neurological anomalies or an increase in head circumference
Carriers of an SUFU Mutation
The same as with carriers of a PTCH1 mutation, but without performing an X-ray of the jaw
Additional medulloblastoma screening: MRI of the brain every 4 months until the age of 3 and then every 6 months until the age of 5
Self-Care and Support
What should I pay special attention to?
Direct sunlight should be avoided as much as possible to keep the risk of developing basal cell carcinomas from increasing.
Neurological anomalies may be symptoms of a medulloblastoma, ranging from headaches and sleepiness to loss of consciousness, vomiting in the morning, movement or coordination disorders, and a tendency to fall. You should seek a doctor right away if you observe one or more of these symptoms in your child.
Link to the "Gorlin Syndrome Group" website
Link to the "Basal Cell Carcinoma Nevus Syndrome Life Support Network" website