Genetics
What causes Gorlin syndrome?
Gorlin syndrome is a genetic condition which means that it is caused by an alteration (also known as a mutation) in a gene. Genes are the instructions which tell the body how to make all the proteins it needs to survive and grow. Genes are inherited from our parents. Most of our genes are inherited in pairs, with one copy of each gene from your mother and the other from your father.
The two genes linked to Gorlin syndrome are called PTCH1 and SUFU.
PTCH1 was the first to be identified.
The SUFU gene was linked with Gorlin syndrome more recently.
Both of these genes produce proteins which work together in a “pathway” which controls the growth and division of certain cells. If these genes are not functioning correctly, then abnormal cell growth can occur and this results in the development of various growths and tumours .
Do faults in SUFU and PTCH1 cause the same problems?
PTCH1 gene alterations tend to cause the very typical features of Gorlin syndrome such as the dental cysts, basal cell skin cancers, large head size, skeletal differences and other common features included in the diagnostic criteria. Medulloblastoma can occur in children, but this is not common.
People with a mutation in SUFU tend not to have the odontogenic keratocysts. They may not have an unusually large head size. Unfortunately, children with SUFU gene alterations seem to have a higher chance of developing a brain tumour called a medulloblastoma. The exact risk of developing this tumour is not clearly established. This is because the gene alterations have often been found in families in which a child has had a tumour, and it is quite likely that many people with gene alterations do not have a medulloblastoma but have not been counted in the studies. This means that our estimates of the risk of medulloblastoma are likely to be “biased” and higher than they should be. It is clear that the vast majority of people with Gorlin syndrome do not develop medulloblastoma.
Genetic Testing
How is genetic testing helpful?
Genes are made up of long strings of chemical units called “bases” whose names can be abbreviated at C, A, T and G. The sequence of these chemical units can be “read” in a genetic test to see if there is an alteration in the normal sequence of bases.
If there is an alteration, this can confirm a diagnosis of Gorlin syndrome. Not everyone who has physical features of Gorlin syndrome has a gene alteration, but this does not necessarily mean the person does not have Gorlin syndrome. Sometimes it is just not possible to find the gene alteration with existing technology.
How do I access genetic testing?
If you are suspected to have Gorlin syndrome, then you will be referred to a clinical geneticist. This is a doctor with expertise in genetic conditions who can decide whether to offer a genetic test to look at the PTCH1 and SUFU genes. Clinical geneticists work in hospitals and there are clinical genetics departments in major hospitals covering the whole of the UK. Your dermatologist, maxillofacial surgeon, paediatrician or GP will know where to refer you. Clinical geneticists work with genetic counsellors, who are healthcare professionals with a science or nursing background, trained to discuss genetic conditions and to offer genetic testing. You may see a clinical geneticist or a genetic counsellor.
How is Gorlin syndrome inherited?
If a person has Gorlin syndrome, they have an alteration in one copy of their PTCH1 or SUFU genes. This diagram shows that when they have a child, the child will inherit either the copy with the alteration, or the copy without the alteration. They will also receive a copy of the gene from the other parent. Assuming that the other parent does not have Gorlin syndrome as well, this means that each child has a 1 in 2 or 50% chance of inheriting the alteration and being affected with Gorlin syndrome.
What are the next steps for my family if I have a gene alteration?
If you have a gene alteration, then other family members will be offered a genetic test to see if they also have the same alteration found in you. This would start with your closest relatives, for example, parents, siblings and children, and then extend outwards to the wider family. Your geneticist or genetic counsellor can advise on the best approach within your family.
Is it possible to avoid passing on Gorlin syndrome to a child?
If you want to have a child and you have Gorlin syndrome, you can discuss this with your geneticist. There are a variety of options available to couples who want to try to avoid having a child with the condition. These include “pre-implantation genetic testing” in which embryos are created by IVF (in-vitro fertilisation) and then tested at a very early stage for the gene alteration before the unaffected embryos are placed into the womb. Also, couples can opt for testing of the baby during a pregnancy.
How common is Gorlin syndrome?
A recent clinical guideline quotes a figure of 1 in 31 000 to 1 in 256 000 people affected by Gorlin syndrome. It is not a common condition. There may be some mildly affected families who have not been identified.
References
A guideline for the clinical management of basal cell naevus syndrome (Gorlin–Goltz syndrome) B.J.A. Verkouteren et al. British Journal of Dermatology (2022) 186, 215–226
Reviewed and verified by Medical Advisers in conjunction with the Gorlin Syndrome Group, April 2024