Genetics of Cavernoma

Cavernoma can occur either sporadically or as a hereditary condition.

 

Approximately 20% of people with cavernomas have the hereditary form, meaning they have a genetic predisposition to developing the condition.

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The hereditary form of cavernoma is caused by a single gene mutation (a mistake in a gene). This mutation occurs in one of three genes:

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• CCM1

• CCM2

• CCM3

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People who carry a mutation in any of these genes will typically develop multiple cavernomas over their lifetime. The hereditary form of cavernoma is officially recognised as a rare disease.

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Inheritance and Family Risk

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Hereditary cavernoma follows an autosomal dominant inheritance pattern. This means that:

• A person who carries one of the CCM gene mutations has a 50% chance of passing the mutation on to each of their children.

• Both males and females can be affected.

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Genetic Testing

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Genetic testing can be carried out to look for mutations in the CCM1, CCM2, or CCM3 genes. Testing is usually offered when:

• A person has two or more cavernomas, or

• There is a family history of cavernomas.

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The results of genetic testing can help confirm whether a person has the hereditary form of cavernoma.

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Accessing Genetic Services in Ireland

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In Ireland, genetic clinics are based in the children’s hospitals. To attend a genetics clinic:

1. A referral from your GP is required.

2. The clinical genetics team will review your medical and family history.

3. They will then decide whether genetic testing is appropriate.

 

More information is available through Children’s Health Ireland – Clinical Genetics Services.

https://www.childrenshealthireland.ie/list-of-services/clinical-genetics/

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The CCM3 Gene (Ultra-Rare and More Aggressive)

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The CCM3 gene is the rarest of the three cavernoma genes and is considered the most aggressive form of hereditary cavernoma.

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• It is estimated that around 50 people in Europe have CCM3.

• People with CCM3 tend to develop a larger number of cavernomas than those with CCM1 or CCM2.

• They are also at a higher risk of brain haemorrhages.

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In approximately 50% of cases, CCM3 is associated with additional conditions, including:

• Scoliosis

• Cognitive disabilities

• Benign brain tumours, such as meningiomas

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Because of its rarity and complexity, CCM3 is often described as an “ultra-rare” gene.

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For further detailed information about CCM3, visit the Alliance to Cure Cavernous Malformation website.

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Frequently Asked Questions (FAQs)

 

Is cavernoma always genetic?

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No. Most cavernomas are sporadic, meaning they occur without a known genetic cause. About 20% are hereditary.

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If I have the gene, will I definitely develop cavernomas?

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Yes. People who carry a CCM gene mutation will develop multiple cavernomas over time, although symptoms and severity can vary widely.

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Can cavernoma skip a generation?

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A person must carry the gene to pass it on. However, some people may have few or no symptoms, which can make it seem like the condition has skipped a generation.

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Should my children be tested?

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Genetic testing for children is a complex decision and is usually discussed with a clinical genetics team, particularly if there is a confirmed familial mutation.

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What does a 50% chance of inheritance mean?

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Each child has an independent 1 in 2 chance of inheriting the gene mutation. This does not change based on how many children are affected or unaffected.

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Is CCM3 more serious than CCM1 or CCM2?

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CCM3 is generally considered more aggressive, with earlier onset, more cavernomas, and a higher risk of complications compared to CCM1 and CCM2.

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Can genetic testing change treatment?

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While it may not change immediate treatment, genetic testing can:

 

• Confirm a hereditary diagnosis

• Guide monitoring and screening

• Help inform family members of potential risk