Founder Mutations

Key points

  • Familial CCM can be passed down through families.
  • A child of an affected parent has a 50% chance of inheriting the gene change.
  • Only half of people with the mutation develop symptoms.
  • Some families share founder mutations, meaning they inherited the same gene change from a distant ancestor.

Familial CCM is inherited in what doctors call an autosomal dominant pattern. This means:

  • Only one parent needs to carry the gene change (mutation) to pass it on.
  • Each child has a 50% chance of inheriting the mutation.

You can learn more about this on our page about the Genetics of Cavernous Malformation.

It is possible to have familial CCM even if no one else in your family has been diagnosed.

There are several reasons why this can happen:

  • You might be the first person in your family with the genetic change that causes CCM. This is more likely with the CCM3 (also called PDCD10) gene.
  • Some people never develop symptoms. Only 50% of people with familial CCM develop symptoms.
  • Symptoms can appear later in life. The first symptoms most often appear between ages 20 and 50, when people may have already had children.
  • In the past, diagnosis was more difficult. Before modern MRI scans and genetic testing, many people with familial CCM were never diagnosed.

Genes can change (mutate) in many different ways. Sometimes a genetic change begins in one person many generations ago and is passed down through many generations of a family. This is called a founder mutation.

Researchers have identified three founder mutations in the United States. We continue to learn more about these mutations with the help of members of the Alliance to Cure Cavernous Malformation.

CCM1 Common Hispanic MutationCCM2 Exon 2-10 DeletionCCM2 Ashkenazi Mutation

CCM1 Common Hispanic Mutation (CCM1 Q455X)

This mutation is the most common among descendants of early Spanish settlers in Mexico and New Mexico.

Researchers have traced many affected families back to common ancestors from the early 1600s. It is estimated that tens of thousands of people may share this mutation. Learn more here.

CCM2 Exon 2-10 Deletion

In this mutation, a large portion of the CCM2 gene is missing.

Researchers have traced some families with this mutation to:

  • ancestors in South Carolina in the early 1800s
  • another group with ancestors in Missouri in the early 1800s

These families are likely connected further back in history. Learn more here.

CCM2 Ashkenazi Mutation (c.30+5_30+6delinsTT)

This mutation has been identified among people of Ashkenazi Jewish heritage. It is uncertain how common this variant is among people of Ashkenazi descent. Researchers are continuing to study the genealogy of the families who share it. Learn more here.

Every gene change that causes familial CCM has its own history. CCM founder mutations are found in other populations worldwide. We encourage families who share these mutations to connect and explore their shared ancestry and medical history.

Updated 3.14.26

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