Common Mutations

Familial Cavernous Malformation Mutations with a History

Familial cavernous malformation (CCM) is an illness that can sometimes be traced back in families for many generations.

This occurs because:

  • CCM genetic mutations are autosomal dominant mutations. This means that only one parent must have the mutated gene for there to be a chance of passing it down. Each child of an affected parent will have a 50% chance of inheriting the mutation. Please see Genetics of Cavernous Malformation for more information on the genetics of the illness.
  • Familial CCM may not affect those who have a mutation from having children.
    • We estimate that only 50% of those with familial CCM become symptomatic. This means, especially before MRI and genetic testing, half of those with the illness would never know they had it. It would not impede their ability to have a family.
    • Even for those who become symptomatic, the first symptoms are most likely to present between the ages of 20 and 40. These are people who may already have families.
    • Finally, those who develop symptoms may not have symptoms severe enough to prevent having families.
  • Some populations of people remain relatively isolated or are more likely to have very large families, both of which can lead to an increase in the number of people with the mutation over time.

A gene can mutate in hundreds or thousands of ways. We know that these families are related because, in addition to shared heritage, they share the exact same mutation of a gene. This is called a founder mutation.

In the United States, there are three known founder mutations. We continue to learn more about each with the help of Alliance to Cure Cavernous Malformation members. Please visit the individual webpage for each founder mutation to learn how you can help.

  • The Common Hispanic Mutation of the CCM1 gene is prevalent among descendants of the original Spanish settlers of Mexico and New Mexico. We have the most information about this mutation and can trace affected families back to common ancestors from the early 1600s. We believe there are tens of thousands of individuals who share this mutation.
  • The CCM2 Exon 2-10 Deletion is a mutation in which a large portion of the CCM2 gene as well as the next gene, NACAD, is missing. We are beginning to understand the genealogy of this mutation and have traced some families to shared ancestors in South Carolina in the early 1800s and another set of families to a shared ancestor in Missouri from the early 1800s. This mutation definitely goes back further and we expect these two families to be connected as we learn more.
  • The CCM2 Ashkenazi Mutation is found among those of Ashkenazi Jewish heritage. It is a specific mutation of the first exon of the CCM2 gene. We are just beginning to work on the genealogy of these families.

CCM founder mutations exist in other populations around the world. We encourage those who are part of these families to join together to explore their common ancestry.

Updated 4.17.22