6201: Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformation




Individuals with Cerebral Cavernous Malformations (CCMs) have clusters of abnormally enlarged blood vessels in the brain and spinal cord. These abnormal clusters can cause problems such as neurological morbidity which can include bleeding in the brain, neurological events, death, seizures or disabilities. Familial or inherited forms of CCM are caused by mutations in CCM1/KRIT1, CCM2/MGC4067, or CCM3/PDCD10, the most common of which is CCM1. The familial form of CCM is frequently seen in Hispanic families of the Southwest due to a founder mutation in CCM1 coined the ‘Common Hispanic Mutation’ (CCM1-CHM). However, even among family members with the exact same disease-causing mutation, a wide range in clinical outcome is observed. The purpose of this study is to understand the natural history, morbidity, and mortality of people living with familial CCM. In this study, we will collect clinical, genetic, imaging, and environmental information for people with familial CCM1 to look for risk factors affecting CCM disease severity and progression.

The overall research aims are:

  • To establish a clinical registry and database of familial CCM1 patients with detailed phenotypic and imaging data for longitudinal studies.
  • To identify clinical and genetic modifiers influencing CCM lesion burden.
  • To quantify lesion growth over time and develop biomarkers of disease severity and progression.

About this Study

This study is one of three projects participating in the Brain Vascular Malformation Consortium (BVMC) funded by the Office of Rare Diseases Research, which is part of the National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS). The CCM project is a cross-sectional and longitudinal study of familial CCM1 patients. The study is currently in the second 5-year cycle. During the first 5 year cycle, the CCM project was focused on recruiting CCM1 cases with the common Hispanic mutation (CHM). For the second 5-year cycle, we are expanding recruitment to include not only CCM1-CHM cases, but also other CCM1 mutation carriers. We will collect clinical, genetic, imaging, treatment, and outcome data in participants, and follow the cohort over time to understand the natural history of this disease.

For new study participants, you will be asked to:

  • Give permission for study staff to access your medical records to collect clinical information and to obtain copies of MRI scans and reports
  • Fill out a questionnaire about your quality of life, family history, and medical/surgical history
  • Give a blood sample and/or saliva sample
  • Give permission to store and use your CCM resected tissue for research (if undergoing surgery)
  • Participate in annual follow-ups to update medical, surgical, and neurological information

Targeted Enrollment

To be eligible to participate, you must:

  • Have a confirmed diagnosis of CCM1 by DNA testing, or
  • Meet 2 of the 3 following criteria:
    • Clinical diagnosis of CCM
    • Evidence of multiple cavernous malformations on MRI
    • Someone in your immediate or extended family has a clinical diagnosis of CCM1
  • Sign the consent form.

You are not eligible to participate if:

  • You are incarcerated.
  • You are homeless.

How to participate:

In order to participate, please contact the study coordinator or principal investigator of any of the participating institutions by phone or by email. Please use the information below to inquire about participation:


Barrow Neurological Institute, Phoenix
Shiza Shahid, Study Coordinator
Michael Lawton, MD, Principal Investigator


University of California, San Francisco
Avery Lui, Clinical Research Coordinator
Helen Kim, MPH, PhD, Principal Investigator

New Mexico

University of New Mexico
Myranda Robinson, Study Coordinator
Atif Zafar, MD, Principal Investigator

Angioma Alliance
Amy L. Akers, PhD, Principal Investigator