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

Background

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 symptoms and outcomes are 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 CCM patients with detailed phenotypic and imaging data for longitudinal studies.
  • To identify clinical and genetic, and environmental modifiers influencing CCM lesion burden, severity, and progression.
  • 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 CCM patients. The study is currently in its third 5-year cycle. During the first 5 year cycle, the CCM project was focused on recruiting CCM1 cases with the common Hispanic mutation (CHM). In the second 5-year cycle, we expanded recruitment to include not only CCM1-CHM cases, but also other CCM1 mutation carriers. For the third 5-year cycle, we are recruiting all familial CCM cases. We will continue collecting 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(s) or saliva sample, and a stool 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 genetically confirmed diagnosis of CCM, 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

You are not eligible to participate if:

  • You are incarcerated.
  • You are homeless.
  • You or a surrogate are unable to provide consent.

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 to the right to inquire about participation.