301-519-2100 • FAX 301-519-2892 • 207 PERRY PARKWAY GAITHERSBURG, MD 20877  
 
  
SEARCH

Familial Cerebral Cavernous Malformations

  • KRIT1
  • CCM2
  • PDCD10
Cerebral cavernous malformations (CCM) are predominantly central nervous system vascular lesions formed by a cluster of grossly dilated blood vessels. Features and symptoms can include seizures, epilepsy, focal neurological deficits, chronic headaches, stroke, and cerebral hemorrhage. Individuals may be clinically asymptomatic; MRI may be necessary to diagnose asymptomatic lesions in at-risk individuals. CCM is inherited in an autosomal dominant manner with incomplete penetrance and disease-causing mutations have been identified in 3 genes: KRIT1, CCM2, and PDCD10. A mutation in one of these three genes is identified in 78% of individuals with a clinical diagnosis and family history of CCM; the detection rate is lower (45-67%) in isolated cases, in which individuals have multiple lesions. Individuals of Southwest-American Hispanic ancestry have a common mutation in KRIT1.

GeneDx offers bi-directional sequence analysis of the complete coding regions of the KRIT1, CCM2, and PDCD10 genes as well as deletion/duplication testing at the exon level by targeted array CGH (ExonArrayDx) for these genes. Analysis of KRIT1 is available in tiers. KRIT Tier 1 includes analysis of exons 14, 16, and 18 (previously published as exons 13, 15, and 17 using alternate nomenclature), where 56% of all mutations in KRIT1 have been identified; this includes the common Southwest-American Hispanic Q455X mutation in exon 14. KRIT Tier 2 analysis includes sequencing of the remaining exons of KRIT1 and concurrent ExonArrayDx analysis of the KRIT1, CCM2, and PDCD10 genes. If negative, sequencing of CCM2 and PDCD10 is available. As approximately 81% of individuals with familial CCM are expected to have a mutation that could be identified in Tier 1 or 2, reflex testing is the most cost-effective approach. For individuals who present with early onset in childhood, sequencing first the PDCD10 gene is indicated.

Once a disease-causing mutation is identified in an affected individual, mutation-specific testing of other at-risk family members and prenatal diagnosis are available.

Note, that buccal brushes can NOT be accepted for this test.

Information Sheet, including prices and CPT codes Back to the List
Consent Document  
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options  
CCM, cerebral cavernous malformations, cavernous angioma, cavernous hemangioma, KRIT1, CCM2, PDCD10, CCM1, CCM3, Hispanic, seizure, headache, stroke, hemorrhage, epilepsy

© 2000 - 2012 GeneDx. All rights reserved.