Cerebral Cavernous Malformation (CCM)

Cerebral cavernous malformations (CCM) are predominantly central nervous system (CNS) vascular lesions formed by a cluster of grossly dilated blood vessels. Each vessel is comprised of a single layer of epithelium without normal intervening brain parenchyma or vascular support cells. Symptoms typically present in the 2nd-5th decades and can include seizures, focal neurological deficits, chronic headaches, epilepsy, stroke, and cerebral hemorrhage. Interfamilial and intrafamilial variability of symptoms has been noted. Individuals may be clinically asymptomatic; MRI may be necessary to diagnose asymptomatic lesions in at-risk individuals. Although the vascular anomalies primarily affect the CNS, lesions also have been reported in the retina (Labauge et al, 2006; Davenport et al, 2001) and skin, as hyperkeratotic cutaneous capillary-venous malformations (Chen et al, 2002; Eerola et al, 2000). CCM occurs in 0.1-0.5% of the general population and can occur isolated or as a familial form. Familial CCM is defined as the presence of CCM in at least two family members, and/or the presence of an identified disease causing mutation in one of the three genes known to be associated with CCM (KRIT1, CCM2, PDCD10), and/or the presence of multiple CCMs in an individual. The prevalence of the familial form is estimated to be as high as 50% within the Southwest American Hispanic population (due to a founder mutation in the KRIT1 gene) and as high as 10-40% within the Caucasian population (Riant et al, 2010). Penetrance is incomplete, which may account for unrecognized familial forms initially thought to be sporadic

Tests Available

Forms and Documents

Test Details

KRIT1
  • Confirmation of a clinical diagnosis
  • Identification of family members at-risk for cerebral cavernous malformations (CCMs)
  • Recurrence risk assessment
  • Prenatal diagnosis in families with a known mutation
  • Capillary Sequencing

Ordering

4181
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 747.81 Anomalies of cerebrovascular system, Arteriovenous malformation of brain, Cerebral arteriovenous aneurysm, congenital Congenital anomalies of cerebral vessels
  • 228 Hemangioma and lymphangioma,
  • 747.6 Other anomalies of peripheral vascular system, Absence of artery or vein, NEC Anomaly of artery or vein, NEC Atresia of artery or vein, NEC Arteriovenous aneurysm (peripheral), Arteriovenous malformation of the peripheral vascular system Congenital: aneurysm (peripheral) phlebectasia stricture, artery varix Multiple renal arteries Excludes: anomalies of: cerebral vessels (747.81) pulmonary artery (747.3) congenital retinal aneurysm (743.58) hemangioma (228.00-228.09) lymphangioma (228.1)
  • 325 Phlebitis and thrombophlebitis of intracranial venous sinuses, Embolism of cavernous, lateral, or other intracranial or unspecified intracranial venous sinu,s Endophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Phlebitis, septic or suppurative of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombosis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Excludes: that specified as: complicating pregnancy, childbirth, or the puerperium (671.5) of nonpyogenic origin (437.6)
* For price inquiries please email zebras@genedx.com

References

  1. Riant et al. (2010) FEBS J 277:1070-1075
  2. Denier et al. (2006) Ann Neurol 60:550-556
  3. Stahl et al. (2008) Hum Mutat 29(5):709-717
  4. Liquori et al. (2007) Am J Hum Genet 80:69-75
  5. Faurobert and Albiges-Rizo. (2010) FEBS J 277:1084-1096
  6. Labauge et al. (2006) Arch Ophthalmol 124:885-886
  7. Eerola et al. (2000) Hum Mol Genet 9(9):1351-1355
  8. Davenport et al. (2001) Neurology 56:540-543
  9. Chen et al. (2002) J Neurol Sci 196:91-96
  10. Cavé-Riant et al. (2002) Eur J Hum Genet 10:733-740

Forms and Documents

Test Details

CCM2, KRIT1, PDCD10
  • Confirmation of a clinical diagnosis
  • Identification of family members at-risk for cerebral cavernous malformations (CCMs)
  • Recurrence risk assessment
  • Prenatal diagnosis in families with a known mutation
  • Capillary Sequencing
  • Exon Array CGH

Ordering

4182
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 747.81 Anomalies of cerebrovascular system, Arteriovenous malformation of brain, Cerebral arteriovenous aneurysm, congenital Congenital anomalies of cerebral vessels
  • 228 Hemangioma and lymphangioma,
  • 747.6 Other anomalies of peripheral vascular system, Absence of artery or vein, NEC Anomaly of artery or vein, NEC Atresia of artery or vein, NEC Arteriovenous aneurysm (peripheral), Arteriovenous malformation of the peripheral vascular system Congenital: aneurysm (peripheral) phlebectasia stricture, artery varix Multiple renal arteries Excludes: anomalies of: cerebral vessels (747.81) pulmonary artery (747.3) congenital retinal aneurysm (743.58) hemangioma (228.00-228.09) lymphangioma (228.1)
  • 325 Phlebitis and thrombophlebitis of intracranial venous sinuses, Embolism of cavernous, lateral, or other intracranial or unspecified intracranial venous sinu,s Endophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Phlebitis, septic or suppurative of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombosis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Excludes: that specified as: complicating pregnancy, childbirth, or the puerperium (671.5) of nonpyogenic origin (437.6)
* For price inquiries please email zebras@genedx.com

References

  1. Riant et al. (2010) FEBS J 277:1070-1075
  2. Stahl et al. (2008) Hum Mutat 29(5):709-717
  3. Labauge et al. (2006) Arch Ophthalmol 124:885-886
  4. Liquori et al. (2007) Am J Hum Genet 80:69-75
  5. Faurobert and Albiges-Rizo. (2010) FEBS J 277:1084-1096
  6. Denier et al. (2006) Ann Neurol 60:550-556
  7. Eerola et al. (2000) Hum Mol Genet 9(9):1351-13
  8. Chen et al. (2002) J Neurol Sci 196:91-96
  9. Davenport et al. (2001) Neurology 56:540-543
  10. Cavé-Riant et al. (2002) Eur J Hum Genet 10:733-740

Forms and Documents

Test Details

CCM2
  • Confirmation of a clinical diagnosis
  • Identification of family members at-risk for cerebral cavernous malformations (CCMs)
  • Recurrence risk assessment
  • Prenatal diagnosis in families with a known mutation
  • Capillary Sequencing

Ordering

419
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 747.81 Anomalies of cerebrovascular system, Arteriovenous malformation of brain, Cerebral arteriovenous aneurysm, congenital Congenital anomalies of cerebral vessels
  • 228 Hemangioma and lymphangioma,
  • 747.6 Other anomalies of peripheral vascular system, Absence of artery or vein, NEC Anomaly of artery or vein, NEC Atresia of artery or vein, NEC Arteriovenous aneurysm (peripheral), Arteriovenous malformation of the peripheral vascular system Congenital: aneurysm (peripheral) phlebectasia stricture, artery varix Multiple renal arteries Excludes: anomalies of: cerebral vessels (747.81) pulmonary artery (747.3) congenital retinal aneurysm (743.58) hemangioma (228.00-228.09) lymphangioma (228.1)
  • 325 Phlebitis and thrombophlebitis of intracranial venous sinuses, Embolism of cavernous, lateral, or other intracranial or unspecified intracranial venous sinu,s Endophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Phlebitis, septic or suppurative of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombosis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Excludes: that specified as: complicating pregnancy, childbirth, or the puerperium (671.5) of nonpyogenic origin (437.6)
* For price inquiries please email zebras@genedx.com

References

  1. Stahl et al. (2008) Hum Mutat 29(5):709-717
  2. Riant et al. (2010) FEBS J 277:1070-1075
  3. Liquori et al. (2007) Am J Hum Genet 80:69-75
  4. Labauge et al. (2006) Arch Ophthalmol 124:885-886
  5. Faurobert and Albiges-Rizo. (2010) FEBS J 277:1084-1096
  6. Eerola et al. (2000) Hum Mol Genet 9(9):1351-1355
  7. Denier et al. (2006) Ann Neurol 60:550-556
  8. Davenport et al. (2001) Neurology 56:540-543
  9. Chen et al. (2002) J Neurol Sci 196:91-96
  10. Cavé-Riant et al. (2002) Eur J Hum Genet 10:733-740

Forms and Documents

Test Details

PDCD10
  • Confirmation of a clinical diagnosis
  • Identification of family members at-risk for cerebral cavernous malformations (CCMs)
  • Recurrence risk assessment
  • Prenatal diagnosis in families with a known mutation
  • Capillary Sequencing

Ordering

420
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Eerola et al. (2000) Hum Mol Genet 9(9):1351-1355
  2. Stahl et al. (2008) Hum Mutat 29(5):709-717
  3. Riant et al. (2010) FEBS J 277:1070-1075
  4. Liquori et al. (2007) Am J Hum Genet 80:69-75
  5. Labauge et al. (2006) Arch Ophthalmol 124:885-886
  6. Faurobert and Albiges-Rizo. (2010) FEBS J 277:1084-1096
  7. Denier et al. (2006) Ann Neurol 60:550-556
  8. Davenport et al. (2001) Neurology 56:540-543
  9. Chen et al. (2002) J Neurol Sci 196:91-96
  10. Cavé-Riant et al. (2002) Eur J Hum Genet 10:733-740

Forms and Documents

Test Details

CCM2, KRIT1, PDCD10
  • Confirmation of a clinical diagnosis
  • Identification of family members at-risk for cerebral cavernous malformations (CCMs)
  • Recurrence risk assessment
  • Prenatal diagnosis in families with a known mutation
  • Capillary Sequencing
  • Exon Array CGH

Ordering

526
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 747.81 Anomalies of cerebrovascular system, Arteriovenous malformation of brain, Cerebral arteriovenous aneurysm, congenital Congenital anomalies of cerebral vessels
  • 228 Hemangioma and lymphangioma,
  • 747.6 Other anomalies of peripheral vascular system, Absence of artery or vein, NEC Anomaly of artery or vein, NEC Atresia of artery or vein, NEC Arteriovenous aneurysm (peripheral), Arteriovenous malformation of the peripheral vascular system Congenital: aneurysm (peripheral) phlebectasia stricture, artery varix Multiple renal arteries Excludes: anomalies of: cerebral vessels (747.81) pulmonary artery (747.3) congenital retinal aneurysm (743.58) hemangioma (228.00-228.09) lymphangioma (228.1)
  • 325 Phlebitis and thrombophlebitis of intracranial venous sinuses, Embolism of cavernous, lateral, or other intracranial or unspecified intracranial venous sinu,s Endophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Phlebitis, septic or suppurative of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombophlebitis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Thrombosis of cavernous, lateral, or other intracranial or unspecified intracranial venous sinus Excludes: that specified as: complicating pregnancy, childbirth, or the puerperium (671.5) of nonpyogenic origin (437.6)
* For price inquiries please email zebras@genedx.com

References

  1. Cavé-Riant et al. (2002) Eur J Hum Genet 10:733-740.
  2. Chen et al. (2002) J Neurol Sci 196:91-96.
  3. Davenport et al. (2001) Neurology 56:540-543.
  4. Denier et al. (2006) Ann Neurol 60:550-556.
  5. Eerola et al. (2000) Hum Mol Genet 9(9):1351-1355.
  6. Faurobert and Albiges-Rizo. (2010) FEBS J 277:1084-1096.
  7. Labauge et al. (2006) Arch Ophthalmol 124:885-886
  8. Liquori et al. (2007) Am J Hum Genet 80:69-75.
  9. Riant et al. (2010) FEBS J 277:1070-1075.
  10. Stahl et al. (2008) Hum Mutat 29(5):709- 717.