Format

Send to:

Choose Destination

Cerebral cavernous malformation(CCM)

MedGen UID:
349362
Concept ID:
C1861784
Disease or Syndrome
Synonyms: CAVERNOUS ANGIOMA, FAMILIAL; CAVERNOUS ANGIOMATOUS MALFORMATIONS; Cavernous Hemangioma of Brain; CCM; CEREBRAL CAPILLARY MALFORMATIONS; Cerebral cavernous hemangioma (type); CEREBRAL CAVERNOUS MALFORMATIONS; Familial Cerebral Cavernous Malformation
Modes of inheritance:
Heterogeneous
MedGen UID:
67020
Concept ID:
C0242960
Organism Attribute
Source: HPO
The production of the same or similar phenotypes (observed biochemical, physiological, and morphological characteristics of a person determined by his/her genotype) by different genetic mechanisms. There are two types: (1) allelic heterogeneity - when different alleles at a locus can produce variable expression of a condition; and (2) locus heterogeneity - the term used to describe disease in which mutations at different loci can produce the same disease phenotype.
Autosomal dominant inheritance
MedGen UID:
892334
Concept ID:
CN000007
Functional Concept
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): KRIT1 (7q21.2)
OMIM®: 116860

Disease characteristics

Excerpted from the GeneReview: Cerebral Cavernous Malformation, Familial
Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord comprising closely clustered, enlarged capillary channels (caverns) with a single layer of endothelium without mature vessel wall elements or normal intervening brain parenchyma. The diameter of CCMs ranges from a few millimeters to several centimeters. CCMs increase or decrease in size and increase in number over time. Hundreds of lesions may be identified, depending on the person’s age and the quality and type of brain imaging used. Although CCMs have been reported in infants and children, the majority become evident between the second and fifth decades with findings such as seizures, focal neurologic deficits, nonspecific headaches, and cerebral hemorrhage. Up to 50% of individuals with FCCM remain symptom free throughout their lives. Cutaneous vascular lesions are found in 9% of those with familial cerebral cavernous malformations (FCCM; see Diagnosis/testing) and retinal vascular lesions in almost 5%. [from GeneReviews]
Authors:
Leslie Morrison  |  Amy Akers   view full author information

Additional descriptions

From OMIM
Cerebral cavernous angiomas are relatively rare vascular malformations that may involve any part of the central nervous system. Cerebral cavernous angiomas are to be distinguished from cerebral arteriovenous malformations (106070, 108010). CCMs are venous and not demonstrable by arteriography; hence they are referred to as angiographically silent. Capillary hemangiomas (602089) are classified as distinct from vascular malformations in that hemangiomas are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. Hemangiomas develop shortly after birth. In contrast, vascular malformations are present from birth, tend to grow with the individual, do not regress, and show normal rates of endothelial cell turnover (Mulliken and Young, 1988). Genetic Heterogeneity of CCM CCM2 (603284) is caused by mutation in the CCM2/malcavernin gene (607929), and CCM3 (603285) is caused by mutation in the PDCD10 gene (609118). Evidence suggests that a 2-hit mechanism involving biallelic germline and somatic mutations is responsible for CCM1 pathogenesis, see PATHOGENESIS and MOLECULAR GENETICS sections.  http://www.omim.org/entry/116860
From GHR
Cerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral).Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time.There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation.  https://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation

Clinical features

Intracranial hemorrhage
MedGen UID:
505138
Concept ID:
CN001967
Finding
Hemorrhage occurring within the skull.
Retinal vascular malformation
MedGen UID:
350100
Concept ID:
C1861791
Finding
Hepatic vascular malformations
MedGen UID:
350099
Concept ID:
C1861790
Finding
Retinal vascular malformation
MedGen UID:
350100
Concept ID:
C1861791
Finding
Intracranial hemorrhage
MedGen UID:
505138
Concept ID:
CN001967
Finding
Hemorrhage occurring within the skull.
Hepatic vascular malformations
MedGen UID:
350099
Concept ID:
C1861790
Finding
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Seizures are symptoms of a brain problem. They happen because of sudden, abnormal electrical activity in the brain. When people think of seizures, they often think of convulsions in which a person's body shakes rapidly and uncontrollably. Not all seizures cause convulsions. There are many types of seizures and some have mild symptoms. Seizures fall into two main groups. Focal seizures, also called partial seizures, happen in just one part of the brain. Generalized seizures are a result of abnormal activity on both sides of the brain. . Most seizures last from 30 seconds to 2 minutes and do not cause lasting harm. However, it is a medical emergency if seizures last longer than 5 minutes or if a person has many seizures and does not wake up between them. Seizures can have many causes, including medicines, high fevers, head injuries and certain diseases. People who have recurring seizures due to a brain disorder have epilepsy. . NIH: National Institute of Neurological Disorders and Stroke.
Headache
MedGen UID:
472355
Concept ID:
C2096315
Finding
Intracranial hemorrhage
MedGen UID:
505138
Concept ID:
CN001967
Finding
Hemorrhage occurring within the skull.
Intracranial hemorrhage
MedGen UID:
505138
Concept ID:
CN001967
Finding
Hemorrhage occurring within the skull.
Hepatic vascular malformations
MedGen UID:
350099
Concept ID:
C1861790
Finding
Abnormality of the musculature
MedGen UID:
867380
Concept ID:
C4021745
Anatomical Abnormality
Abnormality originating in one or more muscles, i.e., of the set of muscles of body.
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
The presence of calcium deposition within brain structures.
Abnormality of the skin
MedGen UID:
11449
Concept ID:
C0037268
Finding
An abnormality of the skin.

Suggested Reading

PubMed

Al-Shahi Salman R, Hall JM, Horne MA, Moultrie F, Josephson CB, Bhattacharya JJ, Counsell CE, Murray GD, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP; Scottish Audit of Intracranial Vascular Malformations (SAIVMs) collaborators
Lancet Neurol 2012 Mar;11(3):217-24. Epub 2012 Jan 31 doi: 10.1016/S1474-4422(12)70004-2. [Epub ahead of print] PMID: 22297119
Al-Shahi Salman R, Berg MJ, Morrison L, Awad IA; Angioma Alliance Scientific Advisory Board
Stroke 2008 Dec;39(12):3222-30. Epub 2008 Oct 30 doi: 10.1161/STROKEAHA.108.515544. [Epub ahead of print] PMID: 18974380

Recent clinical studies

Etiology

Trapani E, Retta SF
J Neurosurg Sci 2015 Sep;59(3):201-9. Epub 2015 Apr 21 [Epub ahead of print] PMID: 25896717
Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J, Walker AE, Goitre L, Delle Monache S, Retta SF, Shiu YT, Grossmann AH, Thomas KR, Donato AJ, Lesniewski LA, Whitehead KJ, Li DY
Circulation 2015 Jan 20;131(3):289-99. Epub 2014 Dec 8 doi: 10.1161/CIRCULATIONAHA.114.010403. [Epub ahead of print] PMID: 25486933Free PMC Article
Shenkar R, Shi C, Rebeiz T, Stockton RA, McDonald DA, Mikati AG, Zhang L, Austin C, Akers AL, Gallione CJ, Rorrer A, Gunel M, Min W, Marcondes de Souza J, Lee C, Marchuk DA, Awad IA
Genet Med 2015 Mar;17(3):188-96. Epub 2014 Aug 14 doi: 10.1038/gim.2014.97. [Epub ahead of print] PMID: 25122144Free PMC Article
Choquet H, Pawlikowska L, Nelson J, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H; Brain Vascular Malformation Consortium (BVMC) Study
Cerebrovasc Dis 2014;38(6):433-40. Epub 2014 Dec 3 doi: 10.1159/000369200. [Epub ahead of print] PMID: 25472749Free PMC Article
Jeon JS, Kim JE, Chung YS, Oh S, Ahn JH, Cho WS, Son YJ, Bang JS, Kang HS, Sohn CH, Oh CW
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1366-70. Epub 2014 Mar 28 doi: 10.1136/jnnp-2013-306844. [Epub ahead of print] PMID: 24681702

Diagnosis

Ruan D, Yu XB, Shrestha S, Wang L, Chen G
PLoS One 2015;10(8):e0136619. Epub 2015 Aug 25 doi: 10.1371/journal.pone.0136619. PMID: 26305879Free PMC Article
Trapani E, Retta SF
J Neurosurg Sci 2015 Sep;59(3):201-9. Epub 2015 Apr 21 [Epub ahead of print] PMID: 25896717
Jeon JS, Kim JE, Chung YS, Oh S, Ahn JH, Cho WS, Son YJ, Bang JS, Kang HS, Sohn CH, Oh CW
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1366-70. Epub 2014 Mar 28 doi: 10.1136/jnnp-2013-306844. [Epub ahead of print] PMID: 24681702
Tan H, Liu T, Wu Y, Thacker J, Shenkar R, Mikati AG, Shi C, Dykstra C, Wang Y, Prasad PV, Edelman RR, Awad IA
Invest Radiol 2014 Jul;49(7):498-504. doi: 10.1097/RLI.0000000000000043. PMID: 24619210Free PMC Article
Nahrir S, Al-Hameed MH, Al-Sinaidi OA, Al Shakweer W
BMJ Case Rep 2013 Nov 21;2013 doi: 10.1136/bcr-2013-009417. PMID: 24265337Free PMC Article

Therapy

Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J, Walker AE, Goitre L, Delle Monache S, Retta SF, Shiu YT, Grossmann AH, Thomas KR, Donato AJ, Lesniewski LA, Whitehead KJ, Li DY
Circulation 2015 Jan 20;131(3):289-99. Epub 2014 Dec 8 doi: 10.1161/CIRCULATIONAHA.114.010403. [Epub ahead of print] PMID: 25486933Free PMC Article
Eisa-Beygi S, Wen XY, Macdonald RL
Stroke 2014 Jun;45(6):1859-61. Epub 2014 May 6 doi: 10.1161/STROKEAHA.114.005132. [Epub ahead of print] PMID: 24803598
Zakaria Z, Kaliaperumal C, Caird J, Sattar M
BMJ Case Rep 2012 Nov 30;2012 doi: 10.1136/bcr-2012-007508. PMID: 23203183Free PMC Article
Schreuder T, Te Lintelo M, Kubat B, Koehler P
J Neurol 2010 Mar;257(3):349-53. Epub 2009 Sep 24 doi: 10.1007/s00415-009-5322-0. [Epub ahead of print] PMID: 19777285
Pozzati E, Zucchelli M, Marliani AF, Riccioli LA
Neurosurg Focus 2006 Jul 15;21(1):e15. PMID: 16859253

Prognosis

Trapani E, Retta SF
J Neurosurg Sci 2015 Sep;59(3):201-9. Epub 2015 Apr 21 [Epub ahead of print] PMID: 25896717
Choquet H, Pawlikowska L, Nelson J, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H; Brain Vascular Malformation Consortium (BVMC) Study
Cerebrovasc Dis 2014;38(6):433-40. Epub 2014 Dec 3 doi: 10.1159/000369200. [Epub ahead of print] PMID: 25472749Free PMC Article
Mondéjar R, Solano F, Rubio R, Delgado M, Pérez-Sempere A, González-Meneses A, Vendrell T, Izquierdo G, Martinez-Mir A, Lucas M
PLoS One 2014;9(1):e86286. Epub 2014 Jan 23 doi: 10.1371/journal.pone.0086286. PMID: 24466005Free PMC Article
Dammann P, Hehr U, Weidensee S, Zhu Y, Gerlach R, Sure U
Neurosurg Rev 2013 Jul;36(3):483-6. Epub 2013 Apr 13 doi: 10.1007/s10143-013-0456-z. [Epub ahead of print] PMID: 23584803
Zakaria Z, Kaliaperumal C, Caird J, Sattar M
BMJ Case Rep 2012 Nov 30;2012 doi: 10.1136/bcr-2012-007508. PMID: 23203183Free PMC Article

Clinical prediction guides

Choquet H, Pawlikowska L, Nelson J, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H; Brain Vascular Malformation Consortium (BVMC) Study
Cerebrovasc Dis 2014;38(6):433-40. Epub 2014 Dec 3 doi: 10.1159/000369200. [Epub ahead of print] PMID: 25472749Free PMC Article
Jeon JS, Kim JE, Chung YS, Oh S, Ahn JH, Cho WS, Son YJ, Bang JS, Kang HS, Sohn CH, Oh CW
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1366-70. Epub 2014 Mar 28 doi: 10.1136/jnnp-2013-306844. [Epub ahead of print] PMID: 24681702
Mondéjar R, Solano F, Rubio R, Delgado M, Pérez-Sempere A, González-Meneses A, Vendrell T, Izquierdo G, Martinez-Mir A, Lucas M
PLoS One 2014;9(1):e86286. Epub 2014 Jan 23 doi: 10.1371/journal.pone.0086286. PMID: 24466005Free PMC Article
Choquet H, Nelson J, Pawlikowska L, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H
Cerebrovasc Dis 2014;37(1):57-63. Epub 2013 Dec 21 doi: 10.1159/000356839. [Epub ahead of print] PMID: 24401931Free PMC Article
D'Angelo R, Scimone C, Rinaldi C, Trimarchi G, Italiano D, Bramanti P, Amato A, Sidoti A
Int J Mol Med 2012 Jun;29(6):1113-20. Epub 2012 Feb 28 doi: 10.3892/ijmm.2012.927. [Epub ahead of print] PMID: 22378217

Recent systematic reviews

Ruan D, Yu XB, Shrestha S, Wang L, Chen G
PLoS One 2015;10(8):e0136619. Epub 2015 Aug 25 doi: 10.1371/journal.pone.0136619. PMID: 26305879Free PMC Article
Poorthuis M, Samarasekera N, Kontoh K, Stuart I, Cope B, Kitchen N, Al-Shahi Salman R
Acta Neurochir (Wien) 2013 Apr;155(4):643-9. Epub 2013 Jan 31 doi: 10.1007/s00701-013-1621-4. [Epub ahead of print] PMID: 23371401

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...