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CEREBRAL CAVERNOUS MALFORMATIONS 5(CCM5)

MedGen UID:
1055605
Concept ID:
CN378746
Disease or Syndrome
Synonym: CCM5
 
Gene (location): MAP3K3 (17q23.3)
 
OMIM®: 621032

Definition

Cerebral cavernous malformations and spinal cord cavernous malformations are common vascular abnormalities of the CNS that can lead to seizure, hemorrhage, and other neurologic defects (summary by Ren et al., 2023). For a general phenotypic description and a discussion of genetic heterogeneity of cerebral cavernous malformations, see CCM1 (116860). [from OMIM]

Professional guidelines

PubMed

Bubenikova A, Skalicky P, Benes V Jr, Benes V Sr, Bradac O
J Neurol Neurosurg Psychiatry 2022 May;93(5):475-480. Epub 2022 Mar 10 doi: 10.1136/jnnp-2021-328658. PMID: 35273070
Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K
Neurosurgery 2017 May 1;80(5):665-680. doi: 10.1093/neuros/nyx091. PMID: 28387823Free PMC Article
Gross BA, Du R
Expert Rev Neurother 2015;15(7):771-7. Epub 2015 Jun 22 doi: 10.1586/14737175.2015.1055323. PMID: 26098013

Recent clinical studies

Etiology

Mantziaris G, Dumot C, Pikis S, Peker S, Samanci Y, Ardor GD, Nabeel AM, Reda WA, Tawadros SR, Abdel Karim K, El-Shehaby AMN, Emad Eldin RM, Elazzazi AH, Sheehan D, Sheehan K, Martínez Moreno N, Martínez Álvarez R, Liscak R, May J, Tripathi M, Rajput A, Kumar N, Kaur R, Alzate JD, Kondziolka D, Dayawansa S, Sheehan JP
J Neurosurg Pediatr 2024 Apr 1;33(4):315-322. Epub 2024 Jan 5 doi: 10.3171/2023.11.PEDS23402. PMID: 38181511
Lanfranconi S, Scola E, Meessen JMTA, Pallini R, Bertani GA, Al-Shahi Salman R, Dejana E, Latini R; Treat_CCM Investigators
Lancet Neurol 2023 Jan;22(1):35-44. Epub 2022 Nov 17 doi: 10.1016/S1474-4422(22)00409-4. PMID: 36403580
Harris L, Poorthuis MHF, Grover P, Kitchen N, Al-Shahi Salman R
Neurosurg Rev 2022 Feb;45(1):231-241. Epub 2021 Jun 30 doi: 10.1007/s10143-021-01591-5. PMID: 34191202
Idiculla PS, Gurala D, Philipose J, Rajdev K, Patibandla P
Eur Neurol 2020;83(4):360-368. Epub 2020 Jul 30 doi: 10.1159/000508748. PMID: 32731220
Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K
Neurosurgery 2017 May 1;80(5):665-680. doi: 10.1093/neuros/nyx091. PMID: 28387823Free PMC Article

Diagnosis

Mantziaris G, Dumot C, Pikis S, Peker S, Samanci Y, Ardor GD, Nabeel AM, Reda WA, Tawadros SR, Abdel Karim K, El-Shehaby AMN, Emad Eldin RM, Elazzazi AH, Sheehan D, Sheehan K, Martínez Moreno N, Martínez Álvarez R, Liscak R, May J, Tripathi M, Rajput A, Kumar N, Kaur R, Alzate JD, Kondziolka D, Dayawansa S, Sheehan JP
J Neurosurg Pediatr 2024 Apr 1;33(4):315-322. Epub 2024 Jan 5 doi: 10.3171/2023.11.PEDS23402. PMID: 38181511
Koester SW, Rhodenhiser EG, Dabrowski SJ, Benner D, Rumalla K, Scherschinski L, Catapano JS, Graffeo CS, Srinivasan VM, Lawton MT
World Neurosurg 2023 Nov;179:222-232.e2. Epub 2023 Aug 17 doi: 10.1016/j.wneu.2023.08.036. PMID: 37595838
Idiculla PS, Gurala D, Philipose J, Rajdev K, Patibandla P
Eur Neurol 2020;83(4):360-368. Epub 2020 Jul 30 doi: 10.1159/000508748. PMID: 32731220
Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K
Neurosurgery 2017 May 1;80(5):665-680. doi: 10.1093/neuros/nyx091. PMID: 28387823Free PMC Article
Mondejar R, Lucas M
Neurologia 2017 Oct;32(8):540-545. Epub 2015 Aug 21 doi: 10.1016/j.nrl.2015.07.001. PMID: 26304651

Therapy

Mantziaris G, Dumot C, Pikis S, Peker S, Samanci Y, Ardor GD, Nabeel AM, Reda WA, Tawadros SR, Abdel Karim K, El-Shehaby AMN, Emad Eldin RM, Elazzazi AH, Sheehan D, Sheehan K, Martínez Moreno N, Martínez Álvarez R, Liscak R, May J, Tripathi M, Rajput A, Kumar N, Kaur R, Alzate JD, Kondziolka D, Dayawansa S, Sheehan JP
J Neurosurg Pediatr 2024 Apr 1;33(4):315-322. Epub 2024 Jan 5 doi: 10.3171/2023.11.PEDS23402. PMID: 38181511
Lanfranconi S, Scola E, Meessen JMTA, Pallini R, Bertani GA, Al-Shahi Salman R, Dejana E, Latini R; Treat_CCM Investigators
Lancet Neurol 2023 Jan;22(1):35-44. Epub 2022 Nov 17 doi: 10.1016/S1474-4422(22)00409-4. PMID: 36403580
Bubenikova A, Skalicky P, Benes V Jr, Benes V Sr, Bradac O
J Neurol Neurosurg Psychiatry 2022 May;93(5):475-480. Epub 2022 Mar 10 doi: 10.1136/jnnp-2021-328658. PMID: 35273070
Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL, Mabray MC, Vigil C, Tang AT, Kahn ML, Yonas H, Lawton MT, Kim H, Morrison L
Stroke 2019 May;50(5):1294-1301. doi: 10.1161/STROKEAHA.118.022314. PMID: 30909834Free PMC Article
Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K
Neurosurgery 2017 May 1;80(5):665-680. doi: 10.1093/neuros/nyx091. PMID: 28387823Free PMC Article

Prognosis

Mantziaris G, Dumot C, Pikis S, Peker S, Samanci Y, Ardor GD, Nabeel AM, Reda WA, Tawadros SR, Abdel Karim K, El-Shehaby AMN, Emad Eldin RM, Elazzazi AH, Sheehan D, Sheehan K, Martínez Moreno N, Martínez Álvarez R, Liscak R, May J, Tripathi M, Rajput A, Kumar N, Kaur R, Alzate JD, Kondziolka D, Dayawansa S, Sheehan JP
J Neurosurg Pediatr 2024 Apr 1;33(4):315-322. Epub 2024 Jan 5 doi: 10.3171/2023.11.PEDS23402. PMID: 38181511
Koester SW, Rhodenhiser EG, Dabrowski SJ, Benner D, Rumalla K, Scherschinski L, Catapano JS, Graffeo CS, Srinivasan VM, Lawton MT
World Neurosurg 2023 Nov;179:222-232.e2. Epub 2023 Aug 17 doi: 10.1016/j.wneu.2023.08.036. PMID: 37595838
Dammann P, Santos AN, Wan XY, Zhu Y, Sure U
Neurosurg Clin N Am 2022 Oct;33(4):449-460. Epub 2022 Sep 11 doi: 10.1016/j.nec.2022.05.001. PMID: 36229132
Idiculla PS, Gurala D, Philipose J, Rajdev K, Patibandla P
Eur Neurol 2020;83(4):360-368. Epub 2020 Jul 30 doi: 10.1159/000508748. PMID: 32731220
Goldstein HE, Solomon RA
Handb Clin Neurol 2017;143:241-247. doi: 10.1016/B978-0-444-63640-9.00023-0. PMID: 28552146

Clinical prediction guides

Sandmann ACA, Kempeneers MA, van den Berg R, Verbaan D, Vandertop WP, Coutinho JM
Eur Stroke J 2024 Sep;9(3):667-675. Epub 2024 Apr 16 doi: 10.1177/23969873241246868. PMID: 38624046Free PMC Article
Flemming KD, Kim H, Hage S, Mandrekar J, Kinkade S, Girard R, Torbey M, Huang J, Huston J 3rd, Shu Y, Lanzino G, Selwyn R, Hart B, Mabray M, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson R, Koenig JI, Carroll T, Hanley D, Awad I
Stroke 2024 Jan;55(1):22-30. Epub 2023 Dec 22 doi: 10.1161/STROKEAHA.123.044068. PMID: 38134268Free PMC Article
Lanfranconi S, Scola E, Meessen JMTA, Pallini R, Bertani GA, Al-Shahi Salman R, Dejana E, Latini R; Treat_CCM Investigators
Lancet Neurol 2023 Jan;22(1):35-44. Epub 2022 Nov 17 doi: 10.1016/S1474-4422(22)00409-4. PMID: 36403580
Gross BA, Du R
Expert Rev Neurother 2015;15(7):771-7. Epub 2015 Jun 22 doi: 10.1586/14737175.2015.1055323. PMID: 26098013
Choquet H, Pawlikowska L, Lawton MT, Kim H
J Neurosurg Sci 2015 Sep;59(3):211-20. Epub 2015 Apr 22 PMID: 25900426Free PMC Article

Recent systematic reviews

Koester SW, Rhodenhiser EG, Dabrowski SJ, Benner D, Rumalla K, Scherschinski L, Catapano JS, Graffeo CS, Srinivasan VM, Lawton MT
World Neurosurg 2023 Nov;179:222-232.e2. Epub 2023 Aug 17 doi: 10.1016/j.wneu.2023.08.036. PMID: 37595838
Harris L, Poorthuis MHF, Grover P, Kitchen N, Al-Shahi Salman R
Neurosurg Rev 2022 Feb;45(1):231-241. Epub 2021 Jun 30 doi: 10.1007/s10143-021-01591-5. PMID: 34191202
Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B, Kim H, Jusue-Torres I, Kondziolka D, Lee C, Morrison L, Rigamonti D, Rebeiz T, Tournier-Lasserve E, Waggoner D, Whitehead K
Neurosurgery 2017 May 1;80(5):665-680. doi: 10.1093/neuros/nyx091. PMID: 28387823Free PMC Article
Poorthuis MH, Klijn CJ, Algra A, Rinkel GJ, Al-Shahi Salman R
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1319-23. Epub 2014 Mar 25 doi: 10.1136/jnnp-2013-307349. PMID: 24667206
Gross BA, Batjer HH, Awad IA, Bendok BR
Neurosurgery 2009 May;64(5):E805-18; discussion E818. doi: 10.1227/01.NEU.0000343668.44288.18. PMID: 19404127

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