Familial cerebral cavernous malformation in a Filipino family

Maria Veronica  P. Comandao,; Christopher  O. Concepcion,

Familial cerebral cavernous malformation in a Filipino family

Maria Veronica P Comandao | Christopher O Concepcion

Abstract:

Cerebral cavernous malformation (CCM) is a type of vascular malformations characterized by the absence of intervening brain parenchyma. Cerebral cavernous malformations are of two forms, sporadic and familial. About 0.4-0.8% of the population are affected as assessed based on Magnetic Resonance Imaging (MRI) findings and postmortem findings. Three genetic mutations have been identified: CCM1, CCM2, CCM3, with an incidence of 40%, 40% and 20%, respectively. This study presents five members diagnosed with Familial CCM in a Filipino family. A 25-year-old male, from a low socio-economic background, was admitted due to a progressive generalized headache of 2 years’ duration, during which multiple brain lesions were observed on MRI. All members of the family became symptomatic before 30 years of age, and four out of the five members underwent surgery. However, molecular genetic testing was not performed as the patient could not afford it. The testing was not covered by the country’s insurance system, and it would have been an out-of-pocket expense. In patients diagnosed with cerebral cavernous malformations, a thorough clinical and family history is warranted accompanied by MRI-GRE (Magnetic Resonance Imaging - Gradient Echo) and MRI T2 help establish final diagnosis. Confirmation with molecular genetic testing should be offered to all members of the family for proper neurological and genetic care.

References:

Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, et al. The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 1994;80(3):422-32. doi:10.3171/ jns.1994.80.3.0422.
Moriarity JL, Wetzel M, Clatterbuck RE, Javedan S, Sheppard J, Hoenig-Rigamonti K, et al. The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 1999;44(6):1166-71. doi:10.1227/00006123-199906000-00003.
Washington CW, McCoy KE, Zipfel GJ. Update on the natural history of cavernous malformations and factors predicting aggressive clinical presentation. Neurosurg Focus 2010;29(3):E8. doi:10.3171/2010.5.focus10149.
Yadla S, Jabbour PM, Shenkar R, Shi C, Campbell PG, Awad IA. Cerebral cavernous malformations as a disease of vascular permeability: from bench to bedside with caution. Neurosurg Focus 2010;29(3):E4. doi:10.3171/2010.5.focus10121.
Labauge P. Familial forms of central nervous system cavernomas: from recognition to gene therapy. Neurochirurgie 2007;53:152-5.
Aiba T, Tanaka R, Koike T, Kameyama S, Takeda N, Komata T. Natural history of intracranial cavernous malformations. J Neurosurg 1995;83(1):56-9. doi:10.3171/ jns.1995.83.1.0056.
Batra S, Lin D, Recinos PF, Zhang J, Rigamonti D. Cavernous malformations: natural history, diagnosis and treatment. Nat Rev Neurol 2009;5(12):659-70. doi:10.1038/nrneurol.2009.177.
Simard JM, Garcia-Bengochea F, Ballinger WE, Mickle JP, Quisling RG. Cavernous angioma: a review of 126 collected and 12 new clinical cases. Neurosurgery 1986;18(2):203-10. doi:10.1097/00006123-198602000- 00008.
Wakai S, Ueda Y, Inoh S, Nagai M. Angiographically occult angiomas. Neurosurgery 1985;17(4):549-54. doi:10.1097/00006123-198510000-00003.
Tagle P, Huete I, Méndez J, Villar SD. Intracranial cavernous angioma: presentation and management. J Neurosurg 1986;64(5):720-3. doi:10.3171/jns.1986.64.5.0720.
Dubovsky J, Zabramski JM, Kurth J, Spetzler RF, Rich SS, Orr HT, et al. A gene responsible for cavernous malformations of the brain maps to chromosome 7q. Hum Mol Genet 1995;4(3):453-8. doi:10.1093/hmg/4.3.453.
Denier C, Labauge P, Brunereau L, Cavé-Riant F, Marchelli F, Arnoult M, et al. Clinical features of cerebral cavernous malformations patients with KRIT1 mutations. Ann Neurol 2003;55(2):213-20. doi:10.1002/ana.10804.
Denier C, Goutagny S, Labauge P, Krivosic V, Arnoult M, Cousin A, et al. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet 2004;74(2):326-37. doi:10.1086/381718
Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M, et al. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol 2006;60(5):550-6. doi:10.1002/ana.20947
Günel M, Awad IA, Finberg K, Anson JA, Steinberg GK, Batjer HH, et al. A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. N Engl J Med 1996;334(15):946-51. doi:10.1056/ nejm199604113341503.
Nagy G, Kemeny AA. Stereotactic radiosurgery of intracranial cavernous malformations. Neurosurg Clin N Am 2013;24(4):583-91.
Chalouhi N, Dumont AS, Randazzo C, Tjoumakaris S, Gonzalez LF, Rosenwasser R, et al. Management of incidentally discovered intracranial vascular abnormalities. Neurosurg Focus 2011;31(6):E1. doi:10.3171/2011.9.focus11200.