FaCD Online Syndrome Fact Sheet

Last updated: 28 Feb 2008

Name: Familial Cerebral Cavernous Angioma

Synonym: Cerebral Cavernous Malformations 1, 2 and 3, Familial Cavernous Angioma, Familial Cerebral Cavernomas

Mode of Inheritance: AD

Genes

CCM1/KRIT1, mapped to 7q11.2-q21
CCM2/MGC4607, mapped to 7p13
CCM3/PDCD10, mapped to 3q26.1

Tumor features

brain, cavernous hemangioma
hepatic hemangioma
retinal hemangioblastoma (hemangioma / angioma)
subcutaneous hemangioma

Non-tumor features

hyperkeratotic cutaneous capillary venous malformations

Comment

In this condition multiple cerebral cavernous angiomas (cavernomas) develop. These are closely clustered vessels with a single layer of endothelium. The walls of the vessels lack elastic tissue and smooth muscles. Patients with this condition may show no symptoms, or develop epilepsy, focal neurological deficits, bleeding from the cavernomas and headaches. The cavernomas can also be found subcutaneously, in the retina and in the liver. Age of onset shows a peak between 20 and 40 years. Less than 20 % manifest before the age of 10 years.[1-5;9;10]. A case for anticipation with respect to age of onset, not with respect to disease severity, in this disorder has been made by the International Familial Cavernous Angioma Study[6;7]. In 4 families with the disorder and linkage to the 7q locus, an association with hyperkeratotic cutaneous capillary venous malformations was observed[8].

References

[1] Drigo P, Mammi I, Battistella PA, Ricchieri G, Carollo C. Familial cerebral,hepatic and retinal cavernous angiomas: a new syndrome. Childs Nerv Syst 1994; 10:205-209.
[2] Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig-Rigamonti K, Knight JT, Spetzler RF. Cerebral cavernous malformations: incidence and familial occurrence. N Engl J Med 1988; 319(6):343-347.
[3] Steichen-Gersdorf E, Felber S, Fuchs W, Russeger L, Twerdy K. Familial cavernous angiomas of the brain: observations in a four generation family. J Pediat 1992; 151:861-863.
[4] Dellemijn PLI, Vanneste JAL. Cavernous angiomatosis of the central nervous system: usefulness of screening the family. Acta Neurol Scand 1993; 88:259-263.
[5] Bicknell JM, Carlow TJ, Kornfeld M, Stovring J, Turner S. Familial cavernous angiomas. Arch Neurol 1978; 35:746-749.
[6] Siegel AM, Andermann F, Badhwar A, Rouleau GA, Dam M, Hopf HC, Dichgans J, Sturzenegger M, Hopf NJ, Yasui N, Stepper F, Killer M, Vanneste JAL, Acciarri N, Drigo P, Christensen J, Braun V, Konu D, Andermann E. Anticipation in familial cavernous angioma: ascertainment bias or genetic cause. Acta Neurol Scand 98[6], 372-376. 1998.
[7] Siegel AM. Familial cavernous angioma: an unknown, known disease. Acta Neurol Scand 98[6], 369-371. 1998.
[8] Labauge P, Enjolras O, Bonerandi JJ, Laberge S, Dandurand M, Joujoux JM, Tournier-Lasserve E. An association between autosomal dominant cerebral cavernomas and a distinctive hyperkeratotic cutaneous vascular malformation in 4 families. Ann.Neurol. 45[2], 250-254. 1999.
[9] Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet neurology 2007; 6(3):237-44.
[10] Gault J, Sain S, Hu LJ, Awad IA. Spectrum of genotype and clinical manifestations in cerebral cavernous malformations. Neurosurgery 2006; 59(6):1278-84; discussion 1284-5.