====== Familial multiple cavernous malformation syndrome ======


Familial [[multiple cavernous malformation]] syndrome is uncommon, accounting for only a minority of [[cavernous malformation]]s.

===== Epidemiology =====

It has been more frequently reported in patients of Hispanic descent
((Brunereau L, Labauge P, Tournier-lasserve E et-al. Familial form of intracranial cavernous angioma: MR imaging findings in 51 families. French Society of Neurosurgery. Radiology. 2000;214 (1): 209-16.))

===== Clinical features =====

The presentation is most commonly with [[seizure]]s (38-55%) 
((Brunereau L, Labauge P, Tournier-lasserve E et-al. Familial form of intracranial cavernous angioma: MR imaging findings in 51 families. French Society of Neurosurgery. Radiology. 2000;214 (1): 209-16.))
and [[focal neurological deficit]]s while recurrent large hemorrhages and headaches are less frequently encountered. 

===== Pathology =====

In sporadic cases up to a third of [[cavernous malformation]]s are multiple. When familial the number of cavernomas is higher, typically five or more
((Brunereau L, Labauge P, Tournier-lasserve E et-al. Familial form of intracranial cavernous angioma: MR imaging findings in 51 families. French Society of Neurosurgery. Radiology. 2000;214 (1): 209-16.))
and may be as high as dozens and dozens.

Familial cases usually have an autosomal dominant pattern of inheritance with incomplete penetrance
((Brunereau L, Labauge P, Tournier-lasserve E et-al. Familial form of intracranial cavernous angioma: MR imaging findings in 51 families. French Society of Neurosurgery. Radiology. 2000;214 (1): 209-16.))
((Jain R, Robertson PL, Gandhi D et-al. Radiation-induced cavernomas of the brain. AJNR Am J Neuroradiol. 2005;26 (5): 1158-62. AJNR Am J Neuroradiol))


The definition of familial multiple cavernous malformation syndrome is when there is one or more of the following
((Rosário Marques I, Antunes F, Ferreira N, Grunho M. Familial cerebral cavernous malformation: Report of a novel [[KRIT1]] mutation in a Portuguese family. (2017) Seizure. 53: 72-74. doi:10.1016/j.seizure.2017.10.020))
((Mespreuve M, Vanhoenacker F, Lemmerling M. Familial Multiple Cavernous Malformation Syndrome: MR Features in This Uncommon but Silent Threat. (2016) Journal of the Belgian Society of Radiology. 100 (1): 51. doi:10.5334/jbr-btr.938))

multiple cerebral cavernous malformations

five or more cavernomas, or...

one cavernoma and at least one other family member with one or more cavernomas

mutations in one of the three genes, [[KRIT1]], [[CCM2]] or [[PDCD10]], which are associated with this disease

See: [[Zabramski classification of cerebral cavernomas]].

===== Radiographic features =====

The radiographic appearance of each cavernous malformation depends on size although in many instances individuals have innumerable lesions randomly distributed throughout the brain. 

For a discussion of the radiographic appearances see: cavernous malformations.
Differential diagnosis

The differential is that of other causes of cerebral microhemorrhages, including
((Jain R, Robertson PL, Gandhi D et-al. Radiation-induced cavernomas of the brain. AJNR Am J Neuroradiol. 2005;26 (5): 1158-62. AJNR Am J Neuroradiol))

cerebral amyloid angiopathy: usually numerous small foci

chronic hypertensive encephalopathy: more common in the basal ganglia

diffuse axonal injury (DAI)

cerebral vasculitis

radiation vasculopathy

hemorrhagic metastases

Parry-Romberg syndrome 
((Jain R, Robertson PL, Gandhi D et-al. Radiation-induced cavernomas of the brain. AJNR Am J Neuroradiol. 2005;26 (5): 1158-62. AJNR Am J Neuroradiol))

MRI appearance may be mimicked by:

artificial heart valve metallic emboli (very rare)

pneumocephalus (very rare) 
((Palma JA, Zubieta JL, Dominguez PD et-al. Pneumocephalus mimicking cerebral cavernous malformations in MR susceptibility-weighted imaging. AJNR Am J Neuroradiol. 2009;30 (6): e83. doi:10.3174/ajnr.A1549))