Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype

Abstract

Background and purpose: CCMs are commonly associated with DVAs, but the incidence of association in familial CCM is unknown. The presence of a DVA significantly complicates surgical management of a CCM because of the risk of compromised venous drainage. In this investigation, we compared the incidence of a DVA in the presence of a CCM in sporadic and familial CCM cases comprising predominantly familial CCM with the Southwestern US common Hispanic mutation (or Q455X mutation) of CCM1.

Materials and methods: Retrospective review was performed of 112 patients identified with CCM. MR imaging review included the presence or absence of a DVA and number, location, size, and signal-intensity characteristics of CCMs. Record review included patient and family history and documented genetic mutations. Statistical analysis was performed by using the Fisher exact and 2-sample t tests.

Results: Eighty-one cases were familial, 18 were sporadic, and 13 were indeterminate. There were a total of 2212 CCMs: 2176, 21, and 15 in the familial, sporadic, and indeterminate groups, respectively. There was a close association of CCM and DVA (an apparent combined vascular lesion) in 8 of 18 (44%) sporadic cases and only 1 possible such association in the familial cases. The difference was highly statistically significant (P < .0001).

Conclusions: Familial CCMs are unlikely to be associated with DVAs, and sporadic CCMs have a high rate of association with DVA. This difference in imaging features of familial and sporadic CCMs suggests the possibility of a different developmental mechanism.

Fig 1.

Sporadic CCM with a very large DVA. A, Axial T2 SE of a 26-year-old woman shows a CCM near the left lateral ventricle. B, Postgadolinium T1 shows a large DVA involving much of the left frontal lobe. C and D, SWI demonstrates very clearly the CCM and DVA without gadolinium administration.

Fig 2.

DVA with a sporadic CCM, which enlarged with time. A, Initial T2 SE of a 14-year-old boy shows only a small subtle focus of low signal intensity. B, Repeat MR imaging 2 years later shows a more typical reticulated or popcorn-like appearance of a CCM. C, The associated DVA is best seen at a slightly lower level (T1 postgadolinium). D and E, The DVA and CCM are clearly demonstrated on SWI on the second study.