Table 1.

Comparison of the Similar and Dissimilar Features of the HHT and CCM Pathologies

FeatureHHTCCM
Prevalence1.25–2.0 per 10 000101,121Familial, <5 per 10 000122; sporadic, 1 per 200122,123
Organs affectedLung, brain, gastrointestinal tract, liver, skin, and oronasal cavity4,103Retina, brain, skin, and liver122
Vascular bed of originArterioles (Eng EC-iKO),76,90 venous enlargement (Alk1 EC-KO, Eng EC-KO),56,83 loss of arterial identity (Alk1 EC-KO)56,76Venous5,7,124
Type of malformationTelangiectasies, arteriovenous malformations103Single and multilumen cavernomas (mulberry lesions)125
Increased permeability, vessel fragilityYes64Yes125
Pericyte coverageReduced76,84,110Reduced125
Associated genes mutated in ECsALK1,109 ENDOGLIN,108 BMP9,113 SMAD4.117 Haplo-insufficiency plus response to injury in adult in mice85CCM1, CCM2, CCM3.122,126Local homozygous loss-of-function mutation (local loss of heterozygosity for familial CCM)102,127129
Mosaicism of mutation in ECs of the lesionYes76,130Yes129
Deregulated TGF-β/BMP signalingReduced (primary target)95Increased (secondary target)57
Junction dismantlingNot describedYes57,125,132
Proliferative statusIncreased83,101Increased5
SproutingYes26,27,133Not described
EndMTDescribed only for Eng heterozygous and Eng EC-KO in tumors35Yes58,134
  • Data in the Table refer primarily to human pathology unless differently specified. BMP indicates bone morphogenetic protein; CCM, cerebral cavernous malformation; EC, endothelial cell; EndMT, endothelial-to-mesenchymal transition; HHT, hereditary hemorrhagic telangiectasia; KO, knockout; and TGF-β, transforming growth factor-β.