Table 9.

TEK-Related Venous Malformations: Molecular Pathogenesis

PhenotypeTypes of genetic variants
VMCM Germline (inherited) pathogenic TEK variant in addition to a somatic (mosaic) pathogenic variant 1, 2
MSVM Double pathogenic variants. 3 Affected persons typically acquire an initial mosaic activating pathogenic TEK variant & subsequently acquire a second mosaic activating pathogenic variant (or a "second hit”). The second pathogenic variant may vary among lesions from the same person.
Unifocal VM In ~60% of affected persons, isolated VM are caused by a somatic pathogenic variant in TEK. 2
BRBN syndrome Unlike VMCM-causing pathogenic variants, BRBN syndrome-causing pathogenic variants typically occur on the same allele (i.e., double [cis] pathogenic variants [>83%]). The same double (cis) pathogenic variants are seen in multiple lesions from the same person, suggesting a common cellular ancestor for the lesion. 3

BRBN = blue rubber bleb nevus; MSVM = multifocal sporadic venous malformations; VM = venous malformation; VMCM = multiple cutaneous and mucosal venous malformations

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From: TEK-Related Venous Malformations

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