Abstract
One in 10 infants are born with a vascular birthmark each year. Some vascular birthmarks,
such as infantile hemangiomas, are common, while vascular malformations, such as capillary,
lymphatic, venous, and arteriovenous malformations, are less so. Diagnosing uncommon
vascular birthmarks can be challenging, given the phenotypic heterogeneity and overlap
among these lesions. Both sporadic and germline variants have been detected in various
genes associated with vascular birthmarks. Identification of these genetic variants
offers insight into both diagnosis and underlying molecular pathways and can be fundamental
in the discovery of novel therapeutic approaches. The PIK3/AKT/mTOR and RAS/MEK/ERK
signaling pathways, which mediate cell growth and angiogenesis, are activated secondary
to genetic variations in vascular malformations. Somatic variants in TEK (TIE2) and PIK3CA cause venous malformations. Variants in PIK3CA also cause lymphatic malformations as well as a number of overgrowth syndromes associated
with vascular anomalies. Variants in GNAQ and GNA11 have been identified in both so-called “congenital” hemangiomas and capillary malformations.
RASA1 and EPHB4 variants are associated with capillary malformation-arteriovenous malformation syndrome.
This review discusses the genetics of vascular birthmarks, including the various phenotypes,
genetic variants, pathogenesis, associated syndromes, and new diagnostic techniques.
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Article Info
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Published online: February 15, 2022
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