Genetics of vascular anomalies

• Published in: Seminars in pediatric surgery 2020-10, Vol.29 (5), p.150967-150967, Article 150967
• Main Authors: Nguyen, Ha-Long, Boon, Laurence M., Vikkula, Miikka
• Format: Article
• Language: English
• ISSN: 1055-8586; 1532-9453
• DOI: 10.1016/j.sempedsurg.2020.150967

Vascular anomalies are developmental defects of the vasculature and encompass a variety of disorders. The identification of genes mutated in the different malformations provides insight into the etiopathogenic mechanisms and the specific roles the associated proteins play in vascular development and maintenance. A few familial forms of vascular anomalies exist, but most cases occur sporadically. It is becoming evident that somatic mosaicism plays a major role in the formation of vascular lesions. The use of Next Generating Sequencing for high throughput and “deep” screening of both blood and lesional DNA and RNA has been instrumental in detecting such low frequency somatic changes. The number of novel causative mutations identified for many vascular anomalies has soared within a 10-year period. The discovery of such genes aided in unraveling a holistic overview of the pathogenic mechanisms, by which in vitro and in vivo models could be generated, and opening the doors to development of more effective treatments that do not address just symptoms. Moreover, as many mutations and the implicated signaling pathways are shared with cancers, current oncological therapies could potentially be repurposed for the treatment of vascular anomalies.