The Genetic Basis and Molecular Diagnosis of Vascular Tumors and Developmental Malformations

Abstract

Vascular anomalies, although largely benign, can be clinically devastating and affect an astounding 5–10 % of children worldwide, many with lifelong affliction. Vascular anomalies fall into two main groups: (1) vascular tumors that are intrinsically proliferative and (2) vascular malformations that represent true errors in development of the embryonic vasculature. Diagnosis of vascular malformations and tumors can be challenging, because of overlapping histological and clinical features and poorly understood pathogenesis. Accurate diagnosis is essential for family planning and disease management and better targeted therapies. The recognition of genetic vascular disorders and molecular testing has provided better clarification of the classifications and a more precise diagnosis. Unfortunately, the etiology of many vascular anomalies remains unknown, and diagnosis is challenging even in the most knowledgeable multidisciplinary centers managing these patients. Molecular genetic testing offers almost immediate promise for accurate diagnosis. Mutations in specific genes have been identified in familial examples and more recently in some sporadic occurring examples. Although still largely unavailable commercially, molecular genetic testing is available for certain vascular anomalies (mostly on a research basis only) to aid the physician in diagnosis and treatment of the child. In this chapter, we strive to provide the most up-to-date information regarding gene mutations associated with vascular anomalies and molecular genetic testing currently available for diagnosis. It is recognized that clinical evaluation and histologic analysis play a large role in the accurate diagnosis of vascular anomalies; however, these topics are minimally addressed in this review.