The adverse health and economic impacts of pediatric arterial ischemic stroke are increasingly appreciated. Mechanisms underlying childhood arterial ischemic stroke (AIS) are heterogeneous and poorly understood but critical for the development of targeted interventions. Cerebral vasculopathies are one of the major causes of pediatric stroke. Genetic discoveries are being increasingly recognized as an important cause of many cerebral vasculopathies. This symposium will highlight the role of advanced genetic analysis in pediatric cerebrovascular diseases, focusing on the common and currently known genes and molecular pathways involved in genetic cerebral vasculopathies. The role of vascular smooth muscle cell dysfunction will be highlighted, as well as the role of endothelial cell dysfunction in small vessel diseases. Current approaches for the genetic evaluation and its implementation in pediatric stroke based on a clinical and radiologicaldriven approach will be discussed, using a pattern-recognition approach. Existing challenges in the provision of accurate definition and phenotyping of patients with vasculopathies in order to facilitate future genotype– phenotype correlations and identify novel associations and disease mechanisms will be highlighted along with potential ways for enhancing gene discoveries in this developing field. Learning Objectives
- Identify specific clinical as well as radiological phenotypes associated with common and newly described monogenic disorders related to pediatric stroke.
- Understand the basic concepts of cellular and molecular pathways involved in genetic medium to large cerebral stenoocclusive arteriopathies and small vessel diseases. Impact Statements
- Identify clinical and radiological patterns of recently discovered genetic cerebral vasculopathies including arteriopathies and small – vessel diseases.
- Understand the basic pathophysiological concepts involved in pediatric cerebral vasculopathies.
Moran Hausman-Kedem, MD
Pediatric Neurology Institute, Dana-Dwek Children’s Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
A Pattern-recognition Approach to Genetic Arteriopathies
Nomazulu Dlamini, MBBS, MRCPCH, MSc (Lon), PhD
The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
Converging Molecular Mechanisms of Genetic Cerebral Vasculopathies
Vijeya Ganesan MD
UCL Great Ormond Street Institute of Child Health, London, UK
Molecular Basis of Cerebral Small Vessel Vasculopathies and Microvascular Dysfunction
Patricia L. Musolino, MD, PhD
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA