Abstract Details

Title Monogenic Causes of Cerebrovascular Disease in Childhood

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-057

Objective

To report a case series of children with cerebrovascular disease due to monogenic vasculopathies, and place each gene into a clinically useful classification scheme based on stroke subtype and imaging characteristics.

Background

Stroke is now recognized as an important cause of morbidity and mortality in children. The risk factors for childhood stroke are distinct from risk factors in older adults, and hereditary stroke disorders remain under-recognized. In young adults, genetic causes of cerebral vasculopathy account for up to 10% of cryptogenic strokes, but the incidence is unknown in children, and there have been limited reports on imaging phenotypes in children.

Design/Methods We performed a retrospective review of patients age 0 to 21 who presented to MGH from 2002-2018 with monogenic vasculopathies and vascular malformation, small or large vessel disease, transient ischemic attack, ischemic stroke, and/or hemorrhagic stroke. After review of neurological and systemic features, patients were classified according to imaging phenotype. Molecular mechanisms, treatment strategies, and clinical outcomes are discussed.

Results We classified each patient into one of three categories of cerebrovascular disease according to the predominant imaging features: small vessel disease, large vessel disease, and vascular malformations. We describe additional imaging and clinical features in each patient. Small vessel disease was seen in patients with mutations in ACTA2, FOXC1, COL4A1, COL4A2, NOTCH3, TREX1 and CECR1. Among large vessel disease we found children with SAMDH1, GLA, ACTA2, JAG1, NOTCH2, NF1 and ABCC6 mutations. Finally, children presenting with vascular malformations had mutations in ENG, SMAD3, TGFBR1, TGFBR2 or KRIT1 genes.

Conclusions

We review over 20 pediatric patients seen in a single stroke center with monogenic vasculopathies. We provide a framework for classifying monogenic cerebrovascular disorders in children based on imaging phenotype and stroke subtype. This study provides important insight into stroke pathogenesis, and will assist in the recognition and diagnosis of monogenic vasculopathies in children.

Authors/Disclosures
Bridget L. Ostrem, MD, PhD (Massachusetts General Hospital) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Patricia Musolino, MD, PhD	An immediate family member of Dr. Musolino has received personal compensation for serving as an employee of EMD Sorono. Dr. Musolino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Minoryx Pharmaceuticals. Dr. Musolino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for IONIS Pharmaceuticals . Dr. Musolino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inozyme Pharma. Dr. Musolino has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex Pharmaceuticals. An immediate family member of Dr. Musolino has or had stock in 2seventy Bio. An immediate family member of Dr. Musolino has or had stock in Editas Medicine. An immediate family member of Dr. Musolino has or had stock in Generation Bio. An immediate family member of Dr. Musolino has or had stock in Beam Therapeutics. An immediate family member of Dr. Musolino has or had stock in Ebotec . An immediate family member of Dr. Musolino has or had stock in Novonordisk. An immediate family member of Dr. Musolino has or had stock in Morphosys. The institution of Dr. Musolino has received research support from National Institute of Health-NINDS-R01. The institution of Dr. Musolino has received research support from Angea Biotherapeutics. The institution of Dr. Musolino has received research support from Minoryx Pharmaceuticals. The institution of Dr. Musolino has received research support from Belanger Foundation. The institution of Dr. Musolino has received research support from Rozwat Family Foundation. The institution of Dr. Musolino has received research support from Dooley Family Foundation. Dr. Musolino has received intellectual property interests from a discovery or technology relating to health care. Dr. Musolino has received publishing royalties from a publication relating to health care.

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