Abstract Details

Title Channelopathies are a frequent cause of genetic ataxias associated with cerebellar atrophy

Topic Movement Disorders

Presentation(s) P7 - Poster Session 7 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-007

Objective To examine the spectrum of genetic ataxias associated with cerebellar atrophy in a Canadian cohort, and the diagnostic yield of whole exome sequencing (WES) for this group of conditions.

Background Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a clinically and genetically heterogeneous group of conditions, making the approach to diagnosis challenging.

Design/Methods 93 participants from 67 families with cerebellar atrophy were recruited for this multicenter prospective cohort study. WES was performed for all participants between 2011 and 2017 as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare).

Results

A genetic diagnosis was established in 54% of families (36/67). Pathogenic variants were found in 22 known genes, providing a diagnosis for 32/36 families (89%), and in four novel genes, accounting for 4/36 families (11%). 31/67 families (46%) remained without a genetic diagnosis. The most common diagnoses were channelopathies in 9/36 families (25%). Otherwise, inheritance was autosomal recessive in the majority of conditions. Additional clinical findings provided useful clues to specific diagnoses.

Conclusions We report on the high frequency of channelopathies as a cause of genetic ataxias associated with cerebellar atrophy and the utility of WES for this group of conditions.

Authors/Disclosures
Laurence Gauquelin, MD PRESENTER	No disclosure on file
	No disclosure on file
Mark Tarnopolsky, MD, PhD, FRCP (McMaster University)	Dr. Tarnopolsky has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Tarnopolsky has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Reneo. Dr. Tarnopolsky has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Tarnopolsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reneo . Dr. Tarnopolsky has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Dr. Tarnopolsky has stock in Synaptive Medical. Dr. Tarnopolsky has stock in CloudDx. The institution of Dr. Tarnopolsky has received research support from Canadian Institute for Health Research. Dr. Tarnopolsky has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Bernard Brais, MD (Montreal Neurological Institute-Hospital)	Dr. Brais has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Francois Bernier, PhD (Eisai)	No disclosure on file
	No disclosure on file
Guy A. Rouleau, MD, PhD, FAAN (Montreal Neurological Institute and Hospital)	Dr. Rouleau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NovoNordisk. Dr. Rouleau has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for AL-S Pharma.
Oksana Suchowersky, MD, FAAN (University of Alberta Hospital)	Dr. Suchowersky has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos/Alexion. The institution of Dr. Suchowersky has received research support from Roche. The institution of Dr. Suchowersky has received research support from Wave LifeSciences. The institution of Dr. Suchowersky has received research support from CHDI. Dr. Suchowersky has received publishing royalties from a publication relating to health care. Dr. Suchowersky has received publishing royalties from a publication relating to health care.
Kym Boycott	No disclosure on file
Grace Yoon, MD	Dr. Yoon has nothing to disclose.

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