Abstract Details

Title The Neurodevelopmental and Motor Phenotype of SCA21 (ATX-TMEM240)

Topic Child Neurology and Developmental Neurology

Presentation(s) P14 - Poster Session 14 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-002

Objective NA

Background Spinocerebellar ataxia type 21 (SCA21) is a rare form of cerebellar ataxia that commonly presents with motor, cognitive, and behavioral impairments. Although these features have been identified as part of the clinical manifestations of SCA21, the neurodevelopmental disorders associated with SCA21 have not been well studied or described.

Design/Methods Three SCA21 subjects underwent genetic, cognitive, behavioral, adaptive function, and motor standardized and quantitative assessments.

Results Genetic work-up demonstrated the c.196 G>A (p.Gly66Arg) variant, which is the second recurrent mutation associated with SCA21. Cognitive evaluation resulted in full-scale IQ scores in the <0.1-1 percentile range, consistent with the subjects’ diagnoses of Intellectual Disability. Adaptive function was significantly impaired with adaptive behavior composite scores in the <1-5 percentile range. Social communication impairments were demonstrated, with two of the subjects having diagnoses of Autism Spectrum Disorder, which has never been described in SCA21. Motor difficulties were observed across manual dexterity, aiming/catching, and balance domains with scores in the 0.1-9 percentile range. Quantitative gait analysis showed markedly abnormal spatiotemporal gait variables including decreased velocity, cadence, and step length as well as increased stride width and gait variability index, indicative of poor gait control and cerebellar dysfunction. Clinical evaluation also highlighted a striking variability in clinical symptoms, with greater ataxia correlating with greater severity of neurodevelopmental disorder diagnoses. Notably, neurodevelopmental outcomes have improved with intervention over time.

Conclusions This case series identifies that neurodevelopmental disorders are a key feature of SCA21 and may precede the presence of motor abnormalities. Furthermore, the coexistence of ataxia and neurodevelopmental disorders in these subjects suggests a role for spinocerebellar pathways in both outcomes. The findings in this study highlight the importance of evaluation of neurodevelopmental concerns in the context of progressive motor abnormalities as well as the need for timely intervention to ultimately improve quality of life for individuals with SCA21.

Authors/Disclosures
Emma Burdekin PRESENTER	No disclosure on file
Brent L. Fogel, MD, PhD, F�鶹��ýӳ�� (UCLA Neurology)	Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for National Ataxia Foundation. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Ataxia Global Initiative. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Today. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genes. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neuromarkers. The institution of Dr. Fogel has received research support from the National Institutes of Health. The institution of Dr. Fogel has received research support from the National Ataxia Foundation. The institution of an immediate family member of Dr. Fogel has received research support from the National Institutes of Health, the National Science Foundation, and the Department of Defense. The institution of Dr. Fogel has received research support from US Department of Defense .
Shafali Jeste, MD, F�鶹��ýӳ�� (Children's Hospital of Los Angeles)	Dr. Jeste has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for �鶹��ýӳ�� Continuum. The institution of Dr. Jeste has received research support from NIH. The institution of Dr. Jeste has received research support from DoD. The institution of Dr. Jeste has received research support from Dup15q Alliance.
Julian Martinez Agosto, MD, PhD (University of California Los Angeles)	Julian Martinez Agosto, MD, PhD has nothing to disclose.
Jessica E. Rexach, MD, PhD (UCLA Medical Center)	Dr. Rexach has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Rujuta B. Wilson, MD (David Geffen School of Medicine At UCLA)	Dr. Wilson has nothing to disclose.

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