Abstract Details

Title A Familial Analysis of Stiff-Person Spectrum Disorder utilizing the Utah Population Database

Topic Autoimmune Neurology

Presentation(s) S40 - Autoimmune Neurology: Stiff Person Syndrome/GAD65 Neurological Autoimmunity, CIDP, and MOGAD (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Background There is limited understanding of the pathophysiology of SPSD. The common co-occurrence of autoimmune diseases in these patients suggests a shared genetic predisposition.

Objective To describe the clinical and immunologic findings of a large cohort of patients with
stiff-person spectrum disorder (SPSD) while exploring for potential familial clustering within the Utah Population Database (UPDB).

Design/Methods We performed a retrospective review of all confirmed SPSD patients diagnosed and managed in the Autoimmune Neurology Clinic at the University of Utah. Using the UPDB, a population-based genealogic resource containing medical and demographic information of over 11 million individuals, we identified high-risk pedigrees with excess familial aggregation of SPSD using the Familial Standardized Incidence Ratio (FSIR). Unaffected subjects were identified and matched 10:1 to SPSD patients by age, birth year, and pedigree structure in the UPDB. Familial risk analyses were performed to estimate the heritability of SPSD separately using multivariate logistic regression adjusting for sex, birth year, race, and ethnicity.

Results We identified a total of 46 patients with a SPSD. The median age was 52 years old (SD 14 years), and 78% were female and 93% self-identified as White. A total of 22 (47%) had classical SPS, 16 (34%) had SPS with an overlapping with ataxia, epilepsy, or encephalitis. The majority (95%) had glutamic acid decarboxylase (GAD65) antibodies, 11 (24%) had α1-subunit of the glycine receptor (GlyR) antibodies (8 with concomitant GAD65 antibodies), and one patient tested negative for all antibodies. Twenty-eight patients had a comorbid autoimmune disorder with the most frequent being insulin-dependent diabetes (30%) and autoimmune thyroid disease (17%).

Conclusions SPSD is a complex group of disorders predominantly defined by GAD65 and GlyR antibodies. The co-occurrence of autoimmune diseases and potential familial clustering suggests that genetic, inherited factors may play a role in SPSD.

Authors/Disclosures
Justin Abbatemarco, MD (Cleveland Clinic Foundation) PRESENTER	Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics, Inc.. The institution of Dr. Abbatemarco has received research support from Horizon.
Paul D. Crane, MD (University of Colorado)	Dr. Crane has nothing to disclose.
Jonathan R. Galli, MD (University of Utah)	Dr. Galli has nothing to disclose.
Stefanie J. Rodenbeck, MD (Indiana University)	Dr. Rodenbeck has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Rodenbeck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Rodenbeck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen.
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Ka-Ho Wong (U of U Neurology Clinic)	The institution of Mr. Wong has received research support from The Sumaira Foundation . The institution of Mr. Wong has received research support from The Siegel Rare Neuroimmune Association.
John E. Greenlee, MD, FAAN (University of Utah)	Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Greenlee has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Zeigler Cohen Roche. Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Sommers Schwartz PC. Dr. Greenlee has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for St Francis Hospital. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Greenlee has received publishing royalties from a publication relating to health care.
Stacey Clardy, MD, PhD, FAAN (University of Utah)	Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca/Alexion. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen/Horizon. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from NIH/NINDS. The institution of Dr. Clardy has received research support from SRNA. The institution of Dr. Clardy has received research support from Alexion/AstraZeneca. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with U of Iowa, Miami, Stanford, Barrow, Beaumont Health, CCF, Emory, Penn State, Mayo Clinic, Walter Reed.