Diagnosed in the Autoimmune Neurology Clinic: Two patients with different phenotypes of spinocerebellar ataxia type 27 (P10-5.014)

Abstract

<h3>Objective:</h3> To describe two cases of spinocerebellar ataxia type 27 (SCA27), with a focus on the importance of differentiating episodic manifestations of neurogenetic conditions from inflammatory/autoimmune neurologic conditions. We emphasize the importance of obtaining an objective evaluation of the response to immunomodulatory treatment trials, and the significance of attaining a comprehensive family history. <h3>Background:</h3> SCA27 is an autosomal dominant condition caused by a pathogenic mutation in the fibroblast growth factor 14 (FGF14) gene located on chromosome 13. Phenotypic expression can vary in patients with the same genetic abnormality, often delaying diagnosis, especially in probands without affected relatives and/or with unremarkable or unavailable family history at the time of presentation. <h3>Design/Methods:</h3> We describe two patients referred to the Autoimmune Neurology clinic at the University of Utah for suspicion of an autoimmune/autoinflammatory disease, ultimately diagnosed with SCA27 as part of an expanded clinical evaluation. <h3>Results:</h3> A 68-year-old male patient (Case 1) presented with episodic dysarthria, dizziness, imbalance, and encephalopathy, with suspicion of a possible autoimmune etiology at the time of referral. At his first presentation, the patient reported no significant family history. Four years later, on revisiting the family history, he noted that his 49-year-old niece (Case 2) had also developed neurologic symptoms of unclear etiology. On evaluation, his niece was noted to have a tremor and ataxia. Both patients had evidence of systemic autoimmunity that likely contributed to suspicion of neurologic autoimmunity, and neither had age-advanced cerebellar or brainstem volume loss on imaging. Ultimately, genetic testing of both patients revealed a pathogenic mutation in the FGF14 gene consistent with SCA27. <h3>Conclusions:</h3> These two cases highlight the importance of a detailed interval family history at each visit, especially in undiagnosed adult patients. The presumptive autoinflammatory diagnosis in both patients reinforces the importance of comprehensive follow-up, including an objective analysis of response to any immunomodulatory diagnostic treatment trials. <b>Disclosure:</b> Dr. Hoshina has nothing to disclose. Dr. Wright has nothing to disclose. Dr. Warner has received intellectual property interests from a discovery or technology relating to health care. Dr. Richards has nothing to disclose. Karen Salzman has received publishing royalties from a publication relating to health care. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as a Consultant for venrock. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Leverna. Dr. Pulst 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 AAN. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Leninthal LLC. The institution of Dr. Pulst has received research support from NINDS. Dr. Pulst has received intellectual property interests from a discovery or technology relating to health care. Ms. Spoth has stock in Applied Genetic Technologies Corporation. Ms. Spoth has stock in MeiraGTx Holdings. Ms. Spoth has stock in Ocugen. Ms. Spoth has stock in PTC Therapeutics. 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 $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 Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. 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 and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.