Intrafamilial Heterogeneity in Spinocerebellar Ataxia Type 21 (P8-11.015)

Abstract

<h3>Objective:</h3> To emphasize the variability of clinical presentations of genetic movement disorders as depicted by a family with SCA21. <h3>Background:</h3> Spinocerebellar ataxia type 21 (SCA21) is a rare autosomal dominant condition that can have a variety of motor, cognitive, or behavioral manifestations. This clinical variability is seen both between and within families with the same mutation. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 51-year-old woman presented to clinic for evaluation of lifelong worsening balance impairment and hand clumsiness. Her physical exam noted marked ataxia and dysmetria in the extremities, ataxic gait, and spastic extremities, and neuropsychiatric testing was remarkable for mild impairments. Following further workup, a family history of neurologic complaints was taken, which revealed that one of her three children had tremors. When brought to clinic, the patient’s daughter revealed a lifelong history of bilateral hand tremors with worsening over the previous two years. She further noted a slowness in her thinking that required special education courses, as well as other mild motor difficulties. Given the potential for a genetic condition, an ataxia panel was ordered, which revealed a c.509C&gt;Tp.P170L mutation in the TMEM240 gene in the patient and her daughter. <h3>Conclusions:</h3> This case emphasizes the importance of recognizing intrafamilial clinical heterogeneity in the diagnosis of genetic movement disorders. It highlights the potential benefits of an investigation into a family history notable for neurological disorders, which may provide the opportunity for appropriate testing and diagnosis. The variable presentations of spinocerebellar ataxias within families have been explored in a limited number of case reports. The identification of a possible unknown factor driving these differences in presentation could have potential therapeutic implications. While all reported cases of SCA21 have some degree of gait and limb ataxia, only one case has reported tremor onset followed by ataxia and dystonia, as seen in this case. <b>Disclosure:</b> Emma *Use 368242 Wetmore has nothing to disclose. Dr. Decker has nothing to disclose. Maysen Mesaros has nothing to disclose. An immediate family member of Dr. Rodriguez-Porcel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anmeal. Dr. Rodriguez-Porcel has received publishing royalties from a publication relating to health care.