Spinocerebellar ataxia 21 and phenotypic variability within a single family (P9-11.004)

Abstract

<h3>Objective:</h3> We describe four patients within a family who presented to our movement disorders centers for evaluation of unsteady gait, tremor, and cognitive impairment found to have the same pathogenic variant in TMEM240. We describe their clinical courses and response to treatments to include posterior subthalamic area deep brain stimulation (PSA DBS) and provide accompanying video. <h3>Background:</h3> Spinocerebellar ataxia 21 (SCA21) is a rare cause of autosomal dominant ataxia with few patients (~50) published. It is an early-onset, slowly progressive cerebellar ataxia and may also have tremor, parkinsonism, oculomotor abnormalities, cognitive impairment, and psychiatric conditions. Given its rarity, the neurodevelopmental phenotype has not been well defined and phenotypic variability within the same variant has not yet described. <h3>Design/Methods:</h3> The index case, 12 year-old girl, presented with mild intellectual disability, severe action tremor since infancy, oculomotor abnormalities, anxiety, and depression. The full brother was noted to have mild action tremor since early childhood, speech delay and growth delay. The paternal half-brother presented with progressively worsening action tremor since early childhood which became impairing in adolescence as well as similar oculomotor abnormalities, learning disabilities, ADHD, and OCD. The father of the patients had onset of mild non-progressive action tremor of the hands since age 8, progressive ataxia, mild parkinsonism, mild intellectual disability and new onset progressive memory impairment. All patients were found to have the same pathogenic variant in TMEM240 (c.196G&gt;A p.G66R)). <h3>Results:</h3> The index patient tried numerous oral medications as well as botulinum neurotoxin (BoNT) injections without improvement. She underwent PSA DBS with marked improvement in tremor. Tremor in the paternal half-brother responded well to BoNT injections. The father underwent treatment for parkinsonism with carbidopa-levodopa and was started on rivastigmine without improvement. <h3>Conclusions:</h3> SCA21 is a slowly progressive autosomal dominant spinocerebellar ataxia with variable neurodevelopmental phenotypes including multiple movement disorders within the same variant. <b>Disclosure:</b> Dr. Hull has received publishing royalties from a publication relating to health care. Dr. Parnes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. Dr. Parnes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. The institution of Dr. Parnes has received research support from NIH. The institution of Dr. Parnes has received research support from Alexion. Dr. Jankovic has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Jankovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Revance, Allergan. The institution of Dr. Jankovic has received research support from Baylor College of Medicine. Dr. Jankovic has received research support from Abbvie. The institution of Dr. Jankovic has received research support from Abbvie.