Fragile-X-associated Tremor/Ataxia Syndrome in a Woman with Full Mutation: A Case Report (P5-11.009)

Abstract

<h3>Objective:</h3> To describe the first case of FXTAS in a full mutation woman without Fragile X syndrome. <h3>Background:</h3> Fragile-X-associated tremor/ataxia syndrome (FXTAS) is caused by expanded trinucleotide (CGG) repeats between 55–199 (premutation) in the <i>Fragile X Mental Retardation 1 (FMR1) gene</i>. Core clinical features of FXTAS include cerebellar ataxia, intention tremor and Parkinsonism. In contrast, a full mutation of CGG repeats&gt;200 repeats with methylation of the gene leads to fragile X syndrome, which is characterized by early intellectual disability, autistic features, and seizures. <i>FMR1</i> premutation carrier women presenting as FXTAS have been reported. This is the first report of a woman with a full mutation presenting with FXTAS. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 65-year-old woman presented with problems with dexterity and shuffling gait. The patient also complained of urinary urgency, constipation, anxiety, depression, and mild cognitive complaints. The patient’s son was diagnosed with fragile X syndrome at 14 months. Neurological exam of the patient showed parkinsonism, action tremor and limb ataxia. MRI brain demonstrated chronic ischemic small vessel disease and mildly reduced brain volume. <i>FMR1 CGG</i> repeat sizes were 20 and &gt;200. The 20 repeat allele was seen on the active X chromosome (representing non-random X-inactivation), while the &gt;200 repeat allele was fully methylated on Southern blot. Testing for Parkinson’s disease-associated genes were negative. <h3>Conclusions:</h3> This is the first report of a woman with a <i>FMR1</i> full mutation presenting with signs and symptoms of FXTAS. Several cases of FXTAS have been reported in <i>FMR1</i> full mutation men with fragile X syndrome due to mosaicism of repeat sizes and the presence of a premutation allele. Full mutation adults with complete methylation have not been reported to have FXTAS. The clinical presentation of this case might be due to size or methylation mosaicism in brain. Alternatively, one could also consider a different disease mimicking FXTAS. <b>Disclosure:</b> Dr. Kazanci has nothing to disclose. The institution of Dr. Berry-Kravis has received research support from NIH. The institution of Dr. Berry-Kravis has received research support from Ovid. The institution of Dr. Berry-Kravis has received research support from Zynerba. The institution of Dr. Berry-Kravis has received research support from Roche. The institution of Dr. Berry-Kravis has received research support from CDC. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. The institution of Dr. Berry-Kravis has received research support from GeneTx. The institution of Dr. Berry-Kravis has received research support from Angelman Syndrome Foundation. The institution of Dr. Berry-Kravis has received research support from Acadia. The institution of Dr. Berry-Kravis has received research support from GW. The institution of Dr. Berry-Kravis has received research support from Anavex. The institution of Dr. Berry-Kravis has received research support from Rett Syndrome Research Trust. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Mallinckrodt. The institution of Dr. Berry-Kravis has received research support from Together Strong Foundation. The institution of Dr. Berry-Kravis has received research support from Orphazyme. The institution of Dr. Berry-Kravis has received research support from Ionis. The institution of Dr. Berry-Kravis has received research support from Taysha. The institution of Dr. Berry-Kravis has received research support from Erydel. The institution of Dr. Berry-Kravis has received research support from Tetra. The institution of Dr. Berry-Kravis has received research support from Neuren. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. Dr. Hall 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 American Academy of Neurology. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier - Parkinsonism and Related Disorders. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Hall has received research support from Parkinson’s Foundation. The institution of Dr. Hall has received research support from CHDI. The institution of Dr. Hall has received research support from Biohaven. The institution of Dr. Hall has received research support from Neurocrine. The institution of Dr. Hall has received research support from Uniqure. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as a Study section with NIH.