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Medientyp: E-Artikel Titel: Huntington's Disease with Small CAG Repeat Expansions Beteiligte: Heinzmann, Anna; Sayah, Sabrina; Lejeune, François‐Xavier; Hahn, Valérie; Teichmann, Marc; Monin, Marie‐Lorraine; Marchionni, Enrica; Gérard, Fleur; Charles, Perrine; Pariente, Jérémie; Durr, Alexandra Erschienen: Wiley, 2023 Erschienen in: Movement Disorders Sprache: Englisch DOI: 10.1002/mds.29427 ISSN: 0885-3185; 1531-8257 Schlagwörter: Neurology (clinical) ; Neurology Entstehung: Anmerkungen: Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Carriers of small cytosine‐adenine‐guanine (CAG) repeats below 39 in the <jats:italic>HTT</jats:italic> gene are traditionally associated with milder Huntington's disease, but their clinical profile has not been extensively studied.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To study the phenotype of CAG<jats:sub>36‐38</jats:sub> repeat carriers.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We included 35 patients and premanifest carriers of CAG<jats:sub>36‐38</jats:sub> repeats. We compared clinical and neuropsychological profiles of 11 CAG<jats:sub>36‐38</jats:sub> patients with 11 matched CAG<jats:sub>40‐42</jats:sub> patients. In addition, we analyzed 243 CAG<jats:sub>36‐38</jats:sub> individuals from the ENROLL study to complete the phenotype description.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Global cognitive efficiency and performance in different cognitive subdomains were similar in small CAG<jats:sub>36‐38</jats:sub> and typically CAG<jats:sub>40‐42</jats:sub> expanded individuals. Chorea as the first symptom was significantly less frequent for CAG<jats:sub>36‐38</jats:sub> patients (<jats:italic>P</jats:italic> = 0.04) despite similar total motor scores at first visit. Total motor score at last visit was significantly lower in CAG<jats:sub>36‐38</jats:sub> carriers (<jats:italic>P</jats:italic> = 0.003). The similar cognitive and different motor profile of CAG<jats:sub>36‐38</jats:sub> (n = 243) and CAG<jats:sub>40‐42</jats:sub> (n = 4675) carriers was confirmed in the ENROLL database. Additionally, clinicians were significantly less confident in diagnosing Huntington's disease (<jats:italic>P</jats:italic> = 2.4e−8) and diagnosis happened significantly later in CAG<jats:sub>36‐38</jats:sub> (<jats:italic>P</jats:italic> = 2.2e−6) despite a similar age at symptom onset (<jats:italic>P</jats:italic> = 0.29).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>We showed that small CAG<jats:sub>36‐38</jats:sub> expansion carriers had a similar cognitive profile to those with the more common CAG<jats:sub>40‐42</jats:sub> expansions. These individuals may evade molecular diagnosis because of the absence of chorea rather than because of a low penetrance of symptoms. This finding should encourage neurologists to consider Huntington's disease in cognitively impaired elderly patients without typical chorea and anticipate consequences for genetic counseling in their offspring. © 2023 The Authors. <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</jats:p></jats:sec>