We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study.
- Authors
Krenn, Martin; Sener, Merve; Rath, Jakob; Zulehner, Gudrun; Keritam, Omar; Wagner, Matias; Laccone, Franco; Iglseder, Stephan; Marte, Sonja; Baumgartner, Manuela; Eisenkölbl, Astrid; Liechtenstein, Christian; Rudnik, Sabine; Quasthoff, Stefan; Grinzinger, Susanne; Spenger, Johannes; Wortmann, Saskia B.; Löscher, Wolfgang N.; Zimprich, Fritz; Kellersmann, Anna
- Abstract
Background: Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects resulting in impaired neuromuscular transmission. Although effective treatments are available, CMS is probably underdiagnosed, and systematic clinico-genetic investigations are warranted. Methods: We used a nationwide approach to collect Austrian patients with genetically confirmed CMS. We provide a clinical and molecular characterization of this cohort and aimed to ascertain the current frequency of CMS in Austria. Results: Twenty-eight cases with genetically confirmed CMS were identified, corresponding to an overall prevalence of 3.1 per million (95% CI 2.0–4.3) in Austria. The most frequent genetic etiology was CHRNE (n = 13), accounting for 46.4% of the cohort. Within this subgroup, the variant c.1327del, p.(Glu443Lysfs*64) was detected in nine individuals. Moreover, causative variants were found in DOK7 (n = 4), RAPSN (n = 3), COLQ (n = 2), GMPPB (n = 2), CHAT (n = 1), COL13A1 (n = 1), MUSK (n = 1) and AGRN (n = 1). Clinical onset within the first year of life was reported in one half of the patients. Across all subtypes, the most common symptoms were ptosis (85.7%), lower limb (67.9%), upper limb (60.7%) and facial weakness (60.7%). The majority of patients (96.4%) received specific treatment, including acetylcholinesterase inhibitors in 20, adrenergic agonists in 11 and 3,4-diaminopyridine in nine patients. Conclusions: Our study presents the first systematic characterization of individuals with CMS in Austria, providing prevalence estimates and genotype–phenotype correlations that may help to improve the diagnostic approach and patient management.
- Subjects
AUSTRIA; CONGENITAL myasthenic syndromes; ADRENERGIC agonists; NEUROMUSCULAR transmission; BLEPHAROPTOSIS; GENETIC disorders; ACETYLCHOLINESTERASE inhibitors
- Publication
Journal of Neurology, 2023, Vol 270, Issue 2, p909
- ISSN
0340-5354
- Publication type
Article
- DOI
10.1007/s00415-022-11440-0