Myoclonus and Dystonia as Recurrent Presenting Features in Patients with the SCA21-Associated TMEM240 p.Pro170Leu Variant

Tremor Other Hyperkinet Mov (N Y). 2024 Apr 10:14:16. doi: 10.5334/tohm.858. eCollection 2024.

Abstract

Background: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240. A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease.

Case series: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes.

Discussion: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.

Keywords: Dystonia; Myoclonus; Pro170Leu; SCA21; Spinocerebellar ataxia; TMEM240.

Publication types

  • Review
  • Case Reports

MeSH terms

  • Ataxia
  • Dystonia* / diagnosis
  • Dystonia* / genetics
  • Dystonic Disorders*
  • Humans
  • Hyperkinesis
  • Membrane Proteins
  • Myoclonus* / diagnosis
  • Myoclonus* / genetics
  • Rare Diseases
  • Spinocerebellar Degenerations*
  • Syndrome

Substances

  • TMEM240 protein, human
  • Membrane Proteins

Supplementary concepts

  • Myoclonic dystonia
  • Spinocerebellar ataxia 21

Grants and funding

JW and MZ receive research support from the German Research Foundation (DFG 458949627; WI-1820/14-1; ZE 1213/2-1). MZ acknowledges grant support by the European Joint Programme on Rare Diseases (EJP RD Joint Transnational Call 2022), and the German Federal Ministry of Education and Research (BMBF, Bonn, Germany), awarded to the project PreDYT (PREdictive biomarkers in DYsTonia, 01GM2302), by the Federal Ministry of Education and Research (BMBF) and the Free State of Bavaria under the Excellence Strategy of the Federal Government and the Länder, as well as by the Technical University of Munich – Institute for Advanced Study. M.Z. is a member of the Medical and Scientific Advisory Council of the Dystonia Medical Research Foundation and a member of the Governance Council of the International Cerebral Palsy Genomics Consortium. MZ`s research is supported by a “Schlüsselprojekt” grant from the Else Kröner-Fresenius-Stiftung (2022_EKSE.185). RJ is supported by the National Institute for Neurological Research, Czech Republic, Programme EXCELES, ID Project No. LX22 NPO5107, funded by the European Union – Next Generation EU and also by the Charles University: Cooperation Program in Neuroscience. L.M.R. received research grant from the Italian Ministry of Health (GR-2009-1594645). B.G. received grant support by the Italian Ministry of Health (Ricerca Corrente) and by Fondazione Mariani (CM23).