Clinical and genetic spectrum of SCN2A-associated episodic ataxia

N Schwarz, T Bast, E Gaily, G Golla, K M Gorman, L R Griffiths, A Hahn, J Hukin, M King, C Korff, M J Miranda, R S Møller, B Neubauer, R A Smith, T Smol, P Striano, B Stroud, M Vaccarezza, G Kluger, H LercheW Fazeli

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability. Few reports have recently described SCN2A-associated episodic ataxia (EA). Our study identifies its broader clinical and genetic spectrum, and describes pharmacological approaches.

RESULTS: We report 21 patients with SCN2A-associated EA, of which 9 are unpublished cases. The large majority of patients present with epileptic seizures (18/21, 86%), often starting within the first three months of life (12/18, 67%). In contrast, onset of episodic ataxia ranged from 10 months to 14 years of age. The frequency of EA episodes ranged from brief, daily events up to 1-2 episodes per year each lasting several weeks. Potential triggers include minor head traumas and sleep deprivation. Cognitive outcome is favorable in most patients with normal or mildly impaired cognitive development in 17/21 patients (81%). No clear genotype-phenotype correlations were identified in this cohort. However, two mutational hotspots were identified, i.e. 7/21 patients (33%) harbor the identical pathogenic variant p.A263V, whereas 5/21 (24%) carry pathogenic variants that affect the S4 segment and its cytoplasmic loop within the domain IV. In addition, we identified six novel pathogenic variants in SCN2A. While acetazolamide was previously reported as beneficial in SCN2A-associated EA in one case, our data show a conflicting response in 8 additional patients treated with acetazolamide: three of them profited from acetazolamide treatment, while 5/8 did not.

CONCLUSIONS: Our study describes the heterogeneous clinical spectrum of SCN2A-associated EA, identifies two mutational hotspots and shows positive effects of acetazolamide in about 50%.

Original languageEnglish
Pages (from-to)438-447
Number of pages10
JournalEuropean Journal of Paediatric Neurology
Issue number3
Publication statusPublished - May 2019


  • Acetazolamide/therapeutic use
  • Adult
  • Anticonvulsants/therapeutic use
  • Ataxia/drug therapy
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Male
  • Mutation
  • NAV1.2 Voltage-Gated Sodium Channel/genetics


Dive into the research topics of 'Clinical and genetic spectrum of SCN2A-associated episodic ataxia'. Together they form a unique fingerprint.

Cite this