Universität zu Köln

Schwarz, N., Bast, T., Gaily, E., Golla, G., Gorman, K. M., Griffiths, L. R., Hahn, A., Hukin, J., King, M., Korff, C., Miranda, M. J., Moller, R. S., Neubauer, B., Smith, R. A., Smol, T., Striano, P., Stroud, B., Vaccarezza, M., Kluger, G., Lerche, H. and Fazeli, W. (2019). Clinical and genetic spectrum of SCN2A-associated episodic ataxia. Eur. J. Paediatr. Neurol., 23 (3). S. 438 - 448. OXFORD: ELSEVIER SCI LTD. ISSN 1532-2130

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Abstract

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 Results: We report 21 patients with SCN2A-associated EA, of which 9 are unpublished cases.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%. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schwarz, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bast, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaily, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Golla, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gorman, K. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Griffiths, L. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahn, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hukin, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED King, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Korff, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Miranda, M. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moller, R. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neubauer, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smith, R. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smol, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Striano, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stroud, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vaccarezza, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kluger, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lerche, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fazeli, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-148889
DOI:	10.1016/j.ejpn.2019.03.001
Journal or Publication Title:	Eur. J. Paediatr. Neurol.
Volume:	23
Number:	3
Page Range:	S. 438 - 448
Date:	2019
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1532-2130
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEONATAL EPILEPSY; CHANNEL GENE; SCN2A; MUTATIONS; ENCEPHALOPATHY; VARIANTS; SEIZURES Multiple languages Clinical Neurology; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14888