Paroxysmal tonic upgaze: A heterogeneous clinical condition responsive to carbonic anhydrase inhibition.
Acetazolamide
CACNA1A
Episodic ataxia
Paroxysmal tonic upgaze
SIM1
Sultiame
Journal
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
ISSN: 1532-2130
Titre abrégé: Eur J Paediatr Neurol
Pays: England
ID NLM: 9715169
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
05
06
2019
revised:
15
10
2019
accepted:
09
11
2019
pubmed:
8
12
2019
medline:
1
9
2020
entrez:
8
12
2019
Statut:
ppublish
Résumé
Paroxysmal tonic upgaze (PTU), defined as an involuntary upward movement of the eyes, has been considered as a benign phenomenon but may also be associated with ataxia and developmental delay. We report eight children with PTU; six of them also exhibiting symptoms of ataxia and/or developmental delay. Treatment with carbonic anhydrase inhibition was offered to children with persisting and/or severe forms. Whole-exome sequencing and genome-wide array analysis (n = 7) did not reveal mutations in the three known genes associated with PTU (CACNA1A, GRID2, SEPSECS), whereas by MLPA a heterozygous deletion of exon 31 of the CACNA1A gene could be detected in one patient, her mother and two further family members. Further exome and array analysis showed no recurrent variants in potentially novel PTU-related genes in more than one patient. A de novo variant at a highly conserved position in the SIM1 gene was detected in one patient, for which a pathogenic effect could be speculated. Carbonic anhydrase inhibition was started in five children and proved at least partially effective in all of them. Irrespective of the clinical background and the molecular basic mechanism of PTU, therapeutic carbonic anhydrase inhibition was effective in all five children (acetazolamide, n = 3; sultiame, n = 2) who received this treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Paroxysmal tonic upgaze (PTU), defined as an involuntary upward movement of the eyes, has been considered as a benign phenomenon but may also be associated with ataxia and developmental delay.
METHODS
METHODS
We report eight children with PTU; six of them also exhibiting symptoms of ataxia and/or developmental delay. Treatment with carbonic anhydrase inhibition was offered to children with persisting and/or severe forms.
RESULTS
RESULTS
Whole-exome sequencing and genome-wide array analysis (n = 7) did not reveal mutations in the three known genes associated with PTU (CACNA1A, GRID2, SEPSECS), whereas by MLPA a heterozygous deletion of exon 31 of the CACNA1A gene could be detected in one patient, her mother and two further family members. Further exome and array analysis showed no recurrent variants in potentially novel PTU-related genes in more than one patient. A de novo variant at a highly conserved position in the SIM1 gene was detected in one patient, for which a pathogenic effect could be speculated. Carbonic anhydrase inhibition was started in five children and proved at least partially effective in all of them.
CONCLUSION
CONCLUSIONS
Irrespective of the clinical background and the molecular basic mechanism of PTU, therapeutic carbonic anhydrase inhibition was effective in all five children (acetazolamide, n = 3; sultiame, n = 2) who received this treatment.
Identifiants
pubmed: 31810576
pii: S1090-3798(19)30411-8
doi: 10.1016/j.ejpn.2019.11.002
pii:
doi:
Substances chimiques
Carbonic Anhydrase Inhibitors
0
Thiazines
0
sulthiame
I00Q766CZ2
Acetazolamide
O3FX965V0I
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
181-186Informations de copyright
Copyright © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.