Primidone improves symptoms in TRPM3-linked developmental and epileptic encephalopathy with spike-and-wave activation in sleep.
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
13
03
2023
received:
01
06
2022
accepted:
14
03
2023
medline:
11
5
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
Developmental and epileptic encephalopathy with continuous spike-and-wave activation in sleep (CSWS) or DEE-SWAS is an age-dependent disease, often accompanied by a decline in cognitive abilities. Early successful treatment of CSWS is associated with a better cognitive outcome. We retrospectively analyzed the clinical, electrophysiological, radiological, and genetic data of children with DEE-SWAS associated with melastatin-related transient receptor type 3 gene (TRPM3) missense variants. We report two unrelated children with pharmacoresistant DEE-SWAS and developmental delay/regression and different heterozygous de novo missense variants in the TRPM3 gene (NM_001366145.2; c.3397 T > C/p.Ser1133Pro, c.2004G > A/p.Val1002Met). The variant p.Val1002Met (previously known as p.Val990Met or p.Val837Met) and p.Ser1133Pro were recently shown to result in a gain-of-function effect. Based on this finding, previous drug resistance, and the experimentally demonstrated inhibitory effect of primidone on TRPM3, we initiated an individualized therapy with this drug. In both children, developmental regression was stopped, psychomotor development improved, and CSWS was no longer detectable. To our knowledge, this is the first report of a treatment with primidone in TRPM3-associated CSWS. Our results highlight the importance of early genetic diagnosis in patients with epilepsy and the possibility of precision medicine, which should be considered in the future in individuals with a TRPM3-linked DEE-SWAS.
Substances chimiques
Primidone
13AFD7670Q
TRPM3 protein, human
0
Anticonvulsants
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e61-e68Informations de copyright
© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Arzimanoglou A, Cross HJ. Cognitive impairment and behavioral disorders in encephalopathy related to status epilepticus during slow sleep: diagnostic assessment and outcome. Epileptic Disord. 2019;21(S1):71-5.
Dorris L, O'Regan M, Wilson M, Zuberi SM. Progressive intellectual impairment in children with encephalopathy related to status epilepticus during slow sleep. Epileptic Disord. 2019;21(S1):88-96.
Arican P, Gencpinar P, Olgac Dundar N, Tekgul H. Electrical status epilepticus during slow-wave sleep (ESES): current perspectives. J Pediatr Neurosci. 2021;16(2):91-6.
Veggiotti P, Pera MC, Olivotto S, De Giorgis V. How to manage electrical status epilepticus in sleep. J Clin Neurophysiol. 2016;33(1):3-9.
Gong P, Xue J, Jiao X, Zhang Y, Yang Z. Genetic etiologies in developmental and/or epileptic encephalopathy with electrical status epilepticus during sleep: cohort study. Front Genet. 2021;12:607965.
Veggiotti P, Pera MC, Teutonico F, Brazzo D, Balottin U, Tassinari CA. Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): an update. Epileptic Disord. 2012;14(1):1-11.
Dyment DA, Terhal PA, Rustad CF, Tveten K, Griffith C, Jayakar P, et al. De novo substitutions of TRPM3 cause intellectual disability and epilepsy. Eur J Hum Genet. 2019;27(10):1611-8.
Van Hoeymissen E, Held K, Nogueira Freitas AC, Janssens A, Voets T, Vriens J. Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy. Elife. 2020;9:e57190.
Vriens J, Owsianik G, Hofmann T, Philipp SE, Stab J, Chen X, et al. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. 2011;70(3):482-94.
Wagner TF, Loch S, Lambert S, Straub I, Mannebach S, Mathar I, et al. Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells. Nat Cell Biol. 2008;10(12):1421-30.
Krugel U, Straub I, Beckmann H, Schaefer M. Primidone inhibits TRPM3 and attenuates thermal nociception in vivo. Pain. 2017;158(5):856-67.
Zhao S, Yudin Y, Rohacs T. Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms. Elife. 2020;9:e55634.
Burglen L, Van Hoeymissen E, Qebibo L, Barth M, Belnap N, Boschann F, et al. Gain-of-function variants in the ion channel gene TRPM3 underlie a spectrum of neurodevelopmental disorders. Elife. 2023;12:e81032.
Kang Q, Yang L, Liao H, Yang S, Kuang X, Ning Z, et al. A Chinese patient with developmental and epileptic encephalopathies (DEE) carrying a TRPM3 gene mutation: a paediatric case report. BMC Pediatr. 2021;21(1):256.
Lines MA, Goldenberg P, Wong A, Srivastava S, Bayat A, Hove H, et al. Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia. Am J Med Genet A. 2022;188(6):1667-75.
de Sainte Agathe JM, Van-Gils J, Lasseaux E, Arveiler B, Lacombe D, Pfirrmann C, et al. Confirmation and expansion of the phenotype associated with the recurrent p.Val837Met variant in TRPM3. Eur J Med Genet. 2020;63(8):103942.
Gauthier LW, Chatron N, Cabet S, Labalme A, Carneiro M, Poirot I, et al. Description of a novel patient with the TRPM3 recurrent p.Val837Met variant. Eur J Med Genet. 2021;64(11):104320.
Lenkapothula N, Cascella M. Primidone. Treasure Island (FL): StatPearls; 2022.
Schmidt D, Kupferberg J. Diphenylhydantoin, phenobarbital, and primidone in saliva, plasma, and cerebrospinal fluid. Epilepsia. 1975;16(5):735-41.
Arhan E, Serdaroglu A, Aydin K, Hirfanoglu T, Soysal AS. Epileptic encephalopathy with electrical status epilepticus: an electroclinical study of 59 patients. Seizure. 2015;26:86-93.