CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development.
CDKL5 deficiency disorder
cortical visual impairment
hypermotor-tonic-spasms sequence
hypsarrhythmia
spasms
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
13
12
2018
revised:
20
06
2019
accepted:
20
06
2019
pubmed:
18
7
2019
medline:
16
4
2020
entrez:
18
7
2019
Statut:
ppublish
Résumé
The cyclin-dependent kinase like 5 (CDKL5) gene is a known cause of early onset developmental and epileptic encephalopathy, also known as CDKL5 deficiency disorder (CDD). We sought to (1) provide a description of seizure types in patients with CDD, (2) provide an assessment of the frequency of seizure-free periods and cortical visual impairment (CVI), (3) correlate these features with genotype and gender, and (4) correlate these features with developmental milestones. This is a cohort study of patients with CDD. Phenotypic features were explored and correlated with gene variant grouping and gender. A developmental score was created based on achieving seven primary milestones. Phenotypic variables were correlated with the developmental score to explore markers of better developmental outcomes. Multivariate linear regression was used to account for age at last visit. Ninety-two patients with CDD were seen during the enrollment period. Eighteen were male (19%); median age at last visit was 5 years (interquartile range = 2.0-11.0). Eighty-one percent of patients developed epileptic spasms, but only 47% of those also had hypsarrhythmia. Previously described hypermotor-tonic-spasms sequence was seen in only 24% of patients, but 56% of patients had seizures with multiple phases (often tonic and spasms). Forty-three percent of patients experienced a seizure-free period ranging from 1 to >12 months, but only 6% were still seizure-free at the last visit. CVI was present in 75% of all CDD patients. None of these features was associated with genotype group or gender. CVI was correlated with reduced milestone achievement after adjusting for age at last visit and a history of hypsarrhythmia. The most common seizure types in CDD are epileptic spasms (often without hypsarrhythmia) and tonic seizures that may cluster together. CVI is a common feature in CDD and is correlated with achieving fewer milestones.
Identifiants
pubmed: 31313283
doi: 10.1111/epi.16285
pmc: PMC7098045
mid: NIHMS1037781
doi:
Substances chimiques
Protein Serine-Threonine Kinases
EC 2.7.11.1
CDKL5 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1733-1742Subventions
Organisme : NINDS NIH HHS
ID : 1K23 NS107646-01
Pays : United States
Organisme : NINDS NIH HHS
ID : 1K12NS089417-01
Pays : United States
Organisme : Rocky Mountain Rett Association
Pays : International
Organisme : NICHD NIH HHS
ID : U54 HD061222
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS107646
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 HD061222
Pays : United States
Organisme : International Foundation for CDKL5 Research
Pays : International
Organisme : NINDS NIH HHS
ID : K12 NS089417
Pays : United States
Organisme : NINDS NIH HHS
ID : 5K12NS079414-02
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.
Références
Epilepsia. 2017 Dec;58(12):2098-2103
pubmed: 29105055
Brain. 2008 Oct;131(Pt 10):2647-61
pubmed: 18790821
Epilepsia. 2002 Jul;43(7):757-63
pubmed: 12102680
Neurology. 2011 Apr 19;76(16):1436-8
pubmed: 21502606
Am J Med Genet A. 2012 Jul;158A(7):1612-9
pubmed: 22678952
Mol Syndromol. 2012 Apr;2(3-5):137-152
pubmed: 22670135
Neurol Genet. 2017 Dec 15;3(6):e200
pubmed: 29264392
Orphanet J Rare Dis. 2016 Apr 14;11:39
pubmed: 27080038
Am J Med Genet A. 2016 Nov;170(11):2860-2869
pubmed: 27528505
Seizure. 2017 Jan;44:58-64
pubmed: 27817982
Epilepsia. 2017 Apr;58(4):531-542
pubmed: 28276064
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4386-91
pubmed: 23440208
Epilepsia. 2018 May;59(5):1062-1071
pubmed: 29655203
Epilepsia. 2004 Jul;45(7):781-6
pubmed: 15230702
Pediatr Neurol. 2019 Aug;97:18-25
pubmed: 30928302
Neurology. 2016 Nov 22;87(21):2206-2213
pubmed: 27770071
Neurol Genet. 2016 Aug 22;2(5):e96
pubmed: 27602407
Eur J Paediatr Neurol. 2016 Jan;20(1):147-51
pubmed: 26387070
J Neurodev Disord. 2015;7(1):2
pubmed: 25657822
Dev Med Child Neurol. 2013 May;55(5):480-4
pubmed: 23151060
Br Med J. 1971 Nov 6;4(5783):323-5
pubmed: 4330909
Pediatr Neurol. 2017 Nov;76:3-13
pubmed: 28918222
Infant Behav Dev. 2017 Nov;49:21-30
pubmed: 28688291
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Brain. 2014 Dec;137(Pt 12):3213-22
pubmed: 25338950
Am J Hum Genet. 2004 Dec;75(6):1079-93
pubmed: 15492925
J Neurol. 2013 Feb;260(2):549-57
pubmed: 23052595
Hum Mol Genet. 2017 Jun 15;26(12):2290-2298
pubmed: 28369421
Seizure. 2018 Jul;59:132-140
pubmed: 29852413
Epilepsia. 2008 Jun;49(6):1027-37
pubmed: 18266744
J Child Neurol. 2013 Jul;28(7):937-41
pubmed: 22832775
Front Psychol. 2012 Apr 17;3:111
pubmed: 22529829
Surv Ophthalmol. 1994 Jan-Feb;38(4):351-64
pubmed: 8160108
Pediatr Neurol. 2012 Feb;46(2):101-5
pubmed: 22264704
Dev Med Child Neurol. 2011 Apr;53(4):354-60
pubmed: 21309761