Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review.
Alternative Splicing
Anticonvulsants
/ therapeutic use
Corpus Callosum
/ surgery
Developmental Disabilities
/ etiology
Diet, Ketogenic
Electroencephalography
Epileptic Syndromes
/ genetics
Gastrointestinal Diseases
/ etiology
Humans
Models, Molecular
Movement Disorders
/ etiology
Mutation
Precision Medicine
Protein Conformation
Protein Serine-Threonine Kinases
/ deficiency
Spasms, Infantile
/ genetics
Vagus Nerve Stimulation
Vision Disorders
/ etiology
CDKL5 deficiency disorder
Clinical trials
Developmental encephalopathy
Epilepsy genetics
Epileptic encephalopathy
Journal
Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
06
01
2019
revised:
21
01
2019
accepted:
16
02
2019
pubmed:
1
4
2019
medline:
2
6
2020
entrez:
1
4
2019
Statut:
ppublish
Résumé
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene CDKL5. This unique disorder includes early infantile onset refractory epilepsy, hypotonia, developmental intellectual and motor disabilities, and cortical visual impairment. We review the clinical presentations and genetic variations in CDD based on a systematic literature review and experience in the CDKL5 Centers of Excellence. We propose minimum diagnostic criteria. Pathogenic variants include deletions, truncations, splice variants, and missense variants. Pathogenic missense variants occur exclusively within the kinase domain or affect splice sites. The CDKL5 protein is widely expressed in the brain, predominantly in neurons, with roles in cell proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis, and synapse development. The molecular biology of CDD is revealing opportunities in precision therapy, with phase 2 and 3 clinical trials underway or planned to assess disease specific and disease modifying treatments.
Identifiants
pubmed: 30928302
pii: S0887-8994(19)30012-8
doi: 10.1016/j.pediatrneurol.2019.02.015
pmc: PMC7120929
mid: NIHMS1525618
pii:
doi:
Substances chimiques
Anticonvulsants
0
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
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
18-25Subventions
Organisme : NINDS NIH HHS
ID : K12 NS089417
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS107646
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD061222
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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