期刊
PEDIATRIC NEUROLOGY
卷 97, 期 -, 页码 18-25出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.pediatrneurol.2019.02.015
关键词
CDKL5 deficiency disorder; Developmental encephalopathy; Epileptic encephalopathy; Epilepsy genetics; Clinical trials
资金
- National Institute of Neurological Disorders and Stroke [U54 HD061222, 1K23 NS107646-01, 1K12NS089417-01]
- Rocky Mountain Rett Association
- International Foundation for CDKL5 Research
- Ponzio Family Chair in Neurology Research
- NHMRC Senior Research Fellowship [1117105]
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. (C) 2019 Elsevier Inc. All rights reserved.
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