Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review.
Pediatr Neurol
; 97: 18-25, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30928302
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espasmos Infantis
/
Proteínas Serina-Treonina Quinases
/
Síndromes Epilépticas
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Pediatr Neurol
Assunto da revista:
NEUROLOGIA
/
PEDIATRIA
Ano de publicação:
2019
Tipo de documento:
Article