Severity Assessment in CDKL5 Deficiency Disorder.
Autonomic Nervous System Diseases
/ etiology
Child
Clinical Trials as Topic
/ statistics & numerical data
Cognition Disorders
/ etiology
Delphi Technique
Epileptic Syndromes
/ complications
Humans
Movement Disorders
/ etiology
Severity of Illness Index
Spasms, Infantile
/ complications
Speech Disorders
/ etiology
Surveys and Questionnaires
Symptom Assessment
/ methods
Vision Disorders
/ etiology
CDKL5
Cortical visual impairment
Epilepsy
Intellectual disability
Rare disorder
Severity assessment
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:
30
12
2018
revised:
18
03
2019
accepted:
19
03
2019
pubmed:
31
5
2019
medline:
2
6
2020
entrez:
1
6
2019
Statut:
ppublish
Résumé
Pathologic mutations in cyclin-dependent kinase-like 5 cause CDKL5 deficiency disorder, a genetic syndrome associated with severe epilepsy and cognitive, motor, visual, and autonomic disturbances. This disorder is a relatively common genetic cause of early-life epilepsy. A specific severity assessment is lacking, required to monitor the clinical course and needed to define the natural history and for clinical trial readiness. A severity assessment was developed based on clinical and research experience from the International Foundation for CDKL5 Research Centers of Excellence consortium and the National Institutes of Health Rett and Rett-Related Disorders Natural History Study consortium. An initial draft severity assessment was presented and reviewed at the annual CDKL5 Forum meeting (Boston, 2017). Subsequently it was iterated through four cycles of a modified Delphi process by a group of clinicians, researchers, industry, patient advisory groups, and parents familiar with this disorder until consensus was achieved. The revised version of the severity assessment was presented for review, comment, and piloting to families at the International Foundation for CDKL5 Research-sponsored family meeting (Colorado, 2018). Final revisions were based on this additional input. The final severity assessment comprised 51 items that comprehensively describe domains of epilepsy; motor; cognition, behavior, vision, and speech; and autonomic functions. Parental ratings of therapy effectiveness and child and family functioning are also included. A severity assessment was rapidly developed with input from multiple stakeholders. Refinement through ongoing validation is required for future clinical trials. The consensus methods employed for the development of severity assessment may be applicable to similar rare disorders.
Sections du résumé
BACKGROUND
Pathologic mutations in cyclin-dependent kinase-like 5 cause CDKL5 deficiency disorder, a genetic syndrome associated with severe epilepsy and cognitive, motor, visual, and autonomic disturbances. This disorder is a relatively common genetic cause of early-life epilepsy. A specific severity assessment is lacking, required to monitor the clinical course and needed to define the natural history and for clinical trial readiness.
METHODS
A severity assessment was developed based on clinical and research experience from the International Foundation for CDKL5 Research Centers of Excellence consortium and the National Institutes of Health Rett and Rett-Related Disorders Natural History Study consortium. An initial draft severity assessment was presented and reviewed at the annual CDKL5 Forum meeting (Boston, 2017). Subsequently it was iterated through four cycles of a modified Delphi process by a group of clinicians, researchers, industry, patient advisory groups, and parents familiar with this disorder until consensus was achieved. The revised version of the severity assessment was presented for review, comment, and piloting to families at the International Foundation for CDKL5 Research-sponsored family meeting (Colorado, 2018). Final revisions were based on this additional input.
RESULTS
The final severity assessment comprised 51 items that comprehensively describe domains of epilepsy; motor; cognition, behavior, vision, and speech; and autonomic functions. Parental ratings of therapy effectiveness and child and family functioning are also included.
CONCLUSIONS
A severity assessment was rapidly developed with input from multiple stakeholders. Refinement through ongoing validation is required for future clinical trials. The consensus methods employed for the development of severity assessment may be applicable to similar rare disorders.
Identifiants
pubmed: 31147226
pii: S0887-8994(18)31324-9
doi: 10.1016/j.pediatrneurol.2019.03.017
pmc: PMC6659999
mid: NIHMS1530407
pii:
doi:
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
38-42Subventions
Organisme : Medical Research Council
ID : MC_PC_14140
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : U54 HD083211
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD061222
Pays : United States
Organisme : NINDS NIH HHS
ID : K12 NS089417
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001102
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS107646
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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