TY - JOUR
T1 - International consensus recommendations for the assessment and management of individuals with CDKL5 Deficiency Disorder
AU - Amin, Sam
AU - Monaghan, Marie
AU - Aledo-Serrano, Angel
AU - Bahi-Buisson, Nadia
AU - Chin, Richard
AU - Clarke, Angus J
AU - Cross, J Helen
AU - Demarest, Scott
AU - Devinsky, Orrin
AU - Downs, Jenny
AU - Knight, Elia M Pestana
AU - Olson, Heather
AU - Partridge, Carol-Anne
AU - Stuart, Graham
AU - Trivisano, Marina
AU - Zuberi, Sameer M
AU - Benke, Tim
N1 - Funding Information:
Neuro-rehabilitation services, sometimes referred to neuro-developmental or neuro-disability services, are part of the care of individuals with CDD. Assessing function and response to therapies is important in guiding and interpreting the findings of future research into therapies for CDD (). A collaborative professional and caregiver-based standardized assessment method was designed using four cycles of a Delphi process, the CDD Clinical Severity Assessment (CCSA). This involved clinicians from the International Foundation for CDKL5 Research Centers of Excellence (COE) consortium and the National Institutes of Health' Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History study consortium (U54 HD061222; ClinicalTrials.gov : NCT00299312/ NCT02738281). Initial consensus was provided by clinicians, researchers, industry, patient advisory groups and the parents of a child. The CCSA reviewed 53 items, 27 reported by parents and 26 reported by clinicians. It has recently been developed () and validated to enable its implementation for the assessment of outcome measures, as per FDA requirements (, ).
Funding Information:
JD Consultancy for Marinus, Ultragenyx, Avexis, Anavex, and Newron; any remuneration went to Telethon Kids Institute. MM works as a pediatric researcher with investigator initiated studies funded through industry (PTC Therapeutics). EP is on the advisory board of Marinus Pharmaceuticals and has consulted for Biomarin Pharmaceuticals and Zogenix. JC has acted as an investigator for studies with GW Pharma, Zogenix, Vitaflo, Ovid, Marinius and Stoke Therapeutics. She has been a speaker and on advisory boards for GW Pharma, Biocodex, Zogenix, and Nutricia; all remuneration has been paid to her department. Her research is supported by the National Institute of Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital. She holds as endowed chair at UCL Great Ormond Street Institute of Child Health; she holds grants from NIHR, EPSRC, GOSH Charity, ERUK, the Waterloo Foundation and the Great Ormond Street Hospital Biomedical Research Centre. SA has received funding from GW Pharmaceuticals, Norvartis, PTC Therapeutics, Boston Scientific, Nutricia, UCB, BioMarin, LivaNova, Medtronic, Desitin, Ipsen, CDKL5 UK, TSA and the National Institute for Health Research. HO received consulting fees from Takeda Pharmaceuticals and Zogenix regarding clinical trial design, Ovid Therapeutics regarding clinical trial results, Marinus Pharmaceuticals regarding CDKL5 Deficiency Disorder, and has done consulting for the FOXG1 Research Foundation. TB performed consultancy for Ovid, GW Pharmaceuticals, International Rett Syndrome Foundation, Takeda, Neurogene, Ultragenyx, Zogenix, GrinTherapeutics, Alcyone, Acadia, Neuren and Marinus; Clinical Trials with Acadia, Ovid, GW Pharmaceuticals, Marinus and RSRT; all remuneration has been made to his department. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funding Information:
HO was supported by NINDS K23 NS107646-04, PI Olson. TB was supported by the Ponzio Family Chair in Neurology Research to the Children's Hospital Colorado Foundation.
Publisher Copyright:
Copyright © 2022 Amin, Monaghan, Aledo-Serrano, Bahi-Buisson, Chin, Clarke, Cross, Demarest, Devinsky, Downs, Pestana Knight, Olson, Partridge, Stuart, Trivisano, Zuberi and Benke.
PY - 2022/6/20
Y1 - 2022/6/20
N2 - CDKL5 Deficiency Disorder (CDD) is a rare, X-linked dominant condition that causes a developmental and epileptic encephalopathy (DEE). The incidence is ~ 1:40,000 and 1:60,000 live births. Pathogenic variants in CDKL5 lead to seizures from infancy and severe neurodevelopmental delay. During infancy and childhood, individuals with CDD suffer impairments affecting cognitive, motor, visual, sleep, gastrointestinal and other functions. Here we present the recommendations of international healthcare professionals, experienced in CDD management, to address the multisystem and holistic needs of these individuals. Using a Delphi method, an anonymous survey was administered electronically to an international and multidisciplinary panel of expert clinicians and researchers. To provide summary recommendations, consensus was set, a priori, as >70% agreement for responses. In the absence of large, population-based studies to provide definitive evidence for treatment, we propose recommendations for clinical management, influenced by this proposed threshold for consensus. We believe these recommendations will help standardise, guide and improve the medical care received by individuals with CDD.
AB - CDKL5 Deficiency Disorder (CDD) is a rare, X-linked dominant condition that causes a developmental and epileptic encephalopathy (DEE). The incidence is ~ 1:40,000 and 1:60,000 live births. Pathogenic variants in CDKL5 lead to seizures from infancy and severe neurodevelopmental delay. During infancy and childhood, individuals with CDD suffer impairments affecting cognitive, motor, visual, sleep, gastrointestinal and other functions. Here we present the recommendations of international healthcare professionals, experienced in CDD management, to address the multisystem and holistic needs of these individuals. Using a Delphi method, an anonymous survey was administered electronically to an international and multidisciplinary panel of expert clinicians and researchers. To provide summary recommendations, consensus was set, a priori, as >70% agreement for responses. In the absence of large, population-based studies to provide definitive evidence for treatment, we propose recommendations for clinical management, influenced by this proposed threshold for consensus. We believe these recommendations will help standardise, guide and improve the medical care received by individuals with CDD.
KW - CDKL5 deficiency disorder
KW - Cyclin-Dependent Kinase-Like 5
KW - CDD
KW - developmental and epileptic encephalopathy
KW - care guideline
KW - consensus methods
KW - Delphi methods
U2 - 10.3389/fneur.2022.874695
DO - 10.3389/fneur.2022.874695
M3 - Article
SN - 1664-2295
VL - 13
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 874695
ER -