The First International Consensus on the Diagnosis, Care and Treatment of Those with SCN8A-Related Disorders
Abstract number :
2.116
Submission category :
4. Clinical Epilepsy / 4A. Classification and Syndromes
Year :
2023
Submission ID :
809
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Gabrielle Conecker, MPH – International SCN8A Alliance, part of Decoding Developmental Epilepsies
JayEtta Hecker, MS – International SCN8A Alliance; Maya Xia, BA – International SCN8A Alliance; Christelle El Achkar, MD – Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology – Boston Children’s Hospital; Cristine Mella Cukiert, MD – Department of Neurosurgery – São Paulo Epilepsy Clinic; Seth DeVries, MD – Pediatric Neurology – Helen DeVos Children’s Hospital; Elizabeth Donner, MD – Division of Neurology – Hospital for Sick Children; Mark Fitzgerald, MD – Division of Neurology – Children’s Hospital of Philadelphia; Elena Gardella, MD PhD – Danish Epilepsy Center; Michael Hammer, PhD – Shay Emma Hammer Research Foundation – International SCN8A Alliance; Anaita Hegde, MD – Department of Pediatric Neurology – Jaslok Hospital and Research Centre; Chunhui Hu, MD – Department of Neurology – Children’s Hospital of Fudan University; Tian Luo, MD – Department of Neurology – Children’s Hospital of Fudan University; John Schreiber, MD – Department of Neurology – Children’s National Hospital; Nicola Specchio, MD – Division of Neurology – Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico; Yi Wang, MD – Department of Neurology – Children’s Hospital of Fudan University; Tammy Kooistra, - – International SCN8A Alliance; Madeleine Oudin, PhD – Department of Biomedical Engineering, Tufts School of Engineering – Tufts University; Kayla Waldrop, RN – International SCN8A Alliance; J Tyler Youngquist, PhD – International SCN8A Alliance; Dennis Zhang, BA – International SCN8A Alliance; Elaine Wirrell, MD – Child and Adolescent Neurology – Mayo Clinic; M. Scott Perry, MD – Jane and John Justin Institute for Mind Health – Cook Children’s Medical Center
Rationale:
The population of those diagnosed with SCN8A-related disorders is growing and the lack of clear guidelines on the care and treatment of these patients results in uneven access to appropriate care. This project was undertaken to obtain consensus from a range of global, experienced clinicians and a diversity of caregivers on the optimal diagnosis, care and treatment of those with SCN8A.
Methods:
A Core Panel of twelve clinicians and five SCN8A caregivers was established and divided into three workgroups: 1. Diagnosis and phenotypes, 2. Treatments, and 3. Comorbidities and prognosis. Each group completed a structured literature review and developed questions for the first round of the Delphi survey. A larger international group of 29 clinicians and 13 families, spanning 15 countries, served as the expert panel for the modified Delphi process. Three rounds of survey questions were completed to gain increased consensus or clarification on key points. Strong consensus required 80% or more agreement; moderate 67-79%.
Results:
This process confirmed consensus on five distinct phenotypes, including consensus on variations in age of seizure and developmental delay onset and seizure types across phenotypes. Prognosis for epilepsy also varied, with deterioration/stability in Severe DEE and improvements in all other phenotypes. Consensus was strongest for typical features and recommended therapies for the Severe DEE phenotype with more limited consensus for the four other phenotypes - Moderate DEE, SeL(F)IE, Neurodevelopmental Disorders (NDD) with and without seizures. There was strong consensus that in those with Severe DEE, intense challenges with fine and gross motor skills, speech, intellectual disability (ID), sleep disturbances, GI issues and hypotonia are present more than half of the time, while those with NDD most often present with speech delays and ID. There was also high consensus that in those with gain-of-function variants, sodium channel blockers should be considered first-line therapies and levetiracetam avoided. Consensus was also gained on conditions requiring genetic testing, as well as the importance of early diagnosis of SCN8A. Finally, there was high consensus on areas for family counseling and referrals, including a wide spectrum of severity and presence of comorbid conditions, and resources to offer families, such as access to early intervention services and other specialists. Major areas of uncertainty remain and will require further study including the use of robust, readily available clinical and caregiver reported data.
Conclusions:
This important process confirmed five distinct SCN8A phenotypes and provided strong consensus on the typical phenotype and recommended treatment for the Severe DEE phenotype and some features of other phenotypes. This work will serve as a valuable resource for clinicians and caregivers to aid in more targeted diagnosis, treatment and care for those with SCN8A-related disorders.
Funding: Funding provided by the International SCN8A Alliance with support from SCN8A Italy,
SCN8A Netherlands and SCN8A families.
Clinical Epilepsy