First Global Consensus for the Diagnosis and Treatment of SCN8A-Related Disorders: A Delphi Project
Abstract number :
2.43
Submission category :
4. Clinical Epilepsy / 4A. Classification and Syndromes
Year :
2022
Submission ID :
2233000
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:29 AM
Authors :
Gabrielle Conecker, MPH – International SCN8A Alliance/Wishes for Elliott; Maya Xia, BS – COMBINEDBrain; JayEtta Hecker, MS – International SCN8A Alliance/Wishes for Elliott; Christelle El Achkar, Christelle.Achkar@childrens.harvard.edu – Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program – Boston Children's Hospital; Cristine Cukiert, MD – Department of Neurosurgery – Sao 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/Wishes for Elliott; Anaita Hegde, MD – Department of Pediatric Neurology – Jaslok Hospital and Research Centre; Chunhui Hu, MD – Department of Neurology – Children's Hospital of Fudan University; Tiao 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 Gesu Children's Hospital; Yi Wang, MD – Children's Hospital of Fudan University; Tammy Kooistra, NA – International SCN8A Alliance/Family Representative; Madelaine Oudin, PhD – Tufts School of Engineering/International SCN8A Alliance-Family Representative; Kayla Waldrop, NA – International SCN8A Alliance/Family Representative; J Tyler Youngquist, PhD – International SCN8A Alliance/Family Representative; Dennis Zhang, NA – International SCN8A Alliance/Family Representative and SCN8A China; Elaine Wirrell, MD – Child and Adolescent Neurology – Mayo Clinic; M. Scott Perry, MD – Jane and John Justin Institute for Mind Health, Neurosciences Center – Cook Children's Medical Center
This is a Late Breaking abstract
Rationale: Patients with pathogenic variants in SCN8A, the gene encoding the Nav1.6 channel, present with a wide spectrum of phenotypes ranging from severe developmental epileptic encephalopathy to benign infantile seizures to neurodevelopmental disorders without seizures. To standardize diagnosis and management of this rare condition, the International SCN8A Alliance convened an expert global panel to develop guidelines for SCN8A-related disorders using a modified Delphi process. We aim to achieve consensus on phenotypic characterization, therapeutic effectiveness, comorbidities and prognosis as well as identify knowledge gaps to guide future research.
Methods: A modified Delphi framework was employed using a geographically diverse panel of expert clinicians and caregivers to provide generalizable consensus. Two co-chairs [a caregiver (GC) and a professional (MSP)], a coordinator (JH) and 3 workgroup leaders (CA, MF, EG) oversaw the literature review for the primary domains of diagnosis/phenotype characterization, treatment and comorbidities/prognosis and were supported by a core panel of caregivers and professionals with experience in SCN8A-related disorders. Following the literature review, the co-chairs (MSP and GC), coordinator (JH) and our process guide (ECW) developed an initial survey which was completed by the core panel and additional global reviewers nominated by the panel and community. We anticipate up to 2 additional survey rounds as necessary to reach consensus (Table 1). Analysis was primarily conducted by a research coordinator (MX).
Results: The core panel was composed of 31 clinicians and 13 caregivers from 5 continents and 13 countries. The majority of clinicians (80%) have >5 years’ experience treating people with SCN8A-related disorders and over half have published on these conditions. A literature review synthesizing 208 peer-reviewed manuscripts on SCN8A-related disorders informed the creation of a 107-question initial survey. Response rate for the first round included 29/31 (93%) clinicians and 12/13 (92%) caregivers. Following the first round, consensus was reached in all primary domains (Table 2) with intent to develop additional questions to further investigate areas of insufficient agreement. Most importantly, 93% of clinicians and 100% of caregivers at least partially agreed SCN8A-related disorders present as 5 primary phenotypes.
Conclusions: Rare disorders are hampered by insufficient knowledge of diagnosis and treatments given the limited experience of any single provider. Using a modified Delphi process, we achieved consensus in several areas of diagnosis and treatment, most importantly confirming 5 core phenotypes of SCN8A-related disorders (Gardella and Møller doi: 10.1111/epi.16319, and Johannesen at al doi:10.1093/brain/awab321). Additional rounds will focus on defining the multitude of comorbid conditions associated with these disorders while seeking further consensus on diagnosis, treatment, comorbidities and prognosis. Through this process, we are fostering a collaborative initiative to pool knowledge, identify gaps and inform best practices related to the care of those with SCN8A-related disorders.
Funding: International SCN8A Alliance
Clinical Epilepsy