SCN8A encephalopathy: Research progress and prospects.
On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care.
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, U.S.A.
Miriam H
MH
Meisler
Department of Neurology, Children's National Health System, Washington, District of Columbia, U.S.A.|Center for Genetic Medicine Research, Children's National Health System, Washington, District of Columbia, U.S.A.
Guy
G
Helman
ARL Division of Biotechnology, University of Arizona, Tucson, Arizona, U.S.A.
Michael F
MF
Hammer
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, U.S.A.
Brandy E
BE
Fureman
Department of Neurology, Children's National Health System, Washington, District of Columbia, U.S.A.|Center for Neuroscience Research, Children's National Health System, Washington, District of Columbia, U.S.A.
William D
WD
Gaillard
Microbiology & Molecular Genetics and Anatomy & Neurobiology, University of California, Irvine, California, U.S.A.
Alan L
AL
Goldin
Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka, Japan.
Shinichi
S
Hirose
Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka, Japan.
Atsushi
A
Ishii
Biostatistics and Epidemiology, RTI International, Rockville, Maryland, U.S.A.
Barbara L
BL
Kroner
Department of Neurology, School of Medicine, University of California Davis, Sacramento, California, U.S.A.
Christoph
0000-0001-8101-2924
C
Lossin
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.
Heather C
HC
Mefford
Department of Neurology, University of Michigan Medical Center and VA Ann Arbor Healthcare System, Ann Arbor, Michigan, U.S.A.
Jack M
JM
Parent
Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia, U.S.A.
Manoj
M
Patel
Department of Neurology, Children's National Health System, Washington, District of Columbia, U.S.A.
John
J
Schreiber
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, U.S.A.
Randall
R
Stewart
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, U.S.A.
Vicky
V
Whittemore
Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, U.S.A.
Karen
K
Wilcox
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, U.S.A.
Jacy L
JL
Wagnon
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
Phillip L
PL
Pearl
Department of Neurology, Children's National Health System, Washington, District of Columbia, U.S.A.|Center for Genetic Medicine Research, Children's National Health System, Washington, District of Columbia, U.S.A.|Department of Integrated Systems Biology and Pediatrics, George Washington University, Washington, District of Columbia, U.S.A.
Adeline
A
Vanderver
Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.|Department of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.|Florey Institute of Neurosciences and Mental Health, Melbourne, Victoria, Australia.
Ingrid E
IE
Scheffer
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001927:Brain Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004831:Epilepsies, Myoclonic / Q000188:drug therapy / Q000235:genetics; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013559:Symbiosis / Q000235:genetics*
D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; C100681:SCN8A protein, human
Bioregistry; Drug screening; Encephalopathy; Mutation; Nav1.6; SCN8A; Sodium channel