SCN8A heterozygous variants are associated with anoxic-epileptic seizures

TY - JOUR

T1 - SCN8A heterozygous variants are associated with anoxic-epileptic seizures

AU - Ranza, Emmanuelle

AU - Z'Graggen, Werner

AU - Lidgren, Mathias

AU - Beghetti, Maurice

AU - Guipponi, Michel

AU - Antonarakis, Stylianos E.

AU - Absoud, Michael

AU - Goyal, Sushma

AU - Pal, Deb K.

AU - Korff, Christian M.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Anoxic-epileptic seizures (AES) are rare outcomes of common childhood reflex anoxic syncope that trigger a true epileptic seizure. The term AES was coined by Stephenson in 1983, to differentiate these events from convulsive syncopes and the more common reflex anoxic syncopes. A genetic susceptibility for AES has been postulated; but, its molecular basis has up to now been elusive. We report here two illustrative cases and show the association of de novo SCN8A variants and AES. One of them had focal or generalized seizures and autonomic symptoms triggered by orthostatism; the second had breath-holding spells triggered by pain or exercise leading to tonic–clonic seizures; both had repeatedly normal EEGs and a family history of reflex syncope. The data of three additional AES patients further suggest, for the first time, a link between SCN8A pathogenic variants and AES. The neurodevelopment of four patients was abnormal. Four of the five SCN8A mutations observed here were previously described in patients with seizure disorders. Seizures responded particularly well to sodium channel blockers. Our observation enriches the spectrum of seizures linked with SCN8A pathogenic variants.

AB - Anoxic-epileptic seizures (AES) are rare outcomes of common childhood reflex anoxic syncope that trigger a true epileptic seizure. The term AES was coined by Stephenson in 1983, to differentiate these events from convulsive syncopes and the more common reflex anoxic syncopes. A genetic susceptibility for AES has been postulated; but, its molecular basis has up to now been elusive. We report here two illustrative cases and show the association of de novo SCN8A variants and AES. One of them had focal or generalized seizures and autonomic symptoms triggered by orthostatism; the second had breath-holding spells triggered by pain or exercise leading to tonic–clonic seizures; both had repeatedly normal EEGs and a family history of reflex syncope. The data of three additional AES patients further suggest, for the first time, a link between SCN8A pathogenic variants and AES. The neurodevelopment of four patients was abnormal. Four of the five SCN8A mutations observed here were previously described in patients with seizure disorders. Seizures responded particularly well to sodium channel blockers. Our observation enriches the spectrum of seizures linked with SCN8A pathogenic variants.

KW - AES

KW - anoxic-epileptic seizures

KW - childhood epilepsy

KW - SCN8A

KW - sodium channel blockers

UR - http://www.scopus.com/inward/record.url?scp=85079412863&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.61513

DO - 10.1002/ajmg.a.61513

M3 - Article

C2 - 32040247

AN - SCOPUS:85079412863

SN - 1552-4825

VL - 182

SP - 1209

EP - 1216

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

IS - 5

ER -