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Page 12 of 18 Orsini et al. J Transl Genet Genom 2018;2:16. I https://doi.org/10.20517/jtgg.2018.14

Table 4. Precision therapy: genetic influences and applied methods
Applied Genetic influences
Gene Pathology Therapy
method toxicity
Valproato, clobazam, stiripentol, In vivo X
fenfluramine
Recommended avoidance In vivo X
SCN1A Dravet syndrome
carbamazepine and phenytoin
Controversial recommendations: In vivo X
lamotrigine
SCN8A E KCNQ2 From benign familial seizures to severe form Carbamazepine and phenytoin In vitro
of epileptic encephalopathy early onset
KCNQ2-5 Retigabine In vitro
GRIN2A Early onset epileptic encephalopathy Memantine In vivo
KCNT1 Focal epileptic seizures Quinidine In vivo
POLG-epilepsies Recommended avoidance valproate In vivo X
EPHX1 Kosovan people of Albanian ethnicity and Affected carbamazepine In vivo X
Chinese people with epilepsy pharmacokinetic
SCN1A, ABCC2, UGT2B7 Han Chinese people with epilepsy Affected maintenance dose of In vivo X
oxcarbazepine
Dysplasia, tuber growth and epileptic symptoms in tuberosis sclerosis. Rapamycine In vivo
Haemimegalencephaly. (sirolimus)
Familial focal epilepsy with variable foci, Rapamycine (sirolimus) In vivo
autosomal dominant nocturnal frontal lobe
epilepsy, familial temporal lobe epilepsy,
DEPD5 rolandic epilepsy and other non-lesional
focal childhood epilepsies and focal epilepsy
associated with focal cortical dysplasia,
both familial and sporadic
GATOR1 Focal epilepsy with cortical malformation m-TOR inhibitors In vivo
PRICKLE mutations epilepsy Inhibitors of USP9X In vivo
Glut1 deficiency syndrome and mutations in SLC2A1 Use of ketogenic diet In vivo
ALDH7A Vit-B6 dependent epilepsy Pyridoxine (vit-B6) In vivo
Resistant epilepsy, Dravet syndrome Cannabidiol In vivo
Epileptic spasms in infancy Steroids or ACTH and vigabatrin In vivo
KCN1A Episodic ataxia type 1 Almorexant, ketogenic diet, In vitro
SCN8A SCN1A SCN2A Epileptic encephalopathy Low evidences about Na-channels In vivo
blockers: amiodarone, bepridil,
aprindine, cibenzolin, riluzole
KCNA2 Early infantile epileptic encephalopathy 4-aminopyrimidine and In vitro
acetazolamide
CACNA1A Infantile spasms, West syndrome Ethosuximide In vitro
HCN1 Early infantile epileptic encephalopathy Ivabradine, propofol, isoflurane, In vivo
ketamine, lamotrigine, gabapentin
CHRNA4, CHRNB2 (nAChR) Epileptic encephalopathy nAChR antagonists In vivo
USP9X: ubiquitin-specific peptidase 9 X-linked; ACTH: Adrenocorticotropic Hormone; nAChRs: nicotinic acetylcholine receptors

cost than a late WES. A diagnostic approach with early targeted WES and limited metabolic testing leaded
to 7 additional diagnoses compared to investigation without targeted WES (46/86 vs. 39/86), with lower
[141]
total cost ($455,597 USD vs. $661,103 USD) and lower cost per diagnosis ($9904 USD vs. $16,951 USD) .
Another study was conducted in a neurogenetic clinic of a tertiary hospital in Argentina and confirmed the
[142]
effective WES-based approach . Additional studies on cost-effectiveness in precision medicine in epilepsy
are needed, as healthcare system demands better allocation of its limited resources, still pursuing the best
possible outcome for patients.

CONCLUSION
Mechanisms underlying epilepsy are multiple and it is very difficult to realize “the gold standard” of AED.
Precision medicine is the future for antiepileptic treatment and can bring a better outcome also for some
kind of epilepsy syndrome that in the past had been considered quite intractable. For example, in a particular