Table 3

List of the 23 patients where a PM strategy was tried and was not successful (<50% seizure reduction)

Gene variant and detailsAge at clinical diagnosis (years)Age at genetic diagnosis (years)No of ASMs tried before genetic diagnosis/other non-medical treatmentChanges of treatment following genetic diagnosis, and details of outcomeAge at last follow-up (years)Diagnostic assessment following genetic diagnosisPrevious ASMs worsening seizure control
Heterozygous CHRNA4 (c.851C>T, p.Ser284Leu), likely pathogenic16227Introduction of nicotine patches and zonisamide, both ineffective24NoneNone
Heterozygous CHRNA4 (c.868C>A, p.Leu290Met), uncertain significance24247Introduction of galantamine, ineffective33NoneNone
Heterozygous KCNA2 (c.894G>T, p.Leu298Phe), likely pathogenic23613Introduction of 4-aminopyridine, seizure deterioration41ECGNone
Heterozygous SCN1A (c.264+3 del), uncertain significance383814 plus VNSWithdrawal of carbamazepine, introduction of cannabidiol and zonisamide, ineffective51NoneNone
Heterozygous SCN1A (c.603-2A>G, p.(?)), pathogenic202013 plus VNSWithdrawal of carbamazepine, introduction of cannabidiol and stiripentol, seizure reduction <50%31NoneLamotrigine
Hterozygous SCN1A (c.1754dup), pathogenic292510Withdrawal of carbamazepine, seizure control stable, improved cognition29ECGNone
Heterozygous SCN1A (c.2435C>T, p.Thr812Ile), uncertain significance1515Five plus callosotomy and VNSWithdrawal of phenytoin, seizure worsening20UnknownUnknown
Heterozygous SCN1A (c.2834_2847del, p(Phe945Trpfs*47), pathogenic313118 plus VNSWithdrawal of carbamazepine, seizure reduction <50%38NoneLamotrigine
Heterozygous SCN1A (c.2836C>T, p.Arg946Cys), likely pathogenic1717Eight plus KD and VNSWithdrawal of lacosamide and re-introduction of valproate, ineffective18NoneNone
Heterozygous SCN1A (c.3797A>C, p.Glu1266Ala), likely pathogenic1626Ten plus KDWithdrawal of carbamazepine, introduction of valproate and cannabidiol, seizure reduction <50%38NoneLamotrigine
Heterozygous SCN1A (c.4205_4208del, p.Arg1402Metfs*9), pathogenic41714 plus KDWithdrawal of phenobarbitone, introduction of stiripentol and zonisamide, seizure reduction <50%29NoneCarbamazepine, lamotrigine
Heterozygous SCN1A (c.4384T>C; p.Tyr1462His), likely pathogenic141815 plus VNSIntroduction of clobazam, withdrawal of primidone and phenobarbitone, seizure control stable, cognition improvement39NoneLamotrigine, levetiracetam
Heterozygous SCN1A (c.4396_4372dupCTGT; p.Tyr1458Serfs), pathogenic27289Withdrawal of oxcarbazepine, initial >50% seizure reduction but not sustained37NoneNone
Heterozygous SCN1A (c.4568T>C p.I1523T), likely pathogenic364017Withdrawal of lamotrigine, introduction of stiripentol, ineffective47NoneNone
Heterozygous SCN1A (c.5092G>T, p.Glu1698*), likely pathogenic120Ten plus KDWithdrawal of oxcarbazepine, introduction of stiripentol and cannabidiol, seizure reduction <50%25ECGNone
Heterozygous SCN1A (c.5468T>C, p.Met1823Thr), uncertain significanceUnknown5412Withdrawal of oxcarbazepine, introduction of clobazam, seizure reduction <50%61NoneCarbamazepine, phenytoin
Heterozygous SCN2A (c.4037T>A, p.Ile1346Asn), uncertain significance0.117Six plus KDIntroduction of carbamazepine, seizure reduction <50%23ECGNone
Heterozygous SCN2A (c.4949T>C, p.Leu1650Pro), likely pathogenic1147Introduction of phenytoin, severe seizure deterioration19Cardiac assessmentNone
Heterozygous SCN8A (c.2287A>G, p.I763V), likely pathogenic0.5205Introduction of phenytoin, increased dose of carbamazepine, ineffective25NoneNone
Heterozygous SCN8A (c.2921C>G, p.Ala974Gly), pathogenic111012 plus KDIntroduction of phenytoin, ineffective12Cardiac assessmentNone
Heterozygous SLC2A1 (c.1437C>T, p.Pro479=), uncertain significance89Six plus KDIntroduction of KD, effective but not tolerated15NoneNone
Heterozygous TSC2 (c.3671_3674del, p.Asn1224Thrfs*100), pathogenic0.4Unknown8Introduction of everolimus, clinical deterioration including seizure worsening26Multidisciplinary assessment including neurological, renal and cardiac surveillanceNone
Heterozygous TSC2 (c.4639_4642del, p.Val1547Cysfs*28), pathogenic128Nine plus cortical resectionIntroduction of everolimus, ineffective32Multidisciplinary assessment including neurological, renal and cardiac surveillanceNone
  • .ASM, antiseizure medication; KD, ketogenic diet; PM, precision medicine; VNS, vagus nerve stimulation.