Table 2.
Clinical reports of drug response in myotonic SCN4A mutation carriers
| Mutation | Reference | Response to drug (dose/day) | Number of individuals and other information |
| p.Ile215Thr (c.644T>C) | [46] | NR to PHE (nd), USE to QUI (nd), positive to MEX (nd) | (n = 1) |
| positive to MEX (400 mg) | (n = 1) | ||
| positive to MEX (nd) | (n = 1) | ||
| p.Gly241Val (c.722G>T) | [46] | NR to MEX (nd), PHE (nd), ACZ (nd), and CBZ (nd) | (n = 1) |
| p.Asn440Lys (c.1320T>G) | [47] | positive to ACZ (nd) and HCT (nd) | (n = 10, 1 kindred), myotonia with exercise induced weakness |
| p.Val445Met (c.1333G>A) | [48] | NR or USE with MEX (600 mg), QUI (975 mg), PHE (400 mg), CBZ (1,200 mg), TOC (1,200 mg), ACZ (500 mg), diazepam (10 mg), baclofen (80 mg), and cyclobenzaprine (40 mg) | (several individuals from 1 kindred) |
| positive to FLE (nd) | (n = 1 from the kindred as above) | ||
| [49] | positive to MEX (600 mg) | (n = 1) | |
| positive to PRC (3,000 mg) | (n = 1) | ||
| positive to QUI (600 mg) | (n = 1) | ||
| [50] | positive to MEX (300 mg) | (n = 1) moderate improvement | |
| [36] | positive to RAN (2,000 mg) | (n = 3) | |
| [51] | positive to MEX (nd) | (n = 1) | |
| p.Glu452Lys (nd) | [52] | NR to GAB (nd), positive to PHE (400 mg) | (n = 1) |
| p.Phe671Ser (nd) | [52] | NR to PHE (nd), positive to CBZ (nd) | (n = 1) |
| p.Leu689Phe (c.2065C>T) | [53] | positive to ACZ (250–500 mg) | (n = 1) |
| [54] | positive to PHE (nd) and ACZ (nd) | (n = 1) | |
| p.Ile693Leu (c.2077A>C) | [55] | NR to CBZ (nd), positive to PHE, MEX, or ACZ (nd) | (n = 1) |
| p.Ile693Thr (c.2078T>C) | [56] | positive to Mg2 + (3,600 mg) | (n = 1), aggravated symptoms with hypomagnesemia and hypocalcemia |
| [57] | USE with ACZ (5 mg/kg) | (n = 1) | |
| p.Leu703Pro (c. 2108T>C) | [53] | NR to CBZ (800 mg), positive to ACZ (250–1,000 mg) | (n = 1), headache at the highest ACZ doses |
| [33] | NR to MEX (600 mg) | (n = 1) | |
| p.Thr704Met (c. 2111C>T) | [58] | NR to ACZ (1,000 mg) | (n = 2), hyperPP+PMC |
| NR to ACZ (1,000 mg) and HCT (500 mg) | (n = 1), hyperPP+PMC | ||
| NR to ACZ (1,000 mg) and SLB (6 mg p.o. or 200μg nasally) | (n = 1), hyperPP+PMC | ||
| p.Leu796Val (c. 2389C>G) | [59] | positive to CBZ (36 mg/kg) | (n = 1), respiratory failure |
| [60] | positive to CBZ (20 mg/kg) | (n = 1), myotonic myopathy | |
| p.Arg1148Cys (nd) | [33] | NR to MEX (600 mg) | (n = 1), subtherapeutic plasma concentration |
| p.Pro1158Leu (c. 3473C>T) | [61] | NR to CBZ (nd), USE with MEX (200 mg), positive to FLE (70 mg) | (n = 1), myotonia permanens |
| p.Pro1158Ser (c. 3472C>T) | [62] | positive to ACZ (nd) | (n = 1), myotonia improvement but weakness worsening |
| p.Ile1160Val (c. 3478A>G) | [50] | positive to ACZ (500 mg) | (n = 1), significant improvement |
| p.Gly1292Asp (c.3875A>G) | [63] | NR to MEX (300 mg) | (n = 1) |
| p.Val1293Ile (c. 3877G>A) | [64] | positive to MEX (400 mg) | (n = 1) |
| [50] | positive to MEX (600 mg) | (n = 1), significant improvement | |
| [65] | USE with MEX (200 mg) | (n = 1) | |
| positive to MEX (400 mg) | (n = 1) | ||
| p.Asn1297Lys (c.3891C>A) | [23] | NR to CBZ (20 mg/kg), positive but unstained to MEX (17 mg/kg) | (n = 1), SNEL, dies at 20 months from cardiorespiratory arrest |
| p.Phe1298Cys (c.3893T>G) | [65] | USE with MEX (400 mg) | (n = 1), moderate improvement |
| p.Gly1306Ala (c.3917G>C) | [33] | positive to MEX (600 mg) | (n = 2) |
| [66] | NR to MEX, ACZ, and CBZ (nd) | (n = 1) | |
| p.Gly1306Glu (c.3917G>A) | [67] | NR to MEX (720 mg), oxcarbazepine (nd), and thiazide diuretics (nd), positive to ACZ (500 mg) | (n = 1) |
| [24] | positive to CBZ (40 mg/kg) | (n = 1), SNEL | |
| positive to MEX (15 mg/kg) | (n = 1), SNEL | ||
| [68] | PR to CBZ (600 mg), HQD (600 mg), TOC (1,200 mg), and MEX (800 mg), positive to FLE (200 mg) | (n = 2, mother and son), myotonia permanens | |
| [69] | positive to MEX+ACZ (nd) | (n = 1), SNEL | |
| positive to CBZ (12 mg(kg) | (n = 1), SNEL | ||
| [70] | positive to CBZ (20 mg/kg) | (n = 3), SNEL | |
| [26] | NR to CBZ (20 mg/kg), MEX (15 mg/kg), and ACZ (125 mg), positive to FLE (100 mg) | (n = 1), SNEL | |
| [71] | USE with FLE (200 mg) and HQD (300 mg), positive to MEX (1,200 mg) | (n = 1), SNEL Brugada syndrome with FLE and diarrhea with HQD | |
| [57] | positive to CBZ (200 mg*) | (n = 7/8) | |
| USE with CBZ (200 mg*) | (n = 1/8) | ||
| positive to ACZ (250 mg*) | (n = 4/6) | ||
| USE with ACZ (250 mg*) | (n = 2/6) | ||
| positive to PHE (nd) | (n = 1) | ||
| positive to MEX (400 mg) | (n = 1) | ||
| p.Gly1306Val (c.3917G>T) | [33] | positive to MEX (600 mg) | (n = 5) |
| NR to MEX (600 mg) | (n = 1), concomitant stable angina pectoris | ||
| [36] | NR to RAN (2,000 mg) | (n = 2) | |
| p.Thr1313Met (c.3938C>T) | [72] | NR to ACZ (250 mg), positive to MEX (850 mg) | (n = 2, 1 kindred) |
| [73] | positive to MEX (600–1,200 mg) | (n = 3, 1 kindred) | |
| [74] | NR to MEX (200 mg), USE with higher doses | (n = 1) | |
| [75] | USE with MEX (400 mg), positive to PRO (325 mg) | (n = 1) | |
| [50] | USE with MEX (nd) | (n = 1) | |
| [76] | USE with MEX (400 mg), positive to FLE (200 mg) | (n = 8, 1 kindred) | |
| [77] | positive to ACZ (500 mg) | (n = 1), paramyotonia improved but not persistent weakness | |
| NR to ACZ (250 mg) | (n = 1) | ||
| NR to MEX (150 mg) | (n = 1) | ||
| p.Leu1436Pro (nd) | [78] | NR to ACZ (nd) | (n = 2) |
| PR and USE to ACZ (nd) | (n = 1), allergic rash with ACZ | ||
| PR to CBZ (600 mg)+AMI (50 mg) | (n = 3), some improvement | ||
| p.Arg1448Cys (c.4342G>A) | [79] | positive on weakness, NR on stiffness ACZ (250 mg) | (n = 1) |
| [80] | NR to ACZ (500 mg), PR to MEX (400 mg) | (n = 1) | |
| [81] | positive to PYR (180 mg) and PHE (300 mg) | (n = 1), PYR resolved exercise-induced weakness and PHE reduced cold-induced stiffness | |
| [36] | positive to RAN (2,000 mg) | (n = 3) | |
| [82] | PR and USE with ACZ (500 mg) | (n = 1), PMC with HypoPP | |
| p.Ile1462Met (c.4386C>G) | [36] | positive to RAN (2,000 mg) | (n = 1) |
| p.Met1476Ile (c.4428G>A) | [83] | NR to QUI, PHE, CBZ, AMI, GAB, and ACZ | (n unknown) |
| positive to MEX (400 mg) | (n = 1) | ||
| p.Ala1481Asp (c.4442C>A) | [84] | NR to ACZ (1,000 mg) and PR to MEX (nd) | (n = 1) |
| p.Val1485Phe (nd) | [33] | positive to MEX (600 mg) | (n = 1) |
| p.Val1589Met (c.4765G>A) | [85] | NR to CBZ and PHE (nd), positive to ACZ (500 mg) | (n = 1) |
| [36] | positive to RAN (2,000 mg) | (n = 1) | |
| p.Met1592Val (c.4774A>G) | [86] | NR to ACZ (nd), PR with PHE i.v. (nd), positive to MEX (nd) | (n = 1) |
| p.Gln1633Glu (c.4897C>G) | [87] | positive to MEX (nd) | (n = 3, 1 kindred), myotonia permanens |
| p.Phe1705Ile (c.5113T>A) | [88] | PR to MEX (nd) | (n = 1) |
ACZ: acetazolamide; AMI: amitriptyline; CBZ: carbamazepine; FLE: flecainide; GAB: gabapentin; HCT: hydrochlorothiazide; HQD: hydroquinidine; hyperPP: hyperkalemic periodic paralysis; MEX: mexiletine; nd: not defined; NR: non responder; PHE: phenytoin; QUI: quinine; PMC: paramyotonia congenita; PR: partial response; PRC: procainamide; PRO: propafenone; PYR: pyridostigmine; RAN: ranolazine; SNEL: severe neonatal episodic laryngospasm; TOC: tocainide; USE: untolerated side effects; *mean value.