TABLE 4.
Master table of the phenotypic characteristics of the various genotypes among monogenic causes in descending order of frequency.
| Serial no gene | Sex | Seizures (age in months); prior epilepsy syndrome if any | Movement disorder (onset: age in months) | Phenotypic characteristics | Treatment response | Outcome until the last follow‐up (age in months) |
|---|---|---|---|---|---|---|
|
1 ALDH7A1 |
M | FC (1), ES (3); prior EIDEE | Absent | MIC, C HYP | FIHT, responded with VGB & pyridoxine | ESC, SF, BC (8) |
|
2 ALDH7A1 |
M | FC (2), ES (5) | Absent | NHC, C HYP | FIHT, response with VGB & pyridoxine | ESC, SF, AMB, BC (12) |
|
3 ALDH7A1 |
M | MC (1), ES (5); prior EIDEE | Absent | NHC, C HYP | RIHT, relapse, response with pyridoxine | ESC, SF, Normal DEV (6) |
|
4 ALDH7A1 |
F | GT (1), ES (4); prior EIDEE | Absent | NHC, C HYP | FIHT, response with pyridoxine | ESC, SF, AMB (22) |
|
5 ALDH7A1 |
M | GT (1), ES (6) | Absent | NHC, C HYP | FIHT, response with pyridoxine | ESC, SF, AMB (48) |
|
6 ALDH7A1 |
M | GT (1), ES (4); prior EIDEE | Absent | NHC, C HYP | FIHT, response with pyridoxine | ESC, SF, AMB (112) |
|
7 ALDH7A1 |
M | GT (1), ES (3); prior EIDEE | Stereotypies (12) | NHC, C HYP | FIHT, response with pyridoxine | ESC, SF, AMB (15) |
|
8 ALDH7A1 |
F | GT (1), ES (4); prior EIDEE | Absent | NHC, C HYP | FIHT, response with pyridoxine | ESC, SF, AMB (16) |
|
9 ALDH7A1 |
F | FUA (1), ES (3); prior EIDEE | Stereotypies (10) | NHC, C HYP, CVI | FIHT, response with pyridoxine | ESC, SF, AMB (12) |
|
10 ALDH7A1 |
M | GT (1), ES (5); prior EIDEE | Absent | NHC, C HYP | FIHT, response with pyridoxine | ESC, SF, AMB (15) |
|
11 SCN2A |
M | ES (18) | Absent | NHC, C HYP | FIHT, response with NZ, NRTP | ESC, SF, NAMB, AU (40) |
|
12 SCN2A |
F | FT, GT (1), ES (3); prior EIDEE | Absent | NHC, C HYP | FIHT, response with VGB, NRTP | ESC, SF, NAMB, BC (67) |
|
13 SCN2A |
F | ES (6) | Stereotypies (12) | MIC, C HYP | FIHT, relapse, response with VGB, NRTP | ESC, SF, NAMB, AU (60) |
|
14 SCN2A |
M | GT (1), ES (3); prior EIDEE | Absent | MIC, C HYP | FIHT, response with NZ | ESC, SF (8) |
|
15 SCN2A |
M | ES (10), GT (18) | Absent | MIC, C HYP | RIHT, relapse, response with VGB | ESC, SF, AMB (36) |
|
16 SCN2A |
F | GT (6), ES (7) | Stereotypies (14) | NHC, C HYP, CLDY | RIHT, relapse, response with VGB | ESC, SF, NAMB, AU (81) |
|
17 SCN2A |
F | GT (2), ES (2); prior EIDEE | Absent | NHC, MS, HTL, HAP, spasticity, CVI, HI | RIHT, relapse, poor responder | PES, DRE, NAMB, LGS, AU (18) |
|
18 CDKL5 |
F | FC, MC (3), ES (5) | Stereotypies (12) | MIC, C HYP, CVI bruxism | FIHT, response with NZ | ESC, DRE, NAMB, AU (72) |
|
19 CDKL5 |
F | ES (4), GT (12) | Stereotypies (84) | MIC, C HYP prominent ears | FIHT, response with NZ | ESC, DRE, NAMB, AU (120) |
|
20 CDKL5 |
F | GT (1), ES (5); prior EIDEE | Absent | MIC, C HYP | FIHT, response with NZ | ESC, DRE, non‐ambulatory, AUHA (60) |
|
21 CDKL5 |
F | GT, MC (1), ES (4) | Stereotypies (24) | NHC, C HYP | FIHT, relapse, response with VGB | ESC, DRE, NAMB, AU (44) |
|
22 CDKL5 |
F | FC (2), ES (4) | Stereotypies (12) | MIC, C HYP | FIHT, response with ZON | ESC, DRE, NAMB, AU (36); EXP due to SUDEP |
|
23 CDKL5 |
M | ES (2) | Choreathetosis and Dystonia (2) | NHC, C HYP, CVI | RIHT, relapse, response with VGB | DRE, LGS, NAMB, AU (46); EXP at 48 m due to AP |
|
24 ALG13 |
F | ES (5) | Stereotypies (12) | MIC, C HYP | RIHT, relapse, response with NZ | ESC, SF, AMB, AU (50) |
|
25 ALG13 |
F | ES (6) | Dystonia (6) | MIC, C HYP, LSE, HTL | RIHT, relapse, response with VGB | ESC, SF, NAMB (12) |
|
26 ALG13 |
M | ES (14), FUBA (14) | Stereotypies (5) | MIC, C HYP | RIHT, relapse, response with VGB | ESC, SF, AMB, AU (47) |
|
27 ALG13 |
F | ES (13) | Stereotypies (5) | MIC, C HYP | RIHT, relapse, response with VGB | ESC, SF, AMB, AU (19) |
|
28 ALG13 |
F | ES (5) | Stereotypies (12) | MIC, C HYP | RIHT, relapse, response with VGB | ESC, SF, NAMB, AU (27) |
|
29 KCNQ2 |
M | FC (2), ES (4) | Absent | NHC, C HYP | FIHT, response with NZ | ESC, SF, NAMB (22) |
|
30 KCNQ2 |
M | MC (1), ES (2) | Absent | MIC, C HYP | RIHT, relapse, response with NZ | ESC, SF, NAMB (26) |
|
31 KCNQ2 |
F | FT (1), GT (1), ES (6); prior EIDEE | Absent | MIC, C HYP | FIHT, response with NZ | PES, DRE, LGS, AUHA (47) |
|
32 KCNQ2 |
F | GT (1), ES (6); prior EIDEE | Dystonia and Choreoathetosis (24) | MIC, C HYP | RIHT, relapse, response with NZ | ESC, DRE, NAMB, AU (36) |
|
33 STXBP1 |
F | ES (2) | Absent | MIC | FIHT, poor responder | PES, SF, NAMB (50) |
|
34 STXBP1 |
M | ES (3) | Dystonia (5) | NHC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF, AMB, BC (24) |
|
35 STXBP1 |
F | FUA (2), ES (3) | Dystonia (5) | NHC | FIHT, response with VGB | PES, SF, NAMB (7) |
|
36 STXBP1 |
F | FUBA (1), ES (3) | Dystonia (6) | NHC, C HYP | FIHT, response with VGB | ESC, SF, AMB, (18) |
|
37 WWOX |
M | FUA (2), ES (4) | Absent | MIC, C HYP | FIHT, response with VGB | ESC, SF (12) |
|
38 WWOX |
F | ES (3) | Absent | MIC, C HYP | RIHT, relapse, response with NZ | ESC, SF, NAMB (12) |
|
39 WWOX |
F | GTC (2), ES (3) | Absent | MIC, C HYP, UTN, SP | FIHT, response with ZON | PES, SF (6) |
|
40 WWOX |
F | ES (2) | Dystonia (8) | MIC, C HYP, LSE UTN, SP, HYTR | FIHT, poor responder, Failed KD | PES, DRE, NAMB (30) |
|
41 SCN1A |
F | ES (10) | Stereotypies (9) | MIC | FIHT, response with VGB | ESC, SF, NAMB, LGS, AUHA (25) |
|
42 SCN1A |
M | ES (5) | Absent | NHC | RIHT, relapse, response with NZ | ESC, DRE, ASE, NAMB, AUHA (40) |
|
43 SCN1A |
F | ES (2), GTC (3) | Absent | MIC | RIHT, relapse, response with VGB | PES, DRE, ASE, AMB, BC (48) |
|
44 SCN1A |
M | ES (24), GTC (6) | Absent | NHC, C HYP | RIHT, relapse, response with NZ | ESC, SF, AMB, HA (92) |
|
45 NTRK2 |
M | ES (6) | Stereotypies and choreoathetosis (6) | NHC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF, NAMB (24) |
|
46 NTRK2 |
M | ES (3), FC (11), GT (11) | Stereotypies and choreoathetosis (9) | NHC, C HYP, CVI | FIHT, response with KD, relapse | PES, DRE, ASE, NAMB, HA (74) |
|
47 NTRK2 |
F | ES (6) | Dystonia and choreoathetosis | NHC | FIHT, response to valproate and clobazam, relapse | PES, SF, NAMB (55) |
|
48 NTRK2 |
M | ES (6), FT (6) | Absent | MC, C HYP | RIHT, relapse, poor responder | ESC, DRE, LGS, NAMB (58) |
|
49 KCNT1 |
M | ES (7) | Absent | NHC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF, AMB (23) |
|
50 KCNT1 |
F | GT (2), FT (2), ES (4) | Absent | MIC, C HYP, CVI | FIHT, relapse, response with VGB | ESC, SF, AMB (24) |
|
51 KCNT1 |
M | FT (2), FTBTC (3),ES (3); Prior EIMFS | Stereotypies (8) | MIC, C HYP | FIHT, poor responder | ESC, DRE, LGS, NAMB, AU (43) |
|
52 SYNGAP1 |
M | ES (11), MA with EM (13) | Stereotypies (18) | NHC, C HYP long face, large ears | RIHT, no requirement of second‐line therapy | ESC, SF, AMB, AU (48) |
|
53 SYNGAP1 |
F | ES (24) | Stereotypies (12) | NHC, C HYP | RIHT, relapse, response with clobazam | ESC, SF, AMB, AU (123) |
|
54 SYNGAP1 |
M | ES (15), MA with EM (18) | Stereotypies (18) | NHC, C HYP | RIHT, relapse, poor responder | ESC, SF, AMB, AUHA (92) |
|
55 SCN3A |
M | ES (18), GTC (20) | Dystonia (6) | MIC, C HYP | RIHT, relapse, Responded with VGB | ESC, DRE, LGS, NAMB, AU (32) |
|
56 SCN3A |
M | ES (12), GTC (18) | Dystonia (9) | MIC | RIHT, No requirement of second‐line therapy | ESC, DRE, AMB, HA (44) |
|
57 SCN3A |
M | ES (2) | Absent | NHC | RIHT, relapse, response with VGB | ESC, SF, AMB (31) |
|
58 SLC2A1 |
M | GTC (2), ES (5) | Absent | MIC, C HYP | FIHT, response with KD | ESC, SF, AMB, AUHA (40) |
|
59 SLC2A1 |
M | ES (14), GTC (10) | Dystonia and choreoathetosis (24) | MIC, C HYP | FIHT, response with KD | ESC, SF, AMB, AU (38) |
|
60 SLC2A1 |
M | ES (13), GTC (11) | Dystonia and choreoathetosis (20) | MIC | FIHT, response with KD | ESC, SF, AMB, AU (24) |
|
61 MECP2 |
F | GT (5), MC (5), ES (10) | Stereotypies (8) and choreoathetosis (12) | MIC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF, AMB, AU, prominent sleep disturbance (39) |
|
62 MECP2 |
F | ES (18) | Stereotypies (8) and ataxia (12) | MIC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF, AMB, AU (27) |
|
63 CPLX1 |
F | ES (3), MC (3) | Absent | MIC, C HYP | FIHT, poor responder | PES, DRE, ASE, NAMB (48) |
|
64 CPLX1 |
M | ES (3) | Absent | NHC, C HYP | FIHT, poor responder | PES, DRE (6) |
|
65 UGP2 |
M | ES (3) | Absent | MIC, C HYP | RIHT, relapse, response with VGB | EXP at 13 months |
|
66 UGP2 |
F | GT (3), ES (4) | Dystonia (4) | MIC, C HYP | FIHT, relapse, response with VGB and ZON | PES, SF, prominently delayed onset and fragmented sleep (8) |
|
67 PPP3CA |
F | ES (3) | Absent | MIC, C HYP, CVI | FIHT, response with ZON | PES, CVI (9) |
|
68 PPP3CA |
F | ES (4), FC (15) | Stereotypies (10) | MIC, C HYP, CVI, HI | FIHT, poor responder | DRE, NAMB, LGS, AU (26) |
|
69 GRM7 |
F | GT (1), ES (11) | Absent | NHC, C HYP | FIHT, poor responder, sedation with ZON | PES, NAMB, AU (17) |
|
70 TBCD |
M | ES (12), FUBA (20), FTBTC (22), GT (24) | Stereotypies (18), dystonia (30) | MIC, C HYP | RIHT, transaminitis with valproate | ESC, DRE, ASE, LGS, AU (52) |
|
71 CHD2 |
M | ES (7) | Absent | NHC, C HYP | RIHT | ESC, SF (12) |
|
72 CDK19 |
M | ES (8) | Absent | MIC, C HYP, CVI, HI, hypotelorism, bulbous nose | FIHT, response with VGB | PES, BC (13) |
|
73 FOXG1 |
F | GT (8), GTC (8), ES (14) | Stereotypies (6), dystonia, and choreo‐athetosis (6) | MIC, C HYP, AUHA | RIHT, relapse, response with VGB | ESC, DRE, ASE, AUHA, prominently decreased sleep (42) |
|
74 NRROS |
M | FUBA (9), ES (18) | Dystonia (30) | MIC, HI | FIHT, poor responder, neuroregression | PES, DRE, NAMB; EXP at 36 months |
|
75 PURA |
F | ES (5) | Stereotypies, dystonia | NHC, HTL, CVI, AU, plagiocephaly | FIHT, response with VGB | ESC, SF, NAMB, AU (51) |
|
76 KANSL1 |
M | ES (12) | Absent | NHC, C HYP, Obesity | Initially started on VGB, response with VGB, relapse, response with NZ | PES, DRE, LGS, NAMB, BC (27) |
|
77 GABBR2 |
M | ES (18) | Stereotypies (12) | NHC, C HYP, AU, BF | FIHT, response with VGB, relapse, response with NZ | ESC, SF, NAMB, AU (36) |
|
78 GRIN1 |
F | GT (2), ES (2); prior EIDEE | Stereotypies (8) | MIC, C HYP | RIHT, relapse, poor responder | PES, AMB, LGS, delayed onset sleep prominently (13) |
|
79 CSNK2A1 |
F | ES (3) | Absent | MIC, C HYP, LSE, MS, MG | RIHT, no requirement of second‐line therapy | ESC, SF (9) |
|
80 PNPO |
F | GT (1), ES (2) | Dystonia (3) | MIC, C HYP | RIHT, relapse, response with VGB, good response to pyridoxine and P‐5P | ESC, SF, AMB (26) |
|
81 CACNA1A |
F | ES (2), GTC (3) | Absent | MIC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF (30) |
|
82 PLPBP |
M | FUBA (2), ES (5) | Absent | NHC | RIHT, relapse, response with NZ | ESC, SF, AMB, AUHA (120) |
|
83 NPRL3 |
F | FT (1), GT (1), ES (3); prior EIDEE | Absent | NHC | RIHT, no requirement of second‐line therapy | ESC, SF (6) |
|
84 PROSC |
M | GT (1), ES (6); Prior EIDEE | Stereotypies (6) | MIC, C HYP | FIHT, response with NZ | ESC, DRE, ASE, LGS, AMB, HA (120) |
|
85 IQSEC2 |
M | FT (6), ES (19), GT (50) | Stereotypies (24) | MIC, C HYP | FIHT, poor responder | ESC, DRE, LGS, AMB, HA (90) |
|
86 CYFIP2 |
M | FC (2), ES (11) | Absent | MIC, C HYP | RIHT, relapse, response with KD | NAMB before death; EXP at 2 y 7 mo of age |
|
87 MBOAT7 |
M | ES (6) | Absent | NHC, C HYP | RIHT, no requirement of second‐line therapy | ESC, SF, NAMB (22) |
|
88 MBD5 |
M | GTC (6), ES (6) | Absent | NHC, C HYP | RIHT, poor responder | ESC, DRE, AMB (30) |
|
89 PPP2R1A |
F | E (4), MC (11) | Stereotypies (9) | NHC, C HYP | FIHT, poor responder | DRE, LGS, AMB, AUHA (132) |
|
90 DNM1 |
M | ES (3) | Absent | MIC, C HYP, CVI, HI | FIHT, poor responder | PES, NAMB (40) |
|
91 NONO |
M | ES (6), GTC (84) | Stereotypies (12) | NHC, C HYP | FIHT, poor responder | PES, AMB, AU (199) |
|
92 EHMT1 |
F | ES (5) | Stereotypies (12) | MIC, C HYP, synophrys, LSE, brachycephaly | RIHT, no requirement of second‐line therapy | ESC, SF, NAMB, AU (20) |
|
93 GNAO1 |
F | GT (2), ES (3) | Dystonia (3) | NHC, C HYP | FIHT, response with NZ | ESC, SF, NAMB (48) |
|
94 PRRT2 |
F | GT (4), ES (7) | Dystonia (5) | NHC | FIHT, response with VGB | ESC, SF (9) |
|
95 AMT |
M | FC (2), ES (3) | Absent | MIC | FIHT, response with NZ | ESC, DRE (10) |
|
96 KMT2C |
M | FC (3), ES (5) | Stereotypies (18) | MIC, C HYP, AU | FIHT, response with NZ | PES, DRE, AMB, AU (108) |
|
97 ADSL |
F | FC (2), ES (15) | Stereotypies | MIC, Long eyebrows | FIHT, response with NZ | ESC, DRE, LGS, NAMB, AU (84) |
|
98 SATB1 |
M | ES (18), FUBA (130), GT (132) | Stereotypies | MIC, LSE | FIHT, response with VGB | ESC, AMB, AUHA (144) |
|
99 PACS2 |
M | ES (5) | MIC, C HYP | FIHT, response with NZ | ESC, NAMB, AUHA (44) | |
|
100 HUWE1 |
M | ES (10), GT (13) | Dystonia and choreoathetosis (12) | MIC, C HYP, BF, flat occiput, LSE, brachydactyly, NPF, deep eyes | RIHT, relapse, response with NZ | ESC, NAMB (20) |
|
101 ASNS |
M | FC (2), MC (2), ES (6) | Stereotypies | MIC | RIHT, relapse, response with ZON | ESC, DRE, AU, EXP at 8 months |
|
102 MIPEP |
M | ES (6), GTC (6) | Severe dystonia (8) | MIC, C HYP | RIHT, relapse, response with VGB | ESC, SF, NAMB (22) |
|
103 PLEKHG2 |
F | GTC (4), MC (4), ES (9) |
Stereotypies Dystonia (6) |
MIC, C HYP, AU | RIHT, no requirement of second‐line therapy | ESC, SF, AMB, AU (132) |
|
104 SCN8A |
M | GT (5), FUBA (6), ES (8) | Stereotypies | NHC, C HYP, HTL, LSE, deep eyes | FIHT, responded with NZ, No response to phenytoin | ESC, SF, AU (10) |
|
105 MT‐ND5 |
F | ES (6) | Dystonia (10) | NHC, C HYP, BF, large ears | RIHT, no requirement of second‐line therapy | ESC, SF, NAMB, neuroregression following varicella around 2 y of age (30) |
Abbreviations: AMB, ambulatory; AP, aspiration pneumonia; ASE, admission for status epilepticus in the preceding 2 y at last visit; AU, autistic; AUHA, autistic and hyperactive; BC, behavioral concerns like excessive anger, disobedient, self‐injurious behavior, etc.; BF, broad forehead; C HYP, central hypotonia; CLDY, clinodactyly; CVI, cortico visual impairment; DEV, development; DRE, drug refractory epilepsy; EIDEE, early infantile developmental and epileptic encephalopathy; EIMFS, epilepsy of infancy with migrating focal seizures; ESC, epileptic spasms under control; ES, epileptic spasms; EXP, expired; FC, focal clonic; F, female; FIHT, failed initial hormonal therapy; FTBTC, focal tonic to bilateral tonic clonic; FT, focal tonic; FUA, focal unaware seizure with automatisms; FUBA, focal unaware seizure with behavioral arrest; GT, generalized tonic; HA, hyperactive; HAP, high arched palate; H, hormonal therapy; HI, hearing impairment; HTL, hypertelorism; IESS, infantile epileptic spasms syndrome; LSE, low set ears; MC, myoclonic; MIC, microcephaly; M, male; MS, mongoloid slant; NAMB, non‐ambulatory; NHC, normal head circumference; NPF, narrow palpebral fissure; NRTP, no response to phenytoin; PES, persistent epileptic spasms; RIHT, responded to initial hormonal therapy; SF, seizure free.