Introduction
Method
Participants
Next-generation sequencing
Targeted gene capture and sequencing
ADSL
|
CHD2
|
DHFR
|
GLB1
|
MAGI2
|
PNPO
|
SLC9A6
|
ALDH7A1
|
CHRNA2
|
DIAPH3
|
GLRA1
|
MAPK10
|
POLG
|
SPTAN1
|
ALG13
|
CHRNA4
|
DNAJC6
|
GPR56
|
MBD5
|
PPT1
|
SRPX2
|
ARG1
|
CHRNA7
|
DNM1
|
GPR98
|
MDGA2
|
PROC
|
ST3GAL2
|
ARHGEF15
|
CHRNB2
|
DOCK7
|
GRIN1
|
ME2
|
PRRT2
|
ST3GAL5
|
ARHGEF9
|
CLCN2
|
EEF1A2
|
GRIN2A
|
MECP2
|
RBFOX1
|
STRADA
|
ARX
|
CLCN4
|
EFHC1
|
GRIN2B
|
MEF2C
|
RBFOX2
|
STXBP1
|
ASAH1
|
CLN3
|
ELP4
|
HAX1
|
MFSD8
|
RBFOX3
|
SYNGAP1
|
ATP13A4
|
CLN5
|
EPHB2
|
HDAC4
|
MTHFR
|
RELN
|
SYNJ1
|
ATP1A2
|
CLN6
|
ERBB4
|
HEXA
|
MTOR
|
RYR3
|
SZT2
|
ATP1A3
|
CLN8
|
FASN
|
HEXB
|
NDE1
|
SCN1A
|
TBC1D24
|
ATP6AP2
|
CNTN5
|
FLNA
|
HNRNPH1
|
NEDD4L
|
SCN1B
|
TCF4
|
ATP7A
|
CNTNAP2
|
FOLR1
|
HNRNPU
|
NID2
|
SCN2A
|
TNK2
|
BRAF
|
COX6B1
|
FOXG1
|
IQSEC2
|
NRXN1
|
SCN8A
|
TPP1
|
BSN
|
CSTB
|
FOXP2
|
KCNB1
|
PAFAH1B1
|
SHANK3
|
TSC1
|
CACNA1A
|
CTNNA3
|
GABBR2
|
KCNH5
|
PCDH19
|
SLC13A5
|
TSC2
|
CACNA1H
|
CTSD
|
GABRA1
|
KCNMA1
|
PDHA1
|
SLC19A3
|
TUBA1A
|
CACNB4
|
CYB5R3
|
GABRA6
|
KCNQ2
|
PIGA
|
SLC1A3
|
UBE3A
|
CASR
|
DBH
|
GABRB2
|
KCNQ3
|
PIGV
|
SLC25A22
|
VRK2
|
CDH13
|
DCX
|
GABRB3
|
KCNT1
|
PLCB1
|
SLC2A1
|
WDR45
|
CDH9
|
DEPDC5
|
GABRD
|
LGI1
|
PNKD
|
SLC35A2
|
ZEB2
|
CDKL5
|
DGKD
|
GABRG2
|
LIAS
|
PNKP
|
SLC46A1
|
Data analysis and pathogenicity of candidate variants
Statistical analysis
Results
Clinical diagnosis | Cases | P/LP mutations | P/LP gene(recurrent no.) |
---|---|---|---|
DS | 23 | 16 | SCN1A (16) |
OS | 10 | 2 | KCNQ2 (1), SCN2A (1) |
OS-WS | 2 | 1 | STXBP1 (1) |
WS | 10 | 4 | STXBP1 (1), KCNT1 (1), CDKL5 (1), ADSL (1) |
WS-LGS | 2 | – |
–
|
LGS | 5 | – |
–
|
EIMFS | 2 | – |
–
|
ECSWS | 2 | – |
–
|
EME | 1 | – |
–
|
LKS | 1 | – |
–
|
UEE | 42 | 8 | CACNA1A (1), GABRA1 (1), GABRB3 (1), SCN8A (2), IQSEC2 (1), PCDH19 (1), CHD2 (1) |
Doose | 4 | 1 | SYNGAP1 (1) |
TLE | 1 | – |
–
|
GLUT1-DS | 1 | 1 | SLC2A1 (1) |
Rett | 3 | 1 | MECP2 (1) |
TSC | 5 | 5 | TSC2 (5) |
SWS | 1 | – |
–
|
UE | 57 | 4 | VRK2 (1), ATP1A2 (1), TSC (1), SLC9A6 (1) |
Total | 172 | 43 | – |
Case code | Gene | Gene location | Transcript | cDNA change | Protein change | SIFT | PP2 | MT | HSF | GERP++ | MAF-ExAC | MAF-KG | Parental Origin | ACMG scoring | ACMG pathogenicity | Diagosis |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
13 |
SCN1A
| chr2–166,901,702 | NM_006920 | c.1513A > T | p.K505X | – | – | A | – | 6.17 (C) | – | – |
De novo
| PVS1 + PS2 + PM2 | LP | DS |
23 |
SCN1A
| chr2–166,854,657 166,854,660 a [101] | NM_006920 | c.4331_4334del | p.E1444fs | – | – | – | – | – | – | – |
De novo
| PVS1 + PS1 + PS2 + PM2 | P | DS |
26 |
SCN1A
| chr2–166,870,270 | NM_001165963 | c.3689T>C | p.L1230P | D | D | D | – | 5.28 (C) | – | – |
De novo
| PS2 + PM1 + PM2 + PP3 | LP | DS |
35 |
SCN1A
| chr2–166,900,287 166,900,288 | NM_001165963 | c.1934_1935del | p.V645fs | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | DS |
38 |
SCN1A
| chr2–166,859,121 | NM_006920 | c.G4112T | p.G1371V | D | P | D | – | 5.54 (C) | – | – |
De novo
| PS2 + PM2 | LP | DS |
53 |
SCN1A
| chr2–166,894,306 166,894,337 | NM_001165963 | c.2895_2926del | p.Q965fs | – | – | – | – | – | – | – | Unknown | PVS1 + PM2 | LP | DS |
56 |
SCN1A
| chr2–166,908,355 a [102] | NM_006920 | c.838T > C | p.W280R | D | D | D | – | 5.41 (C) | – | – |
De novo
| PS1 + PS2 + PM2 + PP3 | P | DS |
65 |
SCN1A
| chr2–166,850,927 | NM_006920 | c.4549-1G > C | splicing | – | – | D | + | 5.76 (C) | – | – |
De novo
| PVS1 + PS2 + PM2 | P | DS |
115 |
SCN1A
| chr2–166,848,614 | NM_006920 | c.5138C > A | p.A1713D | D | D | D | – | 5.8 (C) | – | – |
De novo
| PS2 + PM2 + PP3 | LP | DS |
124 |
SCN1A
| chr2–166,848,438 a [103] | NM_006920 | c.5314G > A | p.A1772T | D | D | D | – | 5.69 (C) | – | – |
De novo
| PS1 + PS2 + PM2 + PP3 | P | DS |
130 |
SCN1A
| chr2–166,854,634 166,854,639 a [101] | NM_006920 | c.4352_4356del | p.Y1451Cfs*22 | – | – | – | – | – | – | – |
De novo
| PVS1 + PS1 + PS2 + PM2 | P | DS |
140 |
SCN1A
| chr2–166,911,210 166,911,211 | NM_006920 | c.539delT | p.L180X | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | DS |
148 |
SCN1A
| chr2–166,901,579 | NM_001165963 | c.1636G > T | p.E546X | – | – | A | – | 6.17 (C) | – | – | Unknown | PVS1 + PM2 | LP | DS |
149 |
SCN1A
| chr2–166,894,430 a [104] | NM_006920 | c.2769G > A | p.M923I | D | D | D | – | 5.18 (C) | – | – | Paternal | PS1 + PM2 + PP3 | LP | DS |
162 |
SCN1A
| chr2–166,848,043 166,848,045 | NM_001165963 | c.5740_5742del | p.1914_1914del | – | – | – | – | – | – | – |
De novo
| PS2 + PM2 + PM4 | LP | DS |
172 |
SCN1A
| chr2–166,903,330 | NM_006920 | c.1327G > T | p.E443X | – | – | A | – | 5.31 (C) | – | – |
De novo
| PVS1 + PS2 + PM2 | P | DS |
93 |
SCN2A
| chr2–166,243,416 | NM_001040142 | c.4712T > C | p.I1571T | D | D | D | – | 5.17 (C) | – | – |
De novo
| PS2 + PM1 + PM2 + PP3 | LP | OS |
55 |
KCNQ2
| chr20–62,073,781 a [105] | NM_172107 | c.794C > T | p.A265V | D | P | D | – | 3.38 (C) | – | – |
De novo
| PS1 + PS2 + PM2 | P | OS |
90 |
STXBP1
| chr9–130,423,419 a [53] | NM_003165 | c.364C > T | p.R122X | – | – | A | – | 4.92 (C) | – | – | Unknown | PVS1 + PS1 + PM2 | P | OS-WS |
52 |
ADSL
| chr22–40,745,935 | NM_000026 | c.253C > T | p.R85X | – | – | A | – | 5.59 (C) | – | – | Maternal | PVS1 + PM2 | LP | WS |
chr22–40,742,633 [58] | NM_000026 | c.71C > T | p.P24L | T | B | D | – | 0.153 (N) | – | – | Paternal | PM2 | UC | |||
89 |
KCNT1
| chr9–138,651,532 a [106] | NM_020822 | c.862G > A | p.G288S | T | D | D | – | 5.05 (C) | – | – |
De novo
| PS1 + PS2 + PM1 + PM2 | P | WS |
104 |
CDKL5
| chrX-18,593,592 18,593,593 | NM_003159 | c.265delT | p.F89Lfs*24 | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | WS |
151 |
STXBP1
| chr9–130,428,529 | NM_003165 | c.748C > T | p.Q250X | – | – | A | – | 5.72 (C) | – | – |
De novo
| PVS1 + PS2 + PM2 | P | WS |
29 |
SYNGAP1
| chr6–33,393,659 33,393,662 | NM_006772 | c.274_277del | p.G92fs | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | Doose |
164 |
SLC2A1
| chr1–43,396,517 | NM_006516 | c.296T > G | p.M99R | D | B | D | – | 5.51 (C) | – | – |
De novo
| PS2 + PM2 | LP | GLUT1-DS |
30 |
MECP2
| chrX-153,296,516 a [63] | NM_001110792 | c.799C > T | p.R267X | – | – | A | – | 3.55 (C) | – | – |
De novo
| PVS1 + PS1 + PS2 + PM2 | P | Rett |
32 |
TSC2
| chr16–2,126,095 a [91] | NM_000548 | c.2666C > T | p.A889V | D | D | D | – | 5.09 (C) | – | – | Paternal | PS1 + PM2 + PP3 | LP | TSC |
94 |
TSC2
| chr16–2,130,180 a [107] | NM_000548 | c.3412C > T | p.R1138X | – | – | A | – | 4.74 (C) | – | – |
De novo
| PVS1 + PS1 + PS2 + PM2 | P | TSC |
TSC2
| chr16–2,130,366 a [66] | NM_000548 | c.3598C > T | p.R1200W | D | D | D | – | 4.74 (C) | – | – |
De novo
| PS1 + PS2 + PM2 + PP3 | P | ||
98 |
TSC2
| chr16–2,138,467 | NM_001077183 | c.5079C > G | p.Y1693X | – | – | D | – | 0.137 (N) | – | – | Paternal | PVS1 + PM2 | LP | TSC |
TSC2
| chr16–2,138,465 2,138,466 | NM_001077183 | c.5077delT | p.Y1693fs | – | – | – | – | – | – | – | Paternal | PVS1 + PM2 | LP | ||
7 |
SCN8A
| chr12–52,184,209 a [108] | NM_001177984 | c.4324G > A | p.E1442K | D | D | D | – | 4.68 (C) | – | – | Paternal | PS1 + PM2 + PP3 | LP | UEE |
IQSEC2
| chrX-53,263,621 53,263,622 | NM_001111125 | c.4246_4247insG | p.S1416fs | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | ||
63 |
CACNA1A
| chr19–13,566,019 a [109] | NM_001127221 | c.301G > C | p.E101Q | D | D | D | – | 5.01 (C) | – | – |
De novo
| PS1 + PS2 + PM1 + PM2 + PP3 | P | UEE |
66 |
SCN8A
| chr12–52,200,885 a [110] | NM_001177984 | c.5492G > A | p.R1831Q | D | D | D | – | 4.91 (C) | – | – |
De novo
| PS1 + PS2 + PM2 + PP3 | P | UEE |
69 |
PCDH19
| chrX-99,551,873 99,551,874 | NM_001184880 | c.2849-1G > − | splicing | – | – | – | + | – | – | – | Unknown | PVS1 + PM2 | LP | UEE |
157 |
GABRB3
| chr15–26,812,802 a [111] | NM_021912 | c.761C > T | p.S254F | D | D | D | – | 6.06 (C) | – | – |
De novo
| PS1 + PS2 + PM1 + PM2 + PP3 | P | UEE |
160 |
GABRA1
| chr5–161,309,645 a [112] | NM_001127648 | c.641G > A | p.R214H | D | D | D | – | 5.34 (C) | – | – |
De novo
| PS1 + PS2 + PM1 + PM2 + PP3 | P | UEE |
54 |
CHD2
| chr15–93,540,231 | NM_001271 | c.3640G > T | p.G1214X | – | – | A | – | 5.64 (C) | – | – |
De novo
| PVS1 + PS2 + PM2 | P | UEE |
40 |
VRK2
| chr2–58,312,086 | NM_001130483 | c.C256 + 1G > A | splicing | – | – | D | + | 5.86 (C) | – | – | Unknown | PVS1 + PM2 | LP | UE |
44 |
ATP1A2
| chr1–160,098,521 | NM_000702 | c.1097G > T | p.G366V | D | D | D | – | 4.77 (C) | – | – |
De novo
| PS2 + PM1 + PM2 + PP3 | LP | UE |
68 |
TSC1
| chr9–135,772,854 | NM_000368 | c.2768_2769insC | p.L924Ffs*26 | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | UE |
79 |
SLC9A6
| chrX-135,080,322 135,080,336 | NM_001042537 | c.582_595del | p.Y194fs | – | – | – | – | – | – | – |
De novo
| PVS1 + PS2 + PM2 | P | UE |
Case code | Gender/age | Diagosis | Age of onset | Seizure types | EEG | Brain MRI/CT | Developmental delay | Gene | cDNA change | Protein change | Parental Origin | ACMG pathogenicity |
---|---|---|---|---|---|---|---|---|---|---|---|---|
13 | F/2y6m | DS | 3m | FS, FoS, Myo | FSW | Normal | Yes |
SCN1A
| c.1513A > T | p.K505X |
De novo
| LP |
23 | F/3y | DS | 7m | FS, FoS (A), Myo, FBTC | Multi. FD | Underdeveloped myelin | Yes |
SCN1A
| c.4331_4334del | p.E1444fs |
De novo
| P |
26 | F/5y11m | DS | 5m | FS, SE, FoS (A), Myo, FBTC | FSW | Normal | Yes |
SCN1A
| c.3689T>C | p.L1230P |
De novo
| LP |
35 | M/4y | DS | 3m | FS, SE, GTCS, aAb | Multi. FD | Normal | Yes |
SCN1A
| c.1934_1935del | p.V645fs |
De novo
| P |
38 | F/1y6m | DS | 4m | FS, SE, Myo | FSW | Nonspecific | Yes |
SCN1A
| c.G4112T | p.G1371V |
De novo
| LP |
53 | M/5y | DS | 7m | FS, aAb, Myo, Fos (I) | Multi. FD | Normal | Yes |
SCN1A
| c.2895_2926del | p.Q965fs | Unknown | LP |
56 | F/3y6m | DS | 5m | FS, Myo, GTCS, SE, FoS (A), aAb | Multi. FD | Nonspecific | Yes |
SCN1A
| c.838T > C | p.W280R |
De novo
| P |
65 | M/2y4m | DS | 5m | FS, SE, FoS (A) | FSW | Normal | Yes |
SCN1A
| c.4549-1G > C | splicing |
De novo
| P |
115 | M/2y1m | DS | 8m | FS, FoS (I), FoS (hemi clonic), GTCS | FSW | Enlargement of the subarachnoid space in front of left temporal lobe | Yes |
SCN1A
| c.5138C > A | p.A1713D |
De novo
| LP |
124 | M/3y | DS | 5m | FS, FoS (A), FBTC | FSW | Nonspecific | Yes |
SCN1A
| c.5314G > A | p.A1772T |
De novo
| P |
130 | F/11y | DS | 6m | FS, FoS (A), aAb, Myo, GTCS | Multi. FD | Normal | Yes |
SCN1A
| c.4352_4356del | p.Y1451Cfs*22 |
De novo
| P |
140 | F/1y9m | DS | 3m | FS, GTCS, C, FoS (I) | FSW | Normal | Yes |
SCN1A
| c.539delT | p.L180X |
De novo
| P |
148 | F/6y8m | DS | 4m | FS, GTCS, FoS, aAb | Multi. FD | Normal | Yes |
SCN1A
| c.1636G > T | p.E546X | Unknown | LP |
149 | M/3y6m | DS | 4m | FS, FoS (A), Myo, GTCS | Multi. FD, GSW | Normal | Yes |
SCN1A
| c.2769G > A | p.M923I | Paternal (FS) | LP |
162 | M/4y | DS | 5m | FS, FoS (A), Myo, FBTC | Multi. FD | Normal | Yes |
SCN1A
| c.5740_5742del | p.1914_1914del |
De novo
| LP |
172 | F/8y | DS | 5m | FS, aAb, Myo, FBTC | Multi. FD, GSW, GPSW | Normal | Yes |
SCN1A
| c.1327G > T | p.E443X |
De novo
| P |
Case code | Gender/age | Diagosis | Age of onset | Seizure types | EEG | Brain MRI/CT | Developmental delay | Gene | cDNA change | Protein change | Parental Origin | ACMG pathogenicity |
---|---|---|---|---|---|---|---|---|---|---|---|---|
55 | M/54d | OS | 1d | FoS, Tonic spasms | BS, FSW | Normal | Yes |
KCNQ2
| c.794C > T | p.A265V |
De novo
| P |
93 | M/40d | OS | 3d | Tonic spasms | BS | Normal | Yes |
SCN2A
| c.4712T > C | p.I1571T |
De novo
| LP |
90 | M/2y11m | OS-WS | 17d | Tonic spasms, Spa. | BS, Hypsarrhy. | Normal | Yes |
STXBP1
| c.364C > T | p.R122X | Unknown | P |
52 | F/1y8m | WS | 2m | Spa. | Multi. FD, Hypsarrhy. | Cerebral dysplasia | Yes |
ADSL
| c.253C > T | p.R85X | Maternal | LP |
ADSL
| c.71C > T | p.P24L | Paternal | UC | ||||||||
89 | F/1y11m | WS | 19d | FoS, Spa. | Multi. FD, Hypsarrhy. | Subdural hemorrhage | Yes |
KCNT1
| c.862G > A | p.G288S |
De novo
| P |
104 | F/2y10m | WS | 3m7d | Spa. | Hypsarrhy., Multi.FD | Normal | Yes |
CDKL5
| c.265delT | p.F89Lfs*24 |
De novo
| P |
151 | F/9m | WS | 3m | Spa. | Hypsarrhy., Multi. FD | Enlargement of the subarachnoid space | Yes |
STXBP1
| c.748C > T | p.Q250X |
De novo
| P |
29 | M/5y6m | Doose | 1y3m | Myo-At., Myo, aAb | Abnormal background theta, GSW, GPSW | Normal | No |
SYNGAP1
| c.274_277del | p.G92fs |
De novo
| P |
164 | F/6y | GLUT1-DS | 2y4m | GTCS | FSW, Multi. FD | Nonspecific (Hair loss leads to bald) | No |
SLC2A1
| c.296T > G | p.M99R |
De novo
| LP |
30 | F/4y4m | Rett | 3y2m | Fos (I), FBTC | Multi. FD | Normal | Yes |
MECP2
| c.799C > T | p.R267X |
De novo
| P |
32 | M/8y | TSC | 1y6m | FoS (I), FBTC | Multi. FD | Multi nodules | No |
TSC2
| c.2666C > T | p.A889V | Paternal | LP |
94 | F/9m | TSC (WS) | 3m | Spa. | Multi. FD, Hypsarrhy. | Multi nodules | Yes |
TSC2
| c.3412C > T | p.R1138X |
De novo
| P |
TSC2
| c.3598C > T | p.R1200W |
De novo
| P | ||||||||
98 | M/3y | TSC (WS) | 4m | Spa., aAb | Multi. FD, Hypsarrhy. | Nonspecific | Yes |
TSC2
| c.5079C > G | p.Y1693X | Paternal | LP |
TSC2
| c.5077delT | p.Y1693fs | Paternal | LP | ||||||||
7 | M/2y | UEE (EIEE13) | 6m | FoS (I), FBTC | Multi. FD | Enlargement of the subarachnoid space | Yes |
SCN8A
| c.4324G > A | p.E1442K | Paternal | LP |
IQSEC2
| c.4246_4247insG | p.S1416fs |
De novo
| P | ||||||||
63 | M/4y | UEE (EIEE42) | 5m | FoS, GTCS | Multi. FD | Normal | Yes |
CACNA1A
| c.301G > C | p.E101Q |
De novo
| P |
66 | M/1y9m | UEE (EIEE13) | 4m | FBTC, FoS | Multi. FD | Enlargement of the subarachnoid space | Yes |
SCN8A
| c.5492G > A | p.R1831Q |
De novo
| P |
69 | F/2y1m | UEE (EIEE9) | 1y3m | FBTC, C, T | Multi. FD | Normal | Yes |
PCDH19
| c.2849-1G > − | splicing | Unknown | LP |
157 | F/2y | UEE (EIEE43) | 2m | C, FoS (I) | FSW | Normal | Yes |
GABRB3
| c.761C > T | p.S254F |
De novo
| P |
160 | M/6y | UEE (EIEE19) | 6m | FoS (I), GTCS | FSW | Normal | Yes |
GABRA1
| c.641G > A | p.R214H |
De novo
| P |
54 | F/7y | UEE (EEOC) | 4y2m | SE, GTCS, FoS (I) | Mult. FD | Normal | Yes |
CHD2
| c.3640G > T | p.G1214X |
De novo
| P |
40 | F/2y11m | UE | 4m | FoS | FSW | Normal | No |
VRK2
| c.C256 + 1G > A | splicing | Unknown | LP |
44 | F/5y6m | UE | 4y | FoS (automatisms, emotional) | Multi. FD | Nodules in internal side of left anterior limb of internal capsule; caput of caudate nucleus or heterotopic gray matter | Yes |
ATP1A2
| c.1097G > T | p.G366V |
De novo
| LP |
68 | M/6y | UE | 4y | FoS (A) | FSW | Normal | No |
TSC1
| c.2768_2769insC | p.L924Ffs*26 |
De novo
| P |
79 | M/3y | UE | 1y2m | FoS (I), FBTC | Multi. FD | Normal | Yes |
SLC9A6
| c.582_595del | p.Y194fs |
De novo
| P |
Clinical benefits | Effects (Case details) | |
---|---|---|
Diagnosis | SLC2A1 (GLUT1-DS) | Definitive diagnosis (Case 164) |
SCN1A (DS) | Definitive diagnosis (Case 13, 38, 65, 115, 140) | |
TSC2 (TSC) | Definitive diagnosis (Case 94, 98) | |
Management implications | SLC2A1, using KD | Controlled (Case 164, KD) |
SCN1A, stopping OXC | Remitted (Case 13, VPA, TPM,10–20 / month) | |
SCN1A, avoiding OXC, CBZ, and LTG | Remitted (Case 23, VPA, TPM, seizure-free for 5 months; Case 26, LEV, TPM, CZP, seizure-free for 6 months; Case 149, VPA, TPM, LEV, CZP, seizure-free for 4 months; Case 172, VPA, TPM, CZP, seizure-free for 1 year) | |
Uncontrolled (Case 35, 38, 53, 56, 65, 115, 124, 130, 140, 148, 162) | ||
TSC2, using rapamune | Remitted (Case 32, seizure-free for 7 months) | |
Long-term follow up | TSC1 (risk of TSC) | Case 68 |
Reproductive planning | Suggesting the family conduct genetic counseling | TSC2 (Case 32, 98), SCN8A (Case 7), SCN1A (Case 149), ADSL (Case 52) |