| |
Proband 1/Fam.1 |
Proband 2/Fam.2 |
Proband 3/Fam.3 |
Proband 4/Fam.4 |
Proband 5/Fam.5 |
| Genotype (gene, mutation) |
SCN1A c.[2134C>T;3521C>G];[=] p.[Trp1174Ser];[=] |
SCN1Ac.[2134C>T;3521C>G];[=] p.[Arg712*;Trp1174Ser];[=] |
SCN1A c.[3733C>T];[3521C>G] p.[Arg1245*];[Trp1174Ser] |
SCN1A c.[2134C>T;3521C>G];[=] p.[Trp1174Ser];[=] ARX c.[1449-43_1448del];[0] p.[?];[0] |
SCN1A c.[2134C>T;3521C>G];[=] p.[Trp1174Ser];[=] PCDH19 c.[463G>T];[=] p.[Asp155Tyr ];[=] |
| Gender |
F |
M |
F |
M |
F |
| Age at investigation |
6 y. |
17 y. |
11 y. |
21y. |
10 y. |
| Diagnosis |
GEFS+ |
Dravet syndrome |
Dravet syndrome |
Atypical West syndrome |
EFMR |
| Family history (Pedigrees Figure 1) |
intellectual impairment andmigrainein mother; epilepsy in sister; intellectual impairment in sister and brother |
migraine in mother and maternal grandmother |
intellectual impairment and epilepsy in mother |
emotional disturbances in mother |
migraine in father, father’s sister and grandfather |
| Age at onset |
3 mo. |
8 mo. |
7 mo. |
3 mo. |
7 mo. |
| First seizure |
tonic-clonic, febrile seizures |
hemiclonic during infection |
febrile seizures (type unknown) |
vaccination, loss of consciousness |
tonic-clonic during infection |
| Subsequent seizure types |
tonic-clonic, hemiclonic, tonic with cyanosis |
tonic-clonic, hemiclonic, myoclonic, complex seizures, tonic |
tonic-clonic, hemiclonic, tonic with cyanosis, absence, myoclonic |
infantile spasms, atonic, hemiclonic, myoclonic, tonic-clonic |
tonic with apnoea, tonic-clonic |
| Seizure clusters |
Yes |
Yes |
Yes |
Yes |
Yes |
| Status epilepticus |
No |
Yes |
Yes |
Yes |
Yes |
| Acute encephalopathy |
No |
No |
No |
Yes |
Yes |
| Seizure induced by |
- |
CBZ, LTG, VGB, TPM, GBP |
CLN, VGB, OXC, LTG |
VGB, TPM |
LTG, VGB |
| Improvement with |
VPA |
VPA, CLB |
LEV |
VPA, BZD, LEV |
STR |
| Remission age |
5 mo. |
no |
no |
12 y. |
8 y. |
| EEG |
focal changes and then normal |
generalized changes, slowing background |
generalized and focal changes, slowing background |
hypsarrythmia, then generalized changes |
focal and generalized changes, then normal |
| Neurological exam |
normal |
ataxia, tetraparesis |
ataxia |
tetraparesis |
ataxia |
| Development |
normal at onset; intellectual impairment at the age of 6 years |
normal at onset; regression from the age of 2 years; severe intellectual impairment now |
normal at onset; significant regression and autism at the age of 2 years |
normal at onset; delayed in the first year of life; acute regression related to encephalopathy at the age of 6 years |
normal at onset; start delayed in the second year of life; mild intellectual impairment now |
| Comments |
Intellectual impairment is not related to SCN1A mutation; caused probably by other familial factors |
Severe disease course was partially related to ineffective treatment, the presence of the SCN1A p.Trp1174Ser has no influence of phenotype as is monoallelic and localised 3’ to premature STOP codon |
Severe phenotype with fast progressing intellectual impairment and autism might be related to coexistence of two mutations in SCN1A gene |
Hemiclonic seizures triggered by fever and acute encephalopathy episode and treatment response might be related to additional mutation with SCN1A |
Severe EFMR phenotype, treatment response and appearance of acute encephalopathy might be related to additional mutation in SCN1A |
