The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; 7 of the 29 sources its claims cite were checked for support.
SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures
Open accessAbstract
OBJECTIVE: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. METHODS: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. RESULTS: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. CONCLUSIONS: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control.
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30 Own result · 12 Own interpretation · 8 No full text of the sources · 5 No basis given · 3 Partly supported · 3 Sources not found · 1 Supported · 1 Supported so far · 1 Not checked yet · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Seven patients with SCN2A mutations had EIMFS, constituting 26% (7/27) of our total cohort of patients with EIMFS and rendering SCN2A the second most commonly mutated gene for EIMFS, after KCNT1.25,26”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Supportedcites [25] 25. Barcia G, Fleming MR, Deligniere A, et al. De novo gain- of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012;44: 1255-1259. source
The cited paper’s Abstract reports KCNT1 mutations in 6 of 12 patients with malignant migrating partial seizures of infancy and calls KCNT1 a major disease gene. That supports the citation’s KCNT1 background point; the SCN2A count and ranking in “our cohort” are the citing authors’ own findings, not findings attributed to this source. (LLM, conf=0.88)
- Partly supportedcites [26] 26. McTague A, Appleton R, Avula S, et al. Migrating partial seizures of infancy: expansion of the electroclinical, radio- logical and pathological disease spectrum. Brain 2013;136: 1578-1591. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) calls KCNT1 a likely major gene for migrating partial seizures of infancy, and Other investigations reports KCNT1 mutations in two patients. The paper does not establish that SCN2A was the second most commonly mutated gene or report the citing authors’ seven SCN2A cases among 27 patients. (LLM, conf=0.86)
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 7 died in the context of refractory seizures and extreme autonomic dysfunction at 22 months.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Weekly ECGs during this period showed no cardiac rhythm abnormality.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight had severe to profound developmental impairment.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Two patients showed a considerably better outcome than is usual for EIMFS.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All 10 patients with scans available for review had abnormalities on brain MRI (table, figure 3).”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“White matter T2 hyperintensities were seen on only one scan in 3 of 4 patients who had sequential imaging: on the first scan (10-60 days) but not on follow-up imaging (20 days to 22 months) in 2, and on the second scan (81 days) but not the first (9 days) in the other.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Multifocal interictal epileptiform discharges were seen in all.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 25
- Probably not a substantial claim. 10
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Seven patients with SCN2A mutations had EIMFS, constituting 26% (7/27) of our total cohort of patients with EIMFS and rendering SCN2A the second most commonly mutated gene for EIMFS, after KCNT1.25,26”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Supportedcites [25] 25. Barcia G, Fleming MR, Deligniere A, et al. De novo gain- of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012;44: 1255-1259. source
The citation follows “after KCNT1,” while the seven SCN2A cases and 7/27 figure are explicitly from the citing authors’ own cohort. The source’s Abstract identifies KCNT1 mutations in 6 of 12 patients with malignant migrating partial seizures of infancy, supporting the KCNT1 association for which it is cited. No page number is available in our copy. (LLM, conf=0.88)
- Could not verifycites [26] 26. McTague A, Appleton R, Avula S, et al. Migrating partial seizures of infancy: expansion of the electroclinical, radio- logical and pathological disease spectrum. Brain 2013;136: 1578-1591. sourceExperimental — accuracy not yet measured
The source’s Other investigations section reports two patients with KCNT1 variants in its MPSI cohort, while the Discussion describes earlier SCN2A screening with negative findings. Neither passage addresses the citing authors’ cohort of 27 or reports seven patients with SCN2A mutations, so the 7/27 figure cannot be verified from this paper. Page numbers are unavailable in our copy. (LLM, conf=0.76)
plaincorrelationaln = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Phenotypic features that distinguish SCN2A-associated EIMFS from KCNT1-associated EIMFS 25 include severe movement disorders and response to phenytoin in some patients.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Supportedcites [25] 25. Barcia G, Fleming MR, Deligniere A, et al. De novo gain- of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012;44: 1255-1259. source
Citation 25 appears immediately after “KCNT1-associated EIMFS,” identifying that condition rather than attributing the subsequent comparison to this source. The Abstract (page unavailable) reports KCNT1 mutations in patients with malignant migrating partial seizures of infancy, supporting that identification. (LLM, conf=0.91)
plaincorrelationaln = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“While the observation of seizure improvement is based only on retrospective clinical review, this finding reinforces previous observations of drug response: withdrawal of phenytoin provoking status epilepticus in one case, status treated with fosphenytoin in another, 2 seizure-free on lamotrigine, and one with seizure control on lidocaine.6,12,14”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Supportedcites [6] 6. Ogiwara I, Ito K, Sawaishi Y, et al. De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies. Neurology 2009;73:1046-1053. source
The citation supports the previous drug-response observation, not the citing authors’ qualification about retrospective clinical review. In the Patients section (page unavailable), the source reports that a patient with neonatal epileptic encephalopathy was partially rescued using lidocaine. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [12] 12. Nakamura K, Kato M, Osaka H, et al. Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome. Neurology 2013;81:992-998. source
- Not checked — no full text of the sourcecites [14] 14. Dhamija R, Wirrell E, Falcao G, et al. Novel de novo SCN2A mutation in a child with migrating focal seizures of infancy. Pediatr Neurol 2013;49:486-488. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While Dravet syndrome is differentiated by age at onset and seizure types, rare cases of EIMFS due to SCN1A mutations are described.26,36,38”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Partly supportedcites [26] 26. McTague A, Appleton R, Avula S, et al. Migrating partial seizures of infancy: expansion of the electroclinical, radio- logical and pathological disease spectrum. Brain 2013;136: 1578-1591. sourceExperimental — accuracy not yet measured
The Discussion reports three MPSI (EIMFS) cases with SCN1A abnormalities among 22 tested, supporting the claim that rare cases have been described. Our copy does not discuss how Dravet syndrome is differentiated by age at onset or seizure type, so that part is not supported by this source. Page numbers are not available in the indexed passages. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [36] 36. Mulley JC, Scheffer IE, Petrou S, et al. SCN1A mutations and epilepsy. Hum Mutat 2005;25:535-542. source
- Not checked — no full text of the sourcecites [38] 38. Brunklaus A, Ellis R, Reavey E, et al. Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. Brain 2012;135:2329-2336. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Histopathologic examination of the brain revealed reduced total brain weight, marked cortical dyslamination of temporal lobes, cortical gliosis most prominent in the temporal lobes and around the interhemispheric fissure, and bilateral hippocampal CA1 neuronal loss, gliosis, and astrocytosis.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sudden unexpected death occurred in patient 3 and patient 12 in sleep at age 21 months and 20 years, respectively.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
plaindirectn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 3 had commenced phenytoin a month before death, with a marked seizure improvement.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MRI brain scans were reported as normal in patients 5 and 10.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In contrast to previous series, only 2 of our cases had Ohtahara syndrome and none had West syndrome, as hypsarrhythmia was not present in those with infantile spasms.6,8,[10][11][12][13]15”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not matchedcites 6,8,[10][11][12][13]15
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“Delayed myelination was noted in 2 patients, reduced white matter volume in 4, T1 hyperintensities in the basal ganglia in 3, diffusion restriction in the cerebellum in one, and moderate cerebellar and cerebral atrophy in one.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
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“Postmortem analysis in patient 3 revealed the cause of death to be pneumonia.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
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“Eight patients had T2 hyperintensities, in white matter in 8, basal ganglia in 5, thalamus in 4, and brainstem in 5.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
plainn = 8- Asserted: passes — The authors put it forward as true.
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“The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
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“Six patients had elongated superior temporal sulci, 4 had small anterior temporal lobes, one had small frontal lobes, and 2 had underopercularization of the sylvian fissure.”
§ A major cause of epilepsy of infancy with migrating focal seizures > Development.
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“Our patients presented at a median of 2 days with multiple types of brief focal seizures that cluster, reaching maximal frequency of multiple hourly seizures within 3 months of onset.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Episodes consistent with infantile spasms or tonic seizures occurred in some, sometimes without an EEG correlate, raising the possibility that these are paroxysmal movement disorders mimicking seizures in some patients.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
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“Although mutations identified in patients with BFNIS and SCN2A encephalopathy show different inheritance patterns and Grantham scores, 37 and no BFNIS-associated mutations have been found in patients with SCN2A encephalopathy, mutations are found throughout the gene (figure 1) and affect both transmembrane domains and linker regions in both phenotypes.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [37] 37. Brunklaus A, Ellis R, Reavey E, et al. Genotype phenotype associations across the voltage-gated sodium channel fam- ily. J Med Genet 2014;51:650-658. source
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In the paper
“Phenytoin did not, however, significantly improve development in the patients with seizure improvement and was not associated with clear seizure improvement in all patients, although seizures were not exacerbated.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Movement disorders, axial hypotonia, and gastrointestinal problems are frequent.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1”
§ A major cause of epilepsy of infancy with migrating focal seizures > Abstract Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies.Herein, we define the phenotypic spectrum of SCN2A encephalopathy.Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.Results: Patients were aged 0.7 to 22 years; 3 were deceased.Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset.Multifocal interictal epileptiform discharges were seen in all.Three of 12 patients had infantile spasms.The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment.Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms.Mutations arose de novo in 11 patients; paternal DNA was unavailable in one.Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome.Sodium channel blockers, particularly phenytoin, may improve seizure control. SCN2A encodes the major a subunit (Na v 1.2) of voltage-gated sodium channels in excitatory neurons. 1 We first identified inherited mutations in SCN2A in the self-limited autosomal dominant epilepsy syndrome, benign familial neonatal infantile seizures (BFNIS).2,3 De novo SCN2A mutations have increasingly been recognized to cause severe disorders, reported in 39 patients with epileptic encephalopathies (EEs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5 patients with intellectual disability without epilepsy.[21][22][23] Cohorts with prototypic EEs, Ohtahara and West syndrome, due to SCN2A mutations are described.To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS), which begins before 6 months of age and is characterized by multiple types of focal seizures that "migrate" from one hemisphere to another, usually with severe developmental impairment.
What the sources say
- Not checked — no full text of the sourcecites [1] 1. Oliva M, Berkovic SF, Petrou S. Sodium channels and the neurobiology of epilepsy. Epilepsia 2012;53:1849-1859. source
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In the paper
“To date, there has only been a single case of SCN2A causing EIMFS who also had a paternally inherited 15q11.2deletion.14”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [14] 14. Dhamija R, Wirrell E, Falcao G, et al. Novel de novo SCN2A mutation in a child with migrating focal seizures of infancy. Pediatr Neurol 2013;49:486-488. source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Sudden unexpected death in epilepsy (SUDEP) is recognized in other sodium channelopathies including Dravet syndrome and 2 cases of SCN8A encephalopathy.27,30,31”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Larsen J, Carvill GL, Gardella E, et al. The phenotypic spectrum of SCN8A encephalopathy. Neurology 2015;84: 480-489. source
- Not checked — no full text of the sourcecites [30] 30. Veeramah KR, O'Brien JE, Meisler MH, et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epilep- tic encephalopathy and SUDEP. Am J Hum Genet 2012; 90:502-510. source
- Not checked — no full text of the sourcecites [31] 31. Sakauchi M, Oguni H, Kato I, et al. Retrospective multi- institutional study of the prevalence of early death in Dravet syndrome. Epilepsia 2011;52:1144-1149. source
plaincorrelationaln = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“SCN8A encephalopathy can present with early-onset EE and responds to sodium channel blockers 27,30,39 in contradistinction to SCN1A diseases.38,40”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Larsen J, Carvill GL, Gardella E, et al. The phenotypic spectrum of SCN8A encephalopathy. Neurology 2015;84: 480-489. source
- Not checked — no full text of the sourcecites [30] 30. Veeramah KR, O'Brien JE, Meisler MH, et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epilep- tic encephalopathy and SUDEP. Am J Hum Genet 2012; 90:502-510. source
- Not checked — no full text of the sourcecites [39] 39. Ohba C, Kato M, Takahashi S, et al. Early onset epileptic encephalopathy caused by de novo SCN8A mutations. Epilepsia 2014;55:994-1000. source
- Not checked — no full text of the sourcecites [38] 38. Brunklaus A, Ellis R, Reavey E, et al. Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. Brain 2012;135:2329-2336. source
- Not checked — no full text of the sourcecites [40] 40. Guerrini R, Dravet C, Genton P, et al. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia 1998;39:508-512. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Our analysis suggests that patients fall into 3 phenotypic groups: a severe neonatalinfantile phenotype, an intermediate neonatal-infantile phenotype, and a childhood phenotype (figure 4).”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
hedgedn = 46- Asserted: passes — The authors put it forward as true.
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In the paper
“The expanded phenotypic spectrum of SCN2A mutations parallels that seen with KCNQ2 and SCN1A and may be broader than currently appreciated.[34][35][36]”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not matchedcites [34][35][36]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“There are now 46 patients reported with SCN2A encephalopathy (12 here, 39 reported; 5 patients reported twice). [4][5]][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
plainn = 46- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“SCN2A is an important cause of EE with an emerging distinctive picture, particularly for the severe phenotype.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The movement disorders in SCN2A encephalopathy overlap those seen in other conditions such as SCN8A encephalopathy, 27 in contrast to other conditions such as STXBP1 encephalopathy, in which a distinctive movement disorder, a”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [27] 27. Larsen J, Carvill GL, Gardella E, et al. The phenotypic spectrum of SCN8A encephalopathy. Neurology 2015;84: 480-489. source
- Not checked — no full text of the sourcecites [28] 28. Kim YO, Korff CM, Villaluz MMG, et al. Head stereo- typies in STXBP1 encephalopathy. Dev Med Child Neu- rol 2013;55:769-772. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This mortality rate is comparable to Dravet syndrome, another sodium channelopathy due to SCN1A mutations, which is approximately 15% by age 20 years.29”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [29] 29. Roger J, Bureau M, Dravet C, Genton P. Epileptic Syn- dromes in Infancy, Childhood, and Adolescence. Mon- trouge, France: John Libbey Eurotext; 2005.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, patients 3 and 10, who share the same mutation, show phenotypic variability suggesting that modifier genes have a role.”
§ A major cause of epilepsy of infancy with migrating focal seizures > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper relies on this without support.
Only single cases of other syndromes, including EIMFS, have been reported in association with SCN2A mutations.
“To date, only single cases of other syndromes are reported, including epilepsy of infancy with migrating focal seizures (EIMFS)”
The paper relies on this without support.
The 34 other reported cases of SCN2A encephalopathy are sufficiently comparable to the authors' 12 cases to be combined in a phenotype review.
“Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes”
Self-check
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Each contradiction between two passages listed here was confirmed by an independent check.
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In the paper
§ A major cause of epilepsy of infancy with migrating focal seizures > RESULTS
“Five mutations (patients 2, 3, 4, 9, 11) have been reported with limited clinical information.9 Seven patients have novel mutations.”
§ A major cause of epilepsy of infancy with migrating focal seizures > RESULTS
“A recurrent mutation (p.Arg1882Gln) occurred in patients 3 and 10.”
Citations
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De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084
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A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns
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Self-citationLamotrigine and Seizure Aggravation in Severe Myoclonic Epilepsy
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Cited by
Sorted by citations
Zuberi, S. M., Wirrell, E., Yozawitz, E., Wilmshurst, J. M., Specchio, N., Riney, K., Pressler, R., Auvin, S., Samia, P., Hirsch, E., et al. (2022) · Epilepsia · doi:10.1111/epi.17239 · Cited by 934
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Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders
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“Howell et al. (2015) reported the appearance of myoclonus with vigaba-trin and lamotrigine in one child.”
BackgroundInfluentialThe genetic landscape of the epileptic encephalopathies of infancy and childhood
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“While most children with SCN2A variants fit into one of these three categories, there are some exceptions, including epileptic encephalopathy with choreoathetoid movements [26,27], BISs with late-onset episodic ataxia [28–31], childhood-onset epileptic encephalopathy [32], and schizophrenia [33,34].”
BackgroundIon Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies
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Dravet syndrome and its mimics: Beyond SCN 1A
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Developmental and epileptic encephalopathies: what we do and do not know
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The phenotype of SCN8A developmental and epileptic encephalopathy
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Self-citationClinical and molecular characterization of KCNT1 -related severe early-onset epilepsy
McTague, A., Nair, U., Malhotra, S., Meyer, E., Trump, N., Gazina, E. V., Papandreou, A., Ngoh, A. S. F., Ackermann, S., Ambegaonkar, G., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004762 · Cited by 143
Self-citationThe Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures
Burgess, R., Wang, S., McTague, A., Boysen, K. E., Yang, X., Zeng, Q., Myers, K. A., Rochtus, A., Trivisano, M., Gill, D., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25619 · Cited by 141
“For patients or parents, when evidence of mosaicism was observed from WES or MIP data, or suspected based on PCR, additional methods were used for confirmation, as published.(7,9) Droplet digital PCR was used to confirm that the variant in the mother of Patients 11 and 12 was definitively heterozygous and not mosaic (…”
BackgroundMethodInfluentialSelf-citationEpilepsy-Related Voltage-Gated Sodium Channelopathies: A Review
Menezes, L. F. S., Júnior, E. F. S., Tibery, D. V., Carneiro, L. D. A., & Schwartz, E. F. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01276 · Cited by 143
“…seizures Atonic seizures Myoclonic-atonic seizures Tonic seizures Atypical absences (Wolff et al., 2017) N976K DII Missense EE Focal seizures (Howell et al., 2015) S987I DII Missense EIEE Focal and tonic seizures (Trump et al., 2016) G999L DII-DIII Missense Infantile epilepsy Diffuse…”
BackgroundInfluentialSCN8A encephalopathy: Research progress and prospects
Meisler, M. H., Helman, G., Hammer, M. F., Fureman, B. E., Gaillard, W. D., Goldin, A. L., Hirose, S., Ishii, A., Kroner, B. L., Lossin, C., et al. (2016) · Epilepsia · doi:10.1111/epi.13422 · Cited by 135
Self-citationRapid and safe response to low‐dose carbamazepine in neonatal epilepsy
Sands, T. T., Balestri, M., Bellini, G., Mulkey, S. B., Danhaive, O., Bakken, E. H., Taglialatela, M., Oldham, M. S., Vigevano, F., Holmes, G. L., et al. (2016) · Epilepsia · doi:10.1111/epi.13596 · Cited by 135
Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies
Møller, R. S., Larsen, L. H. G., Johannesen, K. M., Talvik, I., Talvik, T., Vaher, U., Miranda, M. J., Farooq, M., Nielsen, J. E. K., Svendsen, L. L., et al. (2016) · Molecular Syndromology · doi:10.1159/000448369 · Cited by 135
Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype
Sadleir, L. G., Mountier, E. I., Gill, D., Davis, S., Joshi, C., DeVile, C., Kurian, M. A., Study, F. T. D., Mandelstam, S., Wirrell, E., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004331 · Cited by 131
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Self-citationThe phenotypic spectrum of SCN2A-related epilepsy
Reynolds, C., King, M. D., & Gorman, K. M. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.12.016 · Cited by 124
KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects
Lim, C. X., Ricos, M. G., Dibbens, L. M., & Heron, S. E. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103508 · Cited by 121
A population‐based cost‐effectiveness study of early genetic testing in severe epilepsies of infancy
Howell, K. B., Eggers, S., Dalziel, K., Riseley, J., Mandelstam, S., Myers, C. T., McMahon, J. M., Schneider, A., Carvill, G. L., Mefford, H. C., et al. (2018) · Epilepsia · doi:10.1111/epi.14087 · Cited by 114
Self-citationUnderstanding Genotypes and Phenotypes in Epileptic Encephalopathies
Helbig, I., & Tayoun, A. N. A. (2016) · Molecular Syndromology · doi:10.1159/000448530 · Cited by 117
Identifying mutations in epilepsy genes: Impact on treatment selection
Perucca, P., & Perucca, E. (2019) · Epilepsy Research · doi:10.1016/j.eplepsyres.2019.03.001 · Cited by 120
von Spiczak, S., Helbig, K. L., Shinde, D. N., Huether, R., Pendziwiat, M., Lourenço, C. M., Nuñes, M. E., Sarco, D. P., Kaplan, R. A., Dlugos, D., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004152 · Cited by 112
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Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells
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Phenotypic and genetic spectrum of SCN 8A‐related disorders, treatment options, and outcomes
Gardella, E., & Møller, R. S. (2019) · Epilepsia · doi:10.1111/epi.16319 · Cited by 104
DominantKCNA2mutation causes episodic ataxia and pharmacoresponsive epilepsy
Corbett, M. A., Bellows, S. T., Li, M., Carroll, R., Micallef, S., Carvill, G. L., Myers, C. T., Howell, K. B., Maljevic, S., Lerche, H., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003309 · Cited by 99
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Self-citationGenomic analysis identifies masqueraders of full‐term cerebral palsy
Takezawa, Y., Kikuchi, A., Haginoya, K., Niihori, T., Numata‐Uematsu, Y., Inui, T., Yamamura‐Suzuki, S., Miyabayashi, T., Anzai, M., Suzuki‐Muromoto, S., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.551 · Cited by 98
“Both genes have not been reported to cause spastic CP; however, the spasticity of patients has been reported previously.(32,41) The patients with other CP subtypes, including ataxic type and dyskinetic type, showed no tendency toward spastic diplegia.”
BackgroundImpact of predictive, preventive and precision medicine strategies in epilepsy
Nabbout, R., & Kuchenbuch, M. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0409-4 · Cited by 101
Berecki, G., Howell, K. B., Deerasooriya, Y. H., Cilio, M. R., Oliva, M., Kaplan, D. I., Scheffer, I. E., Berkovic, S. F., & Petrou, S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800077115 · Cited by 85
“Particularly, there is a group of patients with seizure onset in the early infantile period (“early-onset”) in whom sodium-channel blockers, such as phenytoin and carbamazepine, may improve seizures, and a group with seizure onset later in infancy (“later-onset” group, >3 mo) in whom sodium-channel blockers are rarely…”
BackgroundSelf-citationMao, X. O., Bruneau, N., Gao, Q., Becq, H., Jia, Z., Xi, H., Shu, L., Wang, H., Szepetowski, P., & Aniksztejn, L. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00001 · Cited by 86
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Secondary Coenzyme Q 10 Deficiencies in Oxidative Phosphorylation (OXPHOS) and Non-OXPHOS Disorders
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Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy
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Precision medicine in genetic epilepsies: break of dawn?
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The severe epilepsy syndromes of infancy: A population‐based study
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Self-citationRecent advances in gene therapy for neurodevelopmental disorders with epilepsy
Turner, T. J., Zourray, C., Schorge, S., & Lignani, G. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15168 · Cited by 71
“However, while patients with SCN2A encephalopathy do display various types of focal seizures, absence-like seizures are not commonly reported, suggesting a possible species-specific effect (Hedrich et al. 2019; Howell et al. 2015).”
BackgroundSCN3A deficiency associated with increased seizure susceptibility
Lamar, T., Vanoye, C. G., Calhoun, J. D., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M. T., Escayg, A., & Kearney, J. A. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.02.006 · Cited by 71
“Mutations in these VGSCs are responsible for an increasing number of epilepsy syndromes (Escayg et al., 2000; Estacion et al., 2014; Fung et al., 2015; Howell et al., 2015; Schwarz et al., 2016; Sugawara et al., 2001; Surovy et al., 2016).”
BackgroundComputational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders
Crawford, K., Xian, J., Helbig, K. L., Galer, P. D., Parthasarathy, S., Lewis‐Smith, D., Kaufman, M. C., Fitch, E., Ganesan, S., O’Brien, M., et al. (2021) · Genetics in Medicine · doi:10.1038/s41436-021-01120-1 · Cited by 58
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Preventing cognitive impairment in children with epilepsy
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The expanding spectrum of movement disorders in genetic epilepsies
Papandreou, A., Danti, F. R., Spaull, R., Leuzzi, V., McTague, A., & Kurian, M. A. (2019) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14407 · Cited by 65
“Patients occasionally also manifest oculogyric crises, episodic ataxia, and prominent stereotypies in childhood.(29,30) SCN8A, encoding another sodium channel subunit, has recently emerged as an important cause of DEE, implicated in West syndrome, LGS, and Dravet syndrome, as well as benign familial neonatal-infantile…”
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“SUDEP have been reported in one patient with ADNFLE related to KCNT1 mutations and in 11 patients with EIMFS out of 152 (7%) without known mutations or with mutations in other genes (Gross-Tsur et al., 2004; Hmaimess et al., 2006; Freilich et al., 2011; Fasulo et al., 2012; McTague et al., 2013; Milh et al., 2013; How…”
BackgroundMishra, V., Karumuri, B. K., Gautier, N. M., Liu, R., Hutson, T. N., Vanhoof‐Villalba, S. L., VLACHOS, I. K., Iasemidis, L. D., & Glasscock, E. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx104 · Cited by 61
Voltage-gated sodium channels in excitable cells as drug targets
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“[34] and other less well delineated forms of epileptic encephalopathies [35–37].”
BackgroundRecent advances in treatment of epilepsy-related sodium channelopathies
Musto, E., Gardella, E., & Møller, R. S. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.12.009 · Cited by 59
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Autism spectrum disorder and epileptic encephalopathy: common causes, many questions
Srivastava, S., & Şahin, M. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9202-0 · Cited by 55
“He developed seizures at 3 years of age, around the same time as his diagnosis of “autism” [92].”
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Dendritic Integration Dysfunction in Neurodevelopmental Disorders
Nelson, A. D., & Bender, K. J. (2021) · Developmental Neuroscience · doi:10.1159/000516657 · Cited by 54
Alternative splicing potentiates dysfunction of early-onset epileptic encephalopathy SCN2A variants
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Stiripentol in the Management of Epilepsy
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Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and dysmorphic features
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Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures
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Self-citationModels for discovery of targeted therapy in genetic epileptic encephalopathies
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“(2017) 143, 30--48 Dravet-like syndrome as well as unclassified epileptic encephalopathy (Howell et al. 2015; Wolff et al. 2017).”
BackgroundResurgent and Gating Pore Currents Induced by De Novo SCN2A Epilepsy Mutations
Mason, E. R., Wu, F., Patel, R. R., Xiao, Y., Cannon, S. C., & Cummins, T. (2019) · eNeuro · doi:10.1523/eneuro.0141-19.2019 · Cited by 46
Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders
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Regulatory genes and pathways disrupted in autism spectrum disorders
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“SCN2A mutation has been shown to be associatedwith autism (12, 13), developmental delays (14) and infantile seizure disorders (15).”
BackgroundLacosamide for SCN2A ‐related intractable neonatal and infantile seizures
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Benign and severe early-life seizures: a round in the first year of life
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“The same authors [74] report in five patients, an improved seizure control with sodium channel blockers using high dosage of phenytoin.”
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Hoelz, H., Herdl, C., Gerstl, L., Tacke, M., Vill, K., von Stülpnagel-Steinbeis, C., Rost, I., Hoertnagel, K., Abicht, A., Hollizeck, S., et al. (2019) · Clinical EEG and Neuroscience · doi:10.1177/1550059419876518 · Cited by 41
Epilepsy and brain channelopathies from infancy to adulthood
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Neonatal Seizures: An Overview of Genetic Causes and Treatment Options
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Self-citationRelationship of electrophysiological dysfunction and clinical severity inSCN2A-related epilepsies
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De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis
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Genetic variations associated with pharmacoresistant epilepsy (Review)
C�rdenas‐Rodr�guez, N., Carmona‐Aparicio, L., P�rez‐Lozano, D., Ortega-Cuéllar, D., G�mez‐Manzo, S., & Ignacio‐Mejía, I. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.10999 · Cited by 36
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Functional correlates of clinical phenotype and severity in recurrent SCN2A variants
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Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine
Foster, L. A., Johnson, M. R., MacDonald, J. T., Karachunski, P. I., Henry, T. R., Nascene, D. R., Moran, B. P., & Raymond, G. V. (2017) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2016.10.008 · Cited by 34
Poisson, K. E., Wong, M., Lee, C., & Cilio, M. R. (2019) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2019.12.024 · Cited by 35
Modeling epileptic spasms during infancy: Are we heading for the treatment yet?
Velı́šek, L., & Velı́šková, J. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107578 · Cited by 31
SUDEP risk and autonomic dysfunction in genetic epilepsies
Sahly, A. N., Shevell, M. I., Sadleir, L. G., & Myers, K. A. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102907 · Cited by 32
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“6 and 1.2 are associated with epilepsy (Veeramah et al., 2012; Howell et al., 2015).”
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Self-citationThe influence of sodium on pathophysiology of multiple sclerosis
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“2 SCN2A CNS, PNS CBH, dementia [70], epilepsy [73, 74], autism [74]”
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“However, no clear genotype– phenotype correlation was identified to explain phenotypic variations [6].”
Metadata
- Authors
- Howell, K. B., McMahon, J. M., Carvill, G. L., Tambunan, D., Mackay, M. T., Rodriguez-Casero, V., Webster, R., Clark, D., Freeman, J. L., Calvert, S., Olson, H. E., Mandelstam, S., Poduri, A., Mefford, H. C., Harvey, A. S., & Scheffer, I. E.
- Affiliations
- Boston Children's Hospital (US)
- From the Departments of Neurology (K.B.H., M.T.M., V.R.-C., J.L.F., A.S.H., I.E.S.) and Radiology (S.M.), The Royal Children's Hospital, Melbourne; Department of Paediatrics (K.B.H., M.T.M., S.M., A.S.H., I.E.S.), The University of Melbourne; Murdoch Childrens Research Institute (K.B.H., M.T.M., J.L.F., A.S.H.), Melbourne; Epilepsy Research Centre (J.M.M., I.E.S.), Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia; Division of Genetic Medicine (G.L.C., H.C.M.),...
- ORCID
- Venue
- Neurology
- Published
- 2015-09-15
- Volume
- 85
- Issue
- 11
- Pages
- 958-966
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4567464
- OpenAlex
- W1798842141
- Cited by
- 255
- References
- 41
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 14 · 2023: 18 · 2022: 17 · 2021: 33 · 2020: 28 · 2019: 30 · 2018: 23 · 2017: 34 · 2016: 20 · 2015: 1
- FWCI
- 21.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Burroughs Wellcome Fund
- GlaxoSmithKline
- Jack Brockhoff Foundation
- University of Melbourne
- Epilepsy Society
- Shepherd Foundation
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- Health Research Council of New Zealand
- National Institute of Neurological Disorders and Stroke
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083091)
- Cilag
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- SCN2A, sodium channel mutations, epileptic encephalopathy, infantile-onset epilepsy, epilepsy of infancy with migrating focal seizures, Ohtahara syndrome, infantile spasms, phenytoin, sodium channel blockers, developmental outcomes, movement disorders, hypotonia, seizure clusters, interictal epileptiform discharges
- MeSH terms
- Adolescent, Brain Diseases, Child, Child, Preschool, Electroencephalography, Epilepsies, Partial, Female, Humans, Infant, Male, Mutation, Phenotype, Seizures, Spasms, Infantile, Genetic Predisposition to Disease, Young Adult, NAV1.2 Voltage-Gated Sodium Channel
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