Raras
Buscar doenças, sintomas, genes...
Convulsões focais migratórias malignas da infância
ORPHA:293181CID-10 · G40.0CID-11 · 8A61.12PCDT · SUSDOENÇA RARA

Uma forma grave muito rara de epilepsia com mau prognóstico que geralmente começa algumas semanas após o nascimento. A atividade convulsiva pode aparecer em vários locais do cérebro ou migrar de uma região para outra durante um episódio. Isso resulta em grave atraso no desenvolvimento.

Mantido por Agente Raras·Colaborar como especialista →

Introdução

O que você precisa saber de cara

📋

Uma forma grave muito rara de epilepsia com mau prognóstico que geralmente começa algumas semanas após o nascimento. A atividade convulsiva pode aparecer em vários locais do cérebro ou migrar de uma região para outra durante um episódio. Isso resulta em grave atraso no desenvolvimento.

Publicações científicas
124 artigos
Último publicado: 2026 Apr 14

Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
<1 / 1 000 000
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
0.0
Worldwide
Casos conhecidos
114
pacientes catalogados
Início
Infancy
+ neonatal
🏥
SUS: Cobertura parcialScore: 45%
PCDT disponívelCID-10: G40.0
🇧🇷Dados SUS / DATASUS
PROCEDIMENTOS SIGTAP (2)
0202010694
Sequenciamento completo do exoma (WES)genetic_test
0301070040
Atendimento em reabilitação — doenças rarasrehabilitation
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🧠
Neurológico
28 sintomas
👁️
Olhos
3 sintomas
📏
Crescimento
3 sintomas
❤️
Coração
2 sintomas
💪
Músculos
2 sintomas
🦴
Ossos e articulações
1 sintomas

+ 10 sintomas em outras categorias

Características mais comuns

90%prev.
Déficit motor funcional
Muito frequente (99-80%)
90%prev.
Incapacidade de andar
Muito frequente (99-80%)
90%prev.
Comprometimento cognitivo
Muito frequente (99-80%)
90%prev.
Regressão do desenvolvimento
Muito frequente (99-80%)
90%prev.
Atraso do neurodesenvolvimento
Muito frequente (99-80%)
90%prev.
Descargas epileptiformes multifocais
Muito frequente (99-80%)
49sintomas
Muito frequente (6)
Frequente (9)
Ocasional (9)
Muito raro (1)
Sem dados (24)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 49 características clínicas mais associadas, ordenadas por frequência.

Déficit motor funcionalFunctional motor deficit
Muito frequente (99-80%)90%
Incapacidade de andarInability to walk
Muito frequente (99-80%)90%
Comprometimento cognitivoCognitive impairment
Muito frequente (99-80%)90%
Regressão do desenvolvimentoDevelopmental regression
Muito frequente (99-80%)90%
Atraso do neurodesenvolvimentoNeurodevelopmental delay
Muito frequente (99-80%)90%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2025
Total histórico124PubMed
Últimos 10 anos113publicações
Pico202218 papers
Linha do tempo
2025Hoje · 2026🧪 2017Primeiro ensaio clínico📈 2022Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

9 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive, X-linked recessive.

PLCB11-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1Disease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors (PubMed:9188725). Regulates the function of the endothelial barrier

LOCALIZAÇÃO

Nucleus membraneCytoplasm

VIAS BIOLÓGICAS (8)
Synthesis of IP3 and IP4 in the cytosolPLC beta mediated eventsG alpha (q) signalling eventsG beta:gamma signalling through PLC betaCa2+ pathway
MECANISMO DE DOENÇA

Developmental and epileptic encephalopathy 12

A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.

EXPRESSÃO TECIDUAL(Ubíquo)
Brain Frontal Cortex BA9
16.7 TPM
Brain Caudate basal ganglia
10.1 TPM
Cólon sigmoide
8.6 TPM
Brain Putamen basal ganglia
8.1 TPM
Córtex cerebral
8.0 TPM
OUTRAS DOENÇAS (2)
developmental and epileptic encephalopathy, 12malignant migrating partial seizures of infancy
HGNC:15917UniProt:Q9NQ66
PIGAPhosphatidylinositol N-acetylglucosaminyltransferase subunit ADisease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis

LOCALIZAÇÃO

Rough endoplasmic reticulum membrane

VIAS BIOLÓGICAS (1)
Synthesis of glycosylphosphatidylinositol (GPI)
MECANISMO DE DOENÇA

Paroxysmal nocturnal hemoglobinuria 1

A disorder characterized by hemolytic anemia with hemoglobinuria, thromboses in large vessels, and a deficiency in hematopoiesis. Red blood cell breakdown with release of hemoglobin into the urine is manifested most prominently by dark-colored urine in the morning.

EXPRESSÃO TECIDUAL(Ubíquo)
Pulmão
15.2 TPM
Skin Not Sun Exposed Suprapubic
11.5 TPM
Linfócitos
10.6 TPM
Tireoide
9.4 TPM
Skin Sun Exposed Lower leg
8.8 TPM
OUTRAS DOENÇAS (5)
ferro-cerebro-cutaneous syndromeparoxysmal nocturnal hemoglobinuria 1multiple congenital anomalies-hypotonia-seizures syndrome 2paroxysmal nocturnal hemoglobinuria
HGNC:8957UniProt:P37287
TBC1D24TBC1 domain family member 24Disease-causing germline mutation(s) (loss of function) inTolerante
FUNÇÃO

May act as a GTPase-activating protein for Rab family protein(s) (PubMed:20727515, PubMed:20797691). Involved in neuronal projections development, probably through a negative modulation of ARF6 function (PubMed:20727515). Involved in the regulation of synaptic vesicle trafficking (PubMed:31257402)

LOCALIZAÇÃO

Cell membraneCytoplasmCytoplasmic vesicle membranePresynapse

VIAS BIOLÓGICAS (1)
TBC/RABGAPs
MECANISMO DE DOENÇA

Familial infantile myoclonic epilepsy

A subtype of idiopathic epilepsy starting in early infancy and manifesting as myoclonic seizures, febrile convulsions, and tonic-clonic seizures.

VIAS REACTOME (1)
EXPRESSÃO TECIDUAL(Ubíquo)
Cerebelo
27.8 TPM
Cérebro - Hemisfério cerebelar
26.6 TPM
Brain Frontal Cortex BA9
11.4 TPM
Córtex cerebral
11.2 TPM
Pituitária
9.4 TPM
INTERAÇÕES PROTEICAS (2)
OUTRAS DOENÇAS (11)
familial infantile myoclonic epilepsyrolandic epilepsy-paroxysmal exercise-induced dystonia-writer's cramp syndromeautosomal dominant nonsyndromic hearing loss 65autosomal recessive nonsyndromic hearing loss 86
HGNC:29203UniProt:Q9ULP9
SLC12A5Solute carrier family 12 member 5Disease-causing germline mutation(s) (loss of function) inAltamente restrito
FUNÇÃO

Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (PubMed:12106695). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262)

LOCALIZAÇÃO

Cell membraneCell projection, dendrite

VIAS BIOLÓGICAS (1)
Cation-coupled Chloride cotransporters
MECANISMO DE DOENÇA

Developmental and epileptic encephalopathy 34

A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE34 is characterized by onset of refractory migrating focal seizures in infancy. Affected children show developmental regression and are severely impaired globally.

EXPRESSÃO TECIDUAL(Tecido-específico)
Cérebro - Hemisfério cerebelar
208.8 TPM
Cerebelo
204.3 TPM
Brain Frontal Cortex BA9
97.0 TPM
Córtex cerebral
73.3 TPM
Brain Nucleus accumbens basal ganglia
51.3 TPM
OUTRAS DOENÇAS (3)
developmental and epileptic encephalopathy, 34malignant migrating partial seizures of infancyepilepsy, idiopathic generalized, susceptibility to, 14
HGNC:13818UniProt:Q9H2X9
SLC25A22Mitochondrial glutamate carrier 1Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Mitochondrial glutamate/H(+) symporter. Responsible for the transport of glutamate from the cytosol into the mitochondrial matrix with the concomitant import of a proton (PubMed:11897791). Plays a role in the control of glucose-stimulated insulin secretion (By similarity)

LOCALIZAÇÃO

Mitochondrion inner membrane

VIAS BIOLÓGICAS (2)
SLC-mediated transport of neurotransmittersMalate-aspartate shuttle
MECANISMO DE DOENÇA

Developmental and epileptic encephalopathy 3

A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. DEE3 is characterized by a very early onset, erratic and fragmentary myoclonus, massive myoclonus, partial motor seizures and late tonic spasms. The prognosis is poor, with no effective treatment, and children with the condition either die within 1 to 2 years after birth or survive in a persistent vegetative state.

EXPRESSÃO TECIDUAL(Ubíquo)
Cerebelo
172.4 TPM
Cérebro - Hemisfério cerebelar
161.2 TPM
Brain Frontal Cortex BA9
119.4 TPM
Córtex cerebral
112.9 TPM
Brain Anterior cingulate cortex BA24
111.3 TPM
OUTRAS DOENÇAS (3)
developmental and epileptic encephalopathy, 3malignant migrating partial seizures of infancyearly-infantile DEE
HGNC:19954UniProt:Q9H936
KCNQ2Potassium voltage-gated channel subfamily KQT member 2Disease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:24277843, PubMed:28793216, PubMed:9836639). M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers (PubMed:10781098, PubMed:14534157, PubMed:32884139, PubMed:37857637, PubMed:9836639). The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determ

LOCALIZAÇÃO

Cell membrane

VIAS BIOLÓGICAS (2)
Interaction between L1 and AnkyrinsVoltage gated Potassium channels
MECANISMO DE DOENÇA

Seizures, benign familial neonatal 1

A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia.

EXPRESSÃO TECIDUAL(Tecido-específico)
Cerebelo
166.0 TPM
Cérebro - Hemisfério cerebelar
146.5 TPM
Córtex cerebral
68.1 TPM
Brain Frontal Cortex BA9
64.1 TPM
Brain Anterior cingulate cortex BA24
50.1 TPM
OUTRAS DOENÇAS (7)
seizures, benign familial neonatal, 1developmental and epileptic encephalopathy, 7seizures, benign familial infantile, 3malignant migrating partial seizures of infancy
HGNC:6296UniProt:O43526
KCNT1Potassium channel subfamily T member 1Disease-causing germline mutation(s) (gain of function) inTolerante
FUNÇÃO

Sodium-activated K(+) channel (PubMed:37494189). Acts as an important mediator of neuronal membrane excitability (PubMed:37494189). Contributes to the delayed outward currents (By similarity). Regulates neuronal bursting in sensory neurons (By similarity). Contributes to synaptic development and plasticity (By similarity)

LOCALIZAÇÃO

Cell membrane

MECANISMO DE DOENÇA

Developmental and epileptic encephalopathy 14

A rare epileptic encephalopathy of infancy that combines pharmacoresistant seizures with developmental delay. This severe neurologic disorder is characterized by onset in the first 6 months of life of refractory focal seizures and arrest of psychomotor development. Ictal EEG shows discharges that arise randomly from various areas of both hemispheres and migrate from one brain region to another.

EXPRESSÃO TECIDUAL(Tecido-específico)
Cerebelo
94.7 TPM
Cérebro - Hemisfério cerebelar
80.1 TPM
Córtex cerebral
44.1 TPM
Brain Frontal Cortex BA9
30.4 TPM
Baço
20.2 TPM
OUTRAS DOENÇAS (4)
developmental and epileptic encephalopathy, 14autosomal dominant nocturnal frontal lobe epilepsy 5malignant migrating partial seizures of infancyautosomal dominant nocturnal frontal lobe epilepsy
HGNC:18865UniProt:Q5JUK3
SCN2ASodium channel protein type 2 subunit alphaDisease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1325650, PubMed:17021166, PubMed:28256214, PubMed:29844171). Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory (By simi

LOCALIZAÇÃO

Cell membrane

VIAS BIOLÓGICAS (3)
Interaction between L1 and AnkyrinsPhase 0 - rapid depolarisationSensory perception of sweet, bitter, and umami (glutamate) taste
MECANISMO DE DOENÇA

Seizures, benign familial infantile, 3

A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant.

EXPRESSÃO TECIDUAL(Tecido-específico)
Cérebro - Hemisfério cerebelar
70.3 TPM
Cerebelo
65.2 TPM
Brain Frontal Cortex BA9
19.3 TPM
Córtex cerebral
11.5 TPM
Brain Nucleus accumbens basal ganglia
9.1 TPM
OUTRAS DOENÇAS (10)
seizures, benign familial infantile, 3episodic ataxia, type 9developmental and epileptic encephalopathy, 11complex neurodevelopmental disorder
HGNC:10588UniProt:Q99250
SCN1ASodium channel protein type 1 subunit alphaDisease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient.

LOCALIZAÇÃO

Cell membrane

VIAS BIOLÓGICAS (2)
Interaction between L1 and AnkyrinsPhase 0 - rapid depolarisation
MECANISMO DE DOENÇA

Generalized epilepsy with febrile seizures plus 2

A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.

EXPRESSÃO TECIDUAL(Tecido-específico)
Brain Frontal Cortex BA9
15.1 TPM
Cérebro - Hemisfério cerebelar
10.7 TPM
Cerebelo
9.3 TPM
Córtex cerebral
8.9 TPM
Hipotálamo
6.3 TPM
OUTRAS DOENÇAS (13)
developmental and epileptic encephalopathy, 6Ageneralized epilepsy with febrile seizures plus, type 2developmental and epileptic encephalopathy 6Bfamilial hemiplegic migraine
HGNC:10585UniProt:P35498

Variantes genéticas (ClinVar)

683 variantes patogênicas registradas no ClinVar.

🧬 PLCB1: NM_015192.4(PLCB1):c.3464A>G (p.Lys1155Arg) ()
🧬 PLCB1: NM_015192.4(PLCB1):c.3357del (p.Lys1119fs) ()
🧬 PLCB1: NM_015192.4(PLCB1):c.991C>T (p.His331Tyr) ()
🧬 PLCB1: NM_015192.4(PLCB1):c.3423+11802G>T ()
🧬 PLCB1: NM_015192.4(PLCB1):c.521T>C (p.Ile174Thr) ()
Ver todas no ClinVar

Classificação de variantes (ClinVar)

Distribuição de 6 variantes classificadas pelo ClinVar.

6
Patogênica (100.0%)
VARIANTES MAIS SIGNIFICATIVAS
SCN2A: NM_001040142.2(SCN2A):c.2896G>C (p.Val966Leu) [Likely pathogenic]
LOC126806396: GRCh38/hg38 2q24.3(chr2:165155128-166062451)x1 [Pathogenic]
SCN2A: NM_001040142.2(SCN2A):c.4018G>A (p.Val1340Ile) [Pathogenic]
SCN2A: NM_001040142.2(SCN2A):c.4901G>T (p.Gly1634Val) [Pathogenic]
SCN2A: NM_001040142.2(SCN2A):c.4886G>A (p.Arg1629His) [Pathogenic/Likely pathogenic]

Diagnóstico

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Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Carregando informações de tratamento...

Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Convulsões focais migratórias malignas da infância

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Publicações mais relevantes

Timeline de publicações
117 papers (10 anos)
#1

Identification of New KCNT1-Epilepsy Drugs by In Silico, Cell, and Drosophila Modeling.

Annals of neurology2025 Dec

Hyperactive KCNT1 potassium channels, caused by gain-of-function mutations, are associated with a range of epilepsy disorders. Patients typically experience drug-resistant seizures and, in cases with infantile onset, developmental regression can follow. KCNT1-related disorders include epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. There are currently no effective treatments for KCNT1 epilepsies, but suppressing overactive channels poses a potential strategy. Using the KCNT1 channel structure we in silico screened a library of known drugs for those predicted to block the channel pore to inhibit channel activity. Cellular KCNT1 channel inhibition was analyzed using electrophysiology and Drosophila bang-sensitive assays were used to analyze seizure suppression. Brain penetration of one drug was analyzed using liquid chromatography-mass spectrometry in a mouse. Eight known drugs were investigated in vitro for their effects on patient-specific mutant KCNT1 channels, with 4 drugs showing significant reduction of K+ current amplitudes. The action of the 4 drugs was then analyzed in vivo and 2 were found to reduce the seizure phenotype in humanized Drosophila KCNT1 epilepsy models. One drug, antrafenine, was shown to cross the blood-brain barrier in mice. This study identified a known drug, antrafenine, that reduces KCNT1 channel activity, reduces seizure activity in Drosophila, and crosses the blood-brain barrier in the mouse, suggesting its potential applicability as a new treatment for KCNT1 epilepsy. The sequential in silico, in vitro, and in vivo mechanism-based drug selection strategy used here may have broader application for other human disorders where a disease mechanism has been identified. ANN NEUROL 2025;98:1261-1274.

#2

Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study.

Annals of neurology2025 Jul

Gain-of-function (GoF) variants in KCNT1 encoding for potassium channels are associated with different epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), other early infantile developmental and epileptic encephalopathies, and focal epilepsy. Fluoxetine blocks currents from both wild-type (WT) and mutant KCNT1 channels with GoF in vitro features. In this study, we tested the hypothesis that treatment with fluoxetine might improve clinical outcome in patients with EIMFS carrying GoF variants in KCNT1 channels showing in vitro sensitivity to fluoxetine blockade. We enrolled three pediatric patients carring de novo KCNT1 genetic variants linked to EIMFS. Functional and pharmacological studies to assess fluoxetine's ability to counteract in vitro variant-induced functional effects were performed with patch-clamp electrophysiology on heterologous channel expression in mammalian Chinese hamster ovary cells. Neuropsychological assessment, electroencephalogram and seizure diary were evaluated at baseline and every 3 months during the study. Electrocardiography and blood levels of medications were monitored for safety. All 3 KCNT1 variants displayed GoF effects in vitro. Exposure to fluoxetine (10μM) blocked both WT and mutant KCNT1 channels, therefore, counteracting variant-induced functional effects. Treatment with fluoxetine caused a variable reduction of seizure frequency (25-75%). Improvement in visual attention, participation, and muscle tone was also reported. No adverse events were reported except for transient dyskinesia in 1 patient, which was probably related to an increase in fluoxetine plasma level. Fluoxetine may be a potential targeted medication in EIMFS caused by KCNT1 GoF variants. Further research is needed to assess its long-term efficacy and safety. ANN NEUROL 2025;98:48-61.

#3

Novel Gain of Function Mouse Model of KCNT1-Related Epilepsy.

bioRxiv : the preprint server for biology2025 Oct 25

KCNT1 -related epilepsy is an autosomal dominant neurodevelopmental disorder with at least 64 known human variants, each with unique electrophysiological and epileptic characteristics. A multi-disciplinary collaboration generated a novel mouse model (C57BL/6- Kcnt1 em1Bryd ) carrying the G269S variant, corresponding to human G288S, located within the coding region of the channel pore. Network excitability of cultured cortical neurons from Kcnt1 +/G269S exhibited sustained hyperexcitability and hypersynchronous bursting while Kcnt1 G269S/G269S neurons showed early excessive bursting followed by network collapse, suggesting excitotoxicity. Kcnt1 +/G269S displayed poor motor coordination, erratic breathing, and increased apneas. Critically, Kcnt1 +/G269S were more susceptible to thermal-induced seizures in early life. In summary, these data: (i) provide a novel mouse model of KCNT1-related epilepsy, (ii) provide strong in vitro evidence of neuronal hyperexcitability, (iii) illustrate early-life seizures as a functional outcome measure, and (iv) lay the groundwork for future analysis of neural activity in vivo and modeling circuit level dynamics in vitro and in silico . Gain-of-function mutations in the sodium-gated potassium channel KCNT1 have been linked to pediatric epilepsy of varying severity. The human KCNT1 variant G288S (G269S in mice) is linked to Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE), Epilepsy of Infancy with Migrating Focal Seizures (EIMFS), and other severe developmental epileptic encephalopathies. There are currently no therapeutics to prevent the progression of KCNT1 -related epilepsy, therefore, the scientific community requires a novel mouse model that is well characterized, in vitro and in vivo, to screen and assess targeted therapeutics. Herein, we engineered a novel mouse to assess developmental and adult phenotypes resulting from the G288S/G269S variant, in vitro and in vivo , to advance translation toward therapeutic testing for individuals with KCNT1 -related epilepsy.

#4

Association between phenotypes and genotype of developmental and epileptic encephalopathy in next-generation sequencing methods in infants: A scoping review.

The Medical journal of Malaysia2025 Jul

Developmental and epileptic encephalopathy (DEE) is epilepsy related to developmental impairment that may be caused by both the underlying etiology (developmental encephalopathy) and superimposed epileptic activity (epileptic encephalopathy). The origin of DEE and the causes of its variations remain unknown. Owing the lack of clarity regarding the role of genetic variables in DEE, we conducted a scoping review to qualitatively identify the genes most important in the development of DEE to provide an up-to-date review. We searched all published studies related to the genetic factors of DEE. The identified publications were screened and selected by the authors on basis of on inclusion and exclusion criteria and assessed for methodological quality. Eighteen articles were included. The extracted data included age of onset, sex, gene mutations and inheritance (e.g. nucleotide change, protein change, and family testing), clinical manifestation, electroencephalogram, imaging, medication, and outcomes. A total of 18 studies were included in this scoping review. The most frequently reported gene variants were STXBP1 in Ohtahara Syndrome, SLC1A2 in Early Myoclonic Encephalopathy (EME), CDKL5 in West Syndrome, SCN1A in Dravet Syndrome, and KCNT1 in Epilepsy of Infancy with Migrating Focal Seizures (EIMFS). Each gene was associated with distinct electroclinical features, including differences in age of onset, seizure type, EEG patterns, and developmental outcomes. While genotype and phenotype associations were heterogeneous, certain variants showed consistent patterns indicative of more severe disease courses. This review identified key gene variants commonly associated with early-onset DEE in infants, particularly STXBP1, SLC1A2, CDKL5, SCN1A, and KCNT1, each linked to unique clinical presentations and outcomes. These findings support the clinical utility of next-generation sequencing (NGS) for early diagnosis and tailored treatment planning in DEE. Understanding genotype-phenotype correlations may enhance prognostication and highlight potential avenues for targeted therapy in future research.

#5

Genetic etiologies with a large NGS panel in a monocentric cohort of 1000 patients with pediatric onset epilepsies.

Epilepsia open2025 Aug

Genetic testing is now included in the diagnostic assessment of childhood onset epilepsies. We evaluated the yield of a targeted next generation sequencing (TNGS) panel dedicated to pediatric epilepsies. We tested by TNGS panel 1000 consecutive patients presenting with childhood onset epilepsies and including mainly patients with early onset epilepsies (under 2 years, 61%). Causal variants were identified in 31% of patients, spanning 78 different genes. Patients with benign familial neonatal/infantile epilepsy (BFN/IS) exhibited the highest rate of positive findings (82%). Developmental and epileptic encephalopathies (DEEs) had a global diagnostic yield of 37%, with epilepsy of infancy with migrating focal seizures (EIMFSI) and Dravet syndrome (DS) presenting the highest yield in this group (78%) and early infantile DEE (EIDEE) laying next with a yield of 43%. The lowest rates of genetic diagnosis were observed in infantile epileptic spasms syndrome (IESS, 17%), epilepsy with myoclonic-atonic seizures (EMAtS, 19%), and DEE-SWAS (14%). Patients with GEFS+ had a yield of 16%. Among patients with developmental encephalopathies and refractory seizures with onset after 2 years, TNGS yielded a 33% diagnostic rate. Atypical absences yielded 16%, focal epilepsy yielded 18%, and generalized epilepsies with refractory seizures yielded 13%. These groups exhibited a high genetic heterogeneity. TNGS is an effective first-step genetic screening in patients with high diagnostic yields (BFN/IS, EIMFS, DS, EIDEE) and for epilepsy syndromes associated with one or a few major genes (BFN/IS, EIMFS, DS, GEFS+, DEE-SWAS). Whole exome or genome sequencing (WES/WGS) should be considered as a second step in these groups with a probably relevant Mendelian inheritance. WES/WGS could be proposed as first-tier analysis in patients with IESS, EMAtS, generalized or focal epilepsies refractory to ASMs, and developmental encephalopathies with seizure onset after 2 years. However, the lower diagnostic yield obtained in these groups may suggest a complex inheritance. This study emphasizes the importance of accurately identifying different types of epilepsy and epilepsy syndromes to improve genetic testing strategies. We suggest that a targeted gene panel can be a good first step for some genetic conditions, such as benign familial neonatal/infantile epilepsy, Dravet syndrome, and epilepsy of infancy with migrating focal seizures.

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Epilepsia open
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[Clinical features and gene mutations in epilepsy of infancy with migrating focal seizures].

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Epileptic disorders : international epilepsy journal with videotape
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Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. Identification of New KCNT1-Epilepsy Drugs by In Silico, Cell, and Drosophila Modeling.
    Annals of neurology· 2025· PMID 40944494mais citado
  2. Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study.
    Annals of neurology· 2025· PMID 39981956mais citado
  3. Novel Gain of Function Mouse Model of KCNT1-Related Epilepsy.
    bioRxiv : the preprint server for biology· 2025· PMID 40777472mais citado
  4. Association between phenotypes and genotype of developmental and epileptic encephalopathy in next-generation sequencing methods in infants: A scoping review.
    The Medical journal of Malaysia· 2025· PMID 40740097mais citado
  5. Genetic etiologies with a large NGS panel in a monocentric cohort of 1000 patients with pediatric onset epilepsies.
    Epilepsia open· 2025· PMID 40347095mais citado
  6. Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.
    Nat Med· 2026· PMID 41981306recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:293181(Orphanet)
  2. MONDO:0017385(MONDO)
  3. Epilepsia(PCDT · Ministério da Saúde)
  4. GARD:12919(GARD (NIH))
  5. Variantes catalogadas(ClinVar)
  6. Busca completa no PubMed(PubMed)
  7. Q3589156(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Convulsões focais migratórias malignas da infância
Compêndio · Raras BR

Convulsões focais migratórias malignas da infância

ORPHA:293181 · MONDO:0017385
🇧🇷 Brasil SUS
Geral
Prevalência
<1 / 1 000 000
Casos
114 casos conhecidos
Herança
Autosomal dominant, Autosomal recessive, X-linked recessive
CID-10
G40.0 · Epilepsia e síndromes epilépticas idiopáticas definidas por sua localização (focal) (parcial) com crises de início focal
CID-11
Início
Infancy, Neonatal
Prevalência
0.0 (Worldwide)
MedGen
UMLS
C3494976
Repurposing
31 candidatos
aminohydroxybutyric-acidcarbonic anhydrase inhibitor
diclofenamidesuccinimide antiepileptic
ethosuximideglutamate receptor antagonist
+17 outros
EuropePMC
Wikidata
Papers 10a
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