Self-limited epilepsy with centrotemporal spikes: genes and variants

Genes linked to Self-limited epilepsy with centrotemporal spikes

• RELN: Reelin

  It is secreted during brain development to guide neuronal migration and cortical layering and later modulates synaptic plasticity. Biallelic loss-of-function variants cause lissencephaly with cerebellar hypoplasia, while heterozygous variants can be associated with epilepsy.

  1 disease-causing and 0 uncertain variants in RELN are linked to Self-limited epilepsy with centrotemporal spikes.

• GRIN2A: Glutamate receptor ionotropic, NMDA 2A

  It helps determine the kinetics and signaling properties of NMDA receptors, particularly in cortical circuits involved in language and epilepsy. Pathogenic variants cause a spectrum of developmental epileptic encephalopathies and epilepsy-aphasia disorders.

  1 disease-causing and 0 uncertain variants in GRIN2A are linked to Self-limited epilepsy with centrotemporal spikes.

• GABRG2: Gamma-aminobutyric acid receptor subunit gamma-2

  The gene product supplies the gamma-2 subunit of synaptic GABA-A receptors, which are pentameric chloride channels activated by the inhibitory neurotransmitter GABA. The subunit helps receptor assembly and localization at neuronal membranes, and GABRG2 variants are associated with several epilepsy syndromes.

  0 disease-causing and 0 uncertain variants in GABRG2 are linked to Self-limited epilepsy with centrotemporal spikes.

• CHD2: ATP-dependent chromatin remodeler CHD2

  It remodels chromatin to regulate transcription and is particularly important for neuronal development and activity-dependent gene expression. Haploinsufficiency commonly causes developmental and epileptic encephalopathy, often with photosensitive seizures and intellectual disability.

  2 disease-causing and 0 uncertain variants in CHD2 are linked to Self-limited epilepsy with centrotemporal spikes.

• KCNQ3: Potassium voltage-gated channel subfamily KQT member 3

  Together with KCNQ2, its slowly activating current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants can cause self-limited neonatal epilepsy or more severe developmental and epileptic encephalopathy.

  1 disease-causing and 0 uncertain variants in KCNQ3 are linked to Self-limited epilepsy with centrotemporal spikes.

• GRIN1: Glutamate receptor ionotropic, NMDA 1

  It provides an obligatory subunit of NMDA receptors and is essential for glutamate-dependent synaptic transmission, calcium signaling, and plasticity. Pathogenic variants can cause GRIN1-related neurodevelopmental disorder with intellectual disability, movement abnormalities, epilepsy, and cortical visual impairment.

  1 disease-causing and 0 uncertain variants in GRIN1 are linked to Self-limited epilepsy with centrotemporal spikes.

• SCN2A: Sodium channel protein type 2 subunit alpha

  The protein forms Nav1.2, a voltage-gated sodium channel that carries sodium current during neuronal action potentials. By shaping neuronal excitability and signal propagation, it supports brain circuits involved in development, learning, and seizure susceptibility.

  1 disease-causing and 0 uncertain variants in SCN2A are linked to Self-limited epilepsy with centrotemporal spikes.

• SLC2A1: Solute carrier family 2, facilitated glucose transporter member 1

  It provides basal glucose uptake in many tissues and is the principal route for glucose entry across the blood-brain barrier. Haploinsufficiency causes GLUT1 deficiency syndrome with epilepsy, developmental impairment, and movement disorders from inadequate brain glucose delivery.

  1 disease-causing and 0 uncertain variants in SLC2A1 are linked to Self-limited epilepsy with centrotemporal spikes.

• CNTNAP2: Contactin-associated protein-like 2

  It organizes specialized neuronal membrane domains and contributes to axonal development, synaptic connectivity, and clustering of potassium channels at juxtaparanodes. Biallelic loss-of-function variants can cause severe neurodevelopmental disease with epilepsy and language impairment, while heterozygous associations are more complex.

  0 disease-causing and 0 uncertain variants in CNTNAP2 are linked to Self-limited epilepsy with centrotemporal spikes.

Weakly linked (only a few uncertain records): DEPDC5, WWOX, KCNT1, PCDH19 and SLC6A1.

Known disease-causing variants in Self-limited epilepsy with centrotemporal spikes

Which prediction tools work for Self-limited epilepsy with centrotemporal spikes

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• PolyPhen-2: 60 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Familial temporal lobe epilepsy 7 is also caused by RELN variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (4 disease-causing).
• Landau-Kleffner syndrome is also caused by GRIN2A variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (85 disease-causing).
• Benign neonatal seizures is also caused by KCNQ3 variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (13 disease-causing).
• Seizures, benign familial neonatal, 1 is also caused by KCNQ3 variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (7 disease-causing).
• Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant is also caused by GRIN1 variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (55 disease-causing).
• Seizures, benign familial infantile, 3 is also caused by SCN2A variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (167 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN2A variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (22 disease-causing).
• Episodic ataxia type 2 is also caused by SCN2A variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (15 disease-causing).
• West syndrome is also caused by SCN2A variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (11 disease-causing).
• Benign familial infantile epilepsy is also caused by SCN2A variants; they fall mostly in different places as the Self-limited epilepsy with centrotemporal spikes variants (6 disease-causing).

Diseases related to Self-limited epilepsy with centrotemporal spikes

• Epilepsy, also linked to GABRG2, GRIN2A, KCNQ3 and SCN2A
• Seizures, benign familial infantile, 3, also linked to KCNQ3 and SCN2A
• Complex neurodevelopmental disorder, also linked to CHD2 and SCN2A
• Genetic developmental and epileptic encephalopathy, also linked to GABRG2 and SCN2A
• Lennox-Gastaut syndrome, also linked to GABRG2 and SCN2A
• Amyotrophic lateral sclerosis, also linked to SCN2A
• Episodic ataxia type 2, also linked to SCN2A
• Alzheimer disease, also linked to GRIN2A
• Generalized epilepsy with febrile seizures plus, also linked to GABRG2
• Cardiac arrhythmia, also linked to SCN2A
• Landau-Kleffner syndrome, also linked to GRIN2A
• EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2, also linked to GABRG2

Frequently asked questions

Which genes are linked to Self-limited epilepsy with centrotemporal spikes?

In CATVariant, Self-limited epilepsy with centrotemporal spikes is linked to 9 analyzed proteins: RELN (Reelin), GRIN2A (Glutamate receptor ionotropic, NMDA 2A), GABRG2 (Gamma-aminobutyric acid receptor subunit gamma-2), CHD2 (ATP-dependent chromatin remodeler CHD2), KCNQ3 (Potassium voltage-gated channel subfamily KQT member 3), GRIN1 (Glutamate receptor ionotropic, NMDA 1) and 3 more.

How many genetic variants are linked to Self-limited epilepsy with centrotemporal spikes?

33 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.

Which uncertain variants in Self-limited epilepsy with centrotemporal spikes look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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