Infantile spasms: genes and variants

Genes linked to Infantile spasms

• 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.

  3 disease-causing and 0 uncertain variants in SCN2A are linked to Infantile spasms.

• CDKL5: Cyclin-dependent kinase-like 5

  It phosphorylates neuronal substrates involved in synapse development, cytoskeletal organization, and signaling during early brain maturation. Loss-of-function variants cause CDKL5 deficiency disorder with very early epilepsy and severe developmental impairment.

  0 disease-causing and 1 uncertain variants in CDKL5 are linked to Infantile spasms.

• GRIN2B: Glutamate receptor ionotropic, NMDA 2B

  It confers distinct developmental and signaling properties on NMDA receptors and is highly expressed during early brain development. De novo pathogenic variants can cause intellectual disability, developmental delay, epilepsy, abnormal movements, and autism-related phenotypes.

  0 disease-causing and 0 uncertain variants in GRIN2B are linked to Infantile spasms.

• SCN8A: Sodium channel protein type 8 subunit alpha

  The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies.

  1 disease-causing and 0 uncertain variants in SCN8A are linked to Infantile spasms.

Weakly linked (only a few uncertain records): KCNT1 and STXBP1.

Known disease-causing variants in Infantile spasms

Same protein, different disease

• Seizures, benign familial infantile, 3 is also caused by SCN2A variants; they fall mostly in different places as the Infantile spasms variants (167 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN2A variants; they fall mostly in different places as the Infantile spasms variants (22 disease-causing).
• Episodic ataxia type 2 is also caused by SCN2A variants; they fall mostly in different places as the Infantile spasms variants (15 disease-causing).
• West syndrome is also caused by SCN2A variants; they fall mostly in different places as the Infantile spasms variants (11 disease-causing).
• Benign familial infantile epilepsy is also caused by SCN2A variants; they fall mostly in different places as the Infantile spasms variants (6 disease-causing).
• Early-infantile DEE is also caused by SCN8A variants; they fall mostly in different places as the Infantile spasms variants (90 disease-causing).
• Cognitive impairment with or without cerebellar ataxia is also caused by SCN8A variants; they fall mostly in different places as the Infantile spasms variants (22 disease-causing).
• Seizures, benign familial infantile, 3 is also caused by SCN8A variants; they fall mostly in different places as the Infantile spasms variants (12 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN8A variants; they fall mostly in different places as the Infantile spasms variants (8 disease-causing).
• Autosomal recessive inheritance is also caused by SCN8A variants; they fall mostly in different places as the Infantile spasms variants (3 disease-causing).

Diseases related to Infantile spasms

• Complex neurodevelopmental disorder, also linked to GRIN2B, SCN2A and SCN8A
• Epilepsy, also linked to GRIN2B, SCN2A and SCN8A
• Seizures, benign familial infantile, 3, also linked to SCN2A and SCN8A
• Amyotrophic lateral sclerosis, also linked to SCN2A and SCN8A
• Cardiac arrhythmia, also linked to SCN2A and SCN8A
• Genetic developmental and epileptic encephalopathy, also linked to SCN2A and SCN8A
• Lennox-Gastaut syndrome, also linked to SCN2A and SCN8A
• Early-infantile DEE, also linked to SCN8A
• Episodic ataxia type 2, also linked to SCN2A
• Alzheimer disease, also linked to GRIN2B
• Rett syndrome, also linked to CDKL5
• Angelman syndrome-like, also linked to CDKL5

Frequently asked questions

Which genes are linked to Infantile spasms?

In CATVariant, Infantile spasms is linked to 4 analyzed proteins: SCN2A (Sodium channel protein type 2 subunit alpha), CDKL5 (Cyclin-dependent kinase-like 5), GRIN2B (Glutamate receptor ionotropic, NMDA 2B) and SCN8A (Sodium channel protein type 8 subunit alpha).

How many genetic variants are linked to Infantile spasms?

7 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1 are of uncertain significance or have conflicting reports.

Which uncertain variants in Infantile spasms 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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