Table 2.

Biologic classification of infantile spasms. Genes are organized into groups by Gene Ontology molecular function and roles in or effect on central nervous system development.

Group	Neurodevelopmental phenotype besides ISS	Gene(s)	GO Molecular Function	Role in/Effect on CNS development	References
A	Autistic features Movement disorder Severe cognitive impairment	ARX FOXG1 MEF2C	Transcription factors	Dorsal-ventral differentiation (FOXG1) Ventral NPC proliferation GABAergic iN differentiation (ARX) GABAergic iN migration (ARX) Synapse function (secondary effect)	[181–184]
B1	Severe brain malformation Severe cognitive impairment Intractable epilepsy	DCX PAFAH1B1/LIS1 TUBA1A	Binding	Dorsal NPC proliferation GABAergic iN migration IPC proliferation Glutaminergic N migration Axonogenesis Synaptogenesis (secondary effect)	[61, 185–189]
B2	Brain malformations of TSC Severe cognitive impairment Autism Intractable epilepsy	TSC1 TSC2	Signal transduction	Dorsal NPC proliferation IPC proliferation Glutaminergic N migration Axonogenesis Synaptogenesis	[190, 191]
C1	Metabolic disease Variable cognitive impairment Variable subsequent epilepsy	GLDC PAH	Binding, catalytic activity	Neuronal and non-neuronal cell metabolism Synapse function (secondary effect)	[192, 193]
C2	Metabolic disease Intractable epilepsy	ATP7A KCNJ11	Transporter, catalytic activity	Synaptogenesis	[194–196]
D	Intractable epilepsy Severe cognitive impairment	GRIN1 GRIN2A MAGI2 SPTAN1 STXBP1	Binding	Synaptogenesis	[19, 22, 24, 55, 197, 198]
E	Intractable epilepsy Retinitis	SLC25A22	Transporter	Synapse function (secondary effect)	[23]

Abbreviations: iN = interneurons; IPC = intermediate progenitor cells; N = neurons; NPC = neuronal progenitor cells