Table 2.

Key genetic syndromes with frequently associated epilepsy (not comprehensive):¹⁹

Syndrome	Genetics	Brief summary	EEG features
Classical Rett syndrome	MECP2 deletions or mutations (Autosomal dominant, most de novo) *Early onset seizure variant is associated with CDKL5 mutations/deletions. *Congenital variant is associated with FOXG1 mutations/deletions.	Progressive microcephaly, loss of purposeful hand skills, stereotypic hand movements, partial/complete loss of language, gait abnormalities. Majority develop epilepsy in childhood.	Frontocentral theta slowing. Loss of phase II sleep features. Focal or multifocal epileptiform activity.
Angelman syndrome	Maternal deletion (majority) or uniparental disomy of 15q11-q13, methylation defect of this region (deletion of the imprinting center), or UBE3 mutation or deletion (inheritance pattern varies by defect)	Severe DD or ID, severe speech impairment, gat ataxia and/or tremulousness of limbs, unique behavior of inappropriate happy demeanor. Microcephaly and seizures common.	Intermittent rhythmic delta. Epileptiform activity.
Tuberous sclerosis complex	Mutation or deletion of TSC1 or TSC2 (Autosomal dominant)	DD, typical skin findings, epilepsy, +/− autism. Also often involves renal, cardiac, and other organ system involvement.	Multifocal epileptiform activity +/− slowing, associated with tubers. Not specific.
Hypomelano- sis of Ito	Heterogeneous, frequently with mosaic chromosomal abnormalities/rearrangements including translocations, abnormal ploidy, trisomies, CNVs or mosaicism for sex chromosomes. Most found in cells from the skin lesions.	Hypopigmented skin lesions (whorls, streaks, patches) following the lines of Blaschko +/− extracutaneous manifestations. ID and epilepsy common. Often associated with malformations including hemimegalencephaly, pachygyria, cortical dysplasia, heterotopias, or others.	Not specific.
Menkes disease	Mutation or deletion of ATP7A (X-linked recessive)	Males with hypotonia, failure to thrive and seizures with onset at ~1-3 months. Typical sparse, coarse, twisted, lightly pigmented hair. Low copper/ceruloplasmin.	Epileptiform activity and seizures initially posterior predominant. May develop hypsarrhythmia. Late multifocal epileptiform activity and slowing
1p36 deletion syndrome	Deletion in the 1p36 region.	DD, ID, hypotonia, craniofacial abnormalities, congenital heart defects, precocious puberty, obesity. Epilepsy in ~50-60%. Spasms and apneic seizures are common.	Multifocal and/or generalized spikes and slowing. Some develop hypsarrhythmia.

DD= developmental delay; ID = intellectual disability