Epilepsy Mechanisms in Down Syndrome: Genetic and Pathophysiological Perspectives Across the Lifespan

Topic: Brain proteins, microglia and lab models

Down syndrome (trisomy 21) is the most common genetic cause of intellectual disability. Seizures are a frequent comorbidity in individuals with Down syndrome and can exert significant negative consequences on cognitive capacity and quality of life. In Down syndrome, seizures cluster at two extremes of the lifespan. In the first year of life, infantile epileptic spasms syndrome affects 5–10% of children with Down syndrome. The second peak occurs after age 30 years, when myoclonic seizures appear at the time of onset of Down syndrome-related dementia of the Alzheimer type (late-onset myoclonic epilepsy in Down syndrome or LOMEDS). While epilepsy at these two disparate time points has been long recognized in the Down syndrome population, the mechanisms underlying seizure pathogenesis have not been studied in detail. For example, it is not known whether the brain developmental abnormalities that characterize Down syndrome are primarily responsible for the epilepsies or whether distinct mechanisms underlie seizures at the two ages. This narrative review addresses possible mechanisms of seizure propensity across the lifespan, with special reference to potential age-specific treatments.

Key findings

• Seizures are a frequent comorbidity in individuals with Down syndrome and can exert significant negative consequences on cognitive capacity and quality of life.

Why it matters

This review discusses that seizures are common in Down syndrome, with peaks in infancy and after age 30 when dementia often begins, but the mechanisms are not well understood. It calls for more research into age-specific treatments for seizures in this population.

Study details

• Study designnarrative review
• Evidence strengthLow

Read the original

• DOI: 10.3390/jcm15197471
• PubMed: 42881935
• Original source →
• Free full text: Journal of Clinical Medicine →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{stafstrom2026-0b7e245a,
  author  = {Stafstrom, Carl E. and Shao, Li‐Rong},
  title   = {{Epilepsy Mechanisms in Down Syndrome: Genetic and Pathophysiological Perspectives Across the Lifespan}},
  journal = {Journal of Clinical Medicine},
  year    = {2026},
  doi     = {10.3390/jcm15197471},
  pmid    = {42881935},
  url     = {https://doi.org/10.3390/jcm15197471}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Down syndrome Nature reviews. Disease primers · 2020-02-06 · usefulness score 56/100 · How common it is

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• Down syndrome: age-dependence of PiB binding in postmortem frontal cortex across the lifespan Neurobiology of aging · 2017-03-14 · usefulness score 43/100
• Down syndrome: Cognitive and behavioral functioning across the lifespan American journal of medical genetics. Part C, Seminars in medical genetics · 2015-05-18 · usefulness score 36/100
• Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer's disease, Down syndrome, and Parkinson's disease NPJ dementia · 2025-10-27 · usefulness score 41/100
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Also tagged “down”

527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.

• Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants Proceedings of the National Academy of Sciences of the United States of America · 1992-02-01 · usefulness score 38/100 · Down syndrome and Alzheimer's
• Biomarkers of oxidative stress are significantly elevated in Down syndrome Free radical biology & medicine · 1998-12-01 · usefulness score 47/100 · Down syndrome and Alzheimer's
• Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial Trials · 2014-06-03 · usefulness score 57/100 · Treatments

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• The brain in Down syndrome 2001 · Down syndrome and Alzheimer's
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