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Research paper

Epileptic encephalopathy with spike-and-wave activation in sleep associated with Tatton-Brown-Rahman syndrome responsive to highly purified cannabidiol

Case report (2026) of a pediatric TBRS patient (confirmed DNMT3A variant) who developed EE-SWAS (the ILAE 2022 umbrella that includes DEE-SWAS), was refractory to conventional antiseizure medications, and responded to highly purified cannabidiol. Full text was paywalled at ingest; abstract-level summary pending full-text review.

Indexed context

Datta AN, et al.

dnmt3atbrsdee-swasesescannabidiolpediatric-epilepsy

Markdown path

content/research/papers/2026-datta-tbrs-eeswas-cannabidiol.md

Findings

Case report (2026) of a pediatric TBRS patient (confirmed DNMT3A variant) who developed EE-SWAS (the ILAE 2022 umbrella that includes DEE-SWAS), was refractory to conventional antiseizure medications, and responded to highly purified cannabidiol. Full text was paywalled at ingest; abstract-level summary pending full-text review.

Why it may matter for Levi

The single most directly phenotype-matched publication: DNMT3A / TBRS can produce exactly Levi's EEG syndrome. Does not by itself reverse the negative germline workups, but (a) establishes TBRS as a known cause of Levi's specific epilepsy syndrome, (b) materially strengthens the case for methylation / episignature testing, and (c) opens cannabidiol as a specific second-line option if TBRS is ever confirmed and Levi relapses off steroids.

Paper text

Epileptic encephalopathy with spike-and-wave activation in sleep associated with Tatton-Brown-Rahman syndrome responsive to highly purified cannabidiol

Datta AN, et al. — Epileptic Disorders (2026). https://onlinelibrary.wiley.com/doi/10.1002/epd2.70229

Findings summary

Case report (published online 2026-03-19) of a pediatric patient with molecularly confirmed Tatton-Brown-Rahman syndrome (germline DNMT3A variant) who developed epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS), the same ILAE 2022 umbrella that contains Levi's DEE-SWAS diagnosis. The patient was refractory to conventional antiseizure medications and demonstrated response to highly purified cannabidiol (Epidiolex-class). The paper is the first published report of the specific TBRS + spike-wave-activation-in-sleep phenotype.

Full-text details (doses, EEG spike-wave index before and after, whether steroids were tried, other ASMs tried, duration of response, developmental outcome) were paywalled at the time of this literature pass and have not yet been read directly. This record will be updated when the full text is reviewed.

Relevance to Levi

This is the most directly phenotype-matched publication identified in the current literature pass. It documents that DNMT3A / TBRS can present as exactly Levi's EEG phenotype (DEE-SWAS), which is not captured in the 2018 Tatton-Brown cohort of 55 individuals and is not listed as a cardinal feature of TBRS in the GeneReviews. This case is by itself not enough to raise TBRS to a leading theory — a single case report in a gene where germline coding variants have already been excluded by two negative trio workups and a reanalysis does not reverse that negative work — but it does three things:

  1. It establishes that TBRS is a published cause of the exact EEG syndrome Levi has.
  2. It materially strengthens the case for methylation / episignature testing (EpiSign has a robust TBRS hypomethylation signature) as a functional readout that short-read WGS cannot provide.
  3. It opens cannabidiol as a specific second-line option if TBRS is later confirmed and Levi relapses off steroids or is steroid-intolerant.

Provenance