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Research paper

Epilepsy in pediatric patients with PTEN hamartoma tumor syndrome: First step in recommendations for clinical management

Cohort study of epilepsy in PHTS. Characterizes phenotypic spectrum, MRI features, seizure types, treatment response, and the overlap with macrocephaly and ASD.

Indexed context

Jonker-Schieving CM, et al.

ptenphtsepilepsycohortmacrocephaly2026

Markdown path

content/research/papers/2026-jonker-schieving-phts-epilepsy-cohort.md

Findings

Cohort study of epilepsy in PHTS. Characterizes phenotypic spectrum, MRI features, seizure types, treatment response, and the overlap with macrocephaly and ASD.

Why it may matter for Levi

Directly relevant to Levi's macrocephaly + DD/ASD + epilepsy phenotype. Complements Li 2024 PTEN pediatric cohort already in the corpus. PTEN variant remains a plausible candidate for mosaic reanalysis. Strengthens the argument for tissue-based PTEN sequencing.

Paper text

Jonker & Schieving (2026) — PHTS pediatric epilepsy cohort

Source

  • European Journal of Paediatric Neurology 61:36-41, 2026. Radboud University Medical Center (Nijmegen).

Why in corpus

Large contemporary pediatric PHTS (PTEN hamartoma tumor syndrome) cohort characterizing the epilepsy phenotype — directly relevant to Levi's differential (PTEN / PI3K-AKT-mTOR hypothesis).

Key findings

  • 149 pediatric PHTS patients retrospectively examined.
  • Epilepsy prevalence of 6% in the PHTS cohort.
  • Estimated PHTS prevalence in the Netherlands: 1:20,000.
  • ASD significantly associated with increased risk of developing epilepsy in PHTS (p=0.002).
  • Focal epilepsy with impaired awareness the most common seizure type.
  • MRI abnormalities did not correlate with epileptic foci on EEG — suggesting functional rather than structural epileptogenesis in PHTS.

Levi-relevant takeaways

  • Important finding for Levi: PHTS-associated epilepsy can be electrographically active without MRI correlate. This matches Levi's presentation (DEE-SWAS with structurally unremarkable MRI) and is a direct counter to the intuition that "normal MRI + negative WES rules out PHTS / PTEN."
  • ASD-plus-epilepsy has documented elevated PHTS association — Levi's phenotype (ASD + DEE-SWAS + overgrowth) is exactly the population in which PHTS is enriched.
  • Strengthens the case for including PTEN specifically in the mosaic-sensitive tissue-based testing panel (already prioritized) — germline sequencing alone does not rule out somatic/mosaic PTEN disruption.
  • Informs long-term surveillance if PTEN is ever identified: PHTS-associated cancer risk (thyroid, breast, endometrial, kidney) warrants lifetime surveillance beyond epilepsy management.