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Familial Sleep-Related Hypermotor Epilepsy

Familial Sleep-Related Hypermotor Epilepsy Deep Research Fallback

⚠️ Fallback MONDO:0000030

Familial Sleep-Related Hypermotor Epilepsy Deep Research Fallback

Provider Attempts

  • falcon: timeout --foreground 120s just research-disorder falcon Familial_Sleep_Related_Hypermotor_Epilepsy produced no usable content and was terminated with signal 15.
  • openai: timeout --foreground 120s just research-disorder openai Familial_Sleep_Related_Hypermotor_Epilepsy produced no usable content and was terminated with signal 15.

Because the preferred deep-research providers did not return usable content in bounded attempts, this fallback records the literature scope used for curation. All YAML evidence was taken from generated Orphanet and PubMed reference caches, not from hand-created reference text.

Literature Scope

Familial sleep-related hypermotor epilepsy corresponds to MONDO:0000030 and Orphanet ORPHA:98784. The Orphanet record provides the structured definition, autosomal dominant inheritance, gene rows for CABP4, CHRNA2, CHRNA4, CHRNB2, CRH, DEPDC5, and KCNT1, and the HPO phenotype-frequency table used for frequency-backed phenotype entries.

The clinical scope was anchored with the GeneReviews ADSHE chapter and the Neurology consensus definition paper. Those sources support the modern sleep-related hypermotor epilepsy terminology, diagnostic certainty levels based on witnessed, video-documented, and video-EEG-documented events, genetic testing across the heterogeneous ADSHE gene set, non-progressive but lifelong course, carbamazepine-centered therapy, genotype-informed alternatives, VNS, and genetic counseling.

Mechanistic curation focused on three evidence-backed branches. CHRNA4, CHRNB2, and CHRNA2 studies support nicotinic acetylcholine receptor dysfunction with altered receptor efficacy or loss of function. DEPDC5 evidence supports loss-of-function variants in ADNFLE families and GATOR1/mTORC1 dysregulation in model systems. KCNT1 evidence supports altered Slack-channel effects on cortical neuronal excitability. These branches converge on cortical excitation-inhibition imbalance and sleep-related hypermotor seizure expression.

Curation Decisions

  • Used MONDO:0000030 as the disease term because the ORPHA record title is broader and its MONDO cross-reference points to an obsolete identifier.
  • Included all ORPHA very frequent and frequent HPO phenotypes: nocturnal seizures, paroxysmal dystonia, involuntary movements, and motor stereotypy.
  • Retained additional occasional ORPHA phenotypes when clinically coherent for SHE semiology or diagnosis: focal hyperkinetic seizure, interictal epileptiform activity, and urinary incontinence.
  • Modeled the five MONDO/OMIM ENFL subtypes as root subtypes, and added a DEPDC5-related SHE subtype because Orphanet and human family sequencing both support DEPDC5 loss-of-function in SHE/ADNFLE presentations.
  • Did not force individual mechanistic branches for CABP4 or CRH because the available curated evidence was sufficient to record them as genetic heterogeneity but not enough for a distinct mechanism node.