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ORPHA:163985

Hyperekplexia-epilepsy syndrome

low confidenceDisorder

Publications

871

Trials

0

Interventional, condition-specific

Researchers

873

Distinct authors in sample

Gene link

ARHGEF9

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A rare, X-linked, syndromic disease characterized by which evolves to and an exaggerated startle response (to sudden visual, auditory or tactile stimuli), followed by the development of early-onset, frequently refractory, tonic or myoclonic . epileptic , , and psychomotor development arrest, with subsequent decline, may be additionally associated.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (6)

DEE8 · EIEE8 · developmental and epileptic encephalopathy 8 · epileptic encephalopathy, early infantile, 8 · epileptic encephalopathy, early infantile, type 8 · hyperekplexia-epilepsy syndrome

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

5/6 stages with a signal

No specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Definitive — ARHGEF9

  2. LiteraturePresent

    871 matched papers (558 in last 10 years) Source

  3. Phenotype characterisedPresent

    22 HPO annotations (e.g. Hypertonia; Exaggerated startle response; Developmental regression) Source

  4. Animal modelPresent

    1 genotype model (Mus musculus) Source

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. Interventional trialPartial

    None under the specific name; 1 for broader category hyperekplexia

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (ARHGEF9).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

22

Associated phenotypes · MONDO:0010375

  • Hypertonia
  • Exaggerated startle response
  • Developmental regression
  • Focal impaired awareness seizure
  • Hypoplasia of the frontal lobes

Showing 5 of 22 — open Monarch for the full list.

Animal models (Monarch / Alliance)

1

Model associations linked to this Mondo ID

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

871

871 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

871 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

558 in the last 10 years · low confidence

Phrase hits: 160 · MeSH hits: 1

Open Europe PMC search

Who's working on it?

873

Distinct author names in 161 sampled papers — named people below.

Who's working on it?

No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.

  1. 01
    Okada M5 papers · 2022

    Department of Neuropsychiatry, Division of Neuroscience, Graduate School of Medicine, Mie University, Tsu, Japan.

    Papers in Europe PMC
  2. 02
    Hauser WA4 papers · 2014
    Papers in Europe PMC
  3. 03
    Ottman R4 papers · 2014

    Department of Neurology, Columbia University, New York, USA.

    Papers in Europe PMC
  4. 04
    Vieira K4 papers · 2026

    Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY 10595, USA.

    Papers in Europe PMC
  5. 05
    Berg AT3 papers · 2021

    Department of Biology, Northern Illinois University, DeKalb, IL 60115, USA. atberg@niu.edu

    Papers in Europe PMC
  6. 06
    Chern CR3 papers · 2026

    Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY 10595, USA.

    Papers in Europe PMC
  7. 07
    Hirose S3 papers · 2019

    Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan. hirose@fukuoka-u.ac.jp

    Papers in Europe PMC
  8. 08
    Lerche H3 papers · 2010

    Department of Applied Physiology, University of Ulm, Germany. holger.lerche@medizin.uni-ulm.de

    Papers in Europe PMC
  9. 09
    Striano P3 papers · 2025

    Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

    Papers in Europe PMC
  10. 10
    Velíšek L3 papers · 2026

    Departments of Cell Biology & Anatomy, Pediatrics, and Neurology, New York Medical College, Valhalla, NY 10595, USA.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

0

interventional trials for this specific condition

No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present). 1 trial are registered for hyperekplexia, the broader category — shown separately because they may or may not enrol this specific subtype.

Data as of 11 September 2026 · last trial check 11 September 2026

No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.

low confidence · 38.6th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.

1 interventional trial matched hyperekplexia, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: hyperekplexia

1

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Worth raising with a clinician. How we count trials.

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-30

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Hyperekplexia-epilepsy syndrome — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("Hyperekplexia-epilepsy syndrome" OR "EIEE8" OR "developmental and epileptic encephalopathy 8" OR "epileptic encephalopathy, early infantile, 8" OR "epileptic encephalopathy, early infantile, type 8") OR (MESH:"Hyperekplexia and Epilepsy") OR ("ARHGEF9" OR "ARHGEF9 syndrome" OR "ARHGEF9-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Hyperekplexia and Epilepsy

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Hyperekplexia-epilepsy syndrome" OR "EIEE8" OR "developmental and epileptic encephalopathy 8" OR "epileptic encephalopathy, early infantile, 8" OR "epileptic encephalopathy, early infantile, type 8" OR "Hyperekplexia and Epilepsy"

Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"hyperekplexia"

Query health: ok — strategies attempted: phrase, mesh; with hits: phrase, mesh

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: DEE8

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (871) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T08:16:12.955Z