RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:137639

Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome

low confidenceSubtype of disorder

Also known as: Ataxia-delayed dentition-hypomyelination syndrome

Publications

1,172

Trials

0

Interventional, condition-specific

Researchers

1,059

Distinct authors in sample

Gene link

POLR3A

Strong

Readiness

4/6

Stages with a signal

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)

4H syndrome · HLD7 · hypomyelinating leukodystrophy 7 with or without oligodontia and-or hypogonadotropic hypogonadism · leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism · leukodystrophy, hypomyelinating, with hypodontia and hypogonadotropic hypogonadism · leukoencephalopathy, hypomyelinating, with ataxia and delayed dentition

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.”

4/6 stages with a signal

No matched interventional trial, but a gene association and an animal model are on record — often described as translation-ready / stalled at the clinical step.

  1. Gene identifiedPresent

    Strong — POLR3A

  2. LiteraturePresent

    1,172 matched papers (890 in last 10 years) Source

  3. Phenotype characterisedPresent

    72 HPO annotations (e.g. Hypogonadotropic hypogonadism; Ataxia; Vertical supranuclear gaze palsy) Source

  4. Animal modelPresent

    2 genotype models (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 trialNot found

    No matched interventional trial under our ClinicalTrials.gov rules

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 (POLR3A).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

72

Associated phenotypes · MONDO:0011897

  • Hypogonadotropic hypogonadism
  • Ataxia
  • Vertical supranuclear gaze palsy
  • Hypoplasia of the corpus callosum
  • Dysarthria

Showing 5 of 72 — open Monarch for the full list.

Animal models (Monarch / Alliance)

2

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?

1,172

1,172 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.

1,172 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).

890 in the last 10 years · low confidence

Phrase hits: 321 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,059

Distinct author names in 200 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
    Biederman J6 papers · 1993

    Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114.

    Papers in Europe PMC
  2. 02
    Rapport MD5 papers · 1997

    Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook School of Medicine 11794.

    Papers in Europe PMC
  3. 03
    Bernard G4 papers · 2020

    Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada; Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada. Electronic address: genevieve.bernard@mcgill.ca.

    Papers in Europe PMC
  4. 04
    Douglas VI4 papers · 1994

    Department of Psychology, McGill University, Montreal, Quebec, Canada.

    Papers in Europe PMC
  5. 05
    DuPaul GJ4 papers · 1994

    Department of Psychiatry, University of Massachusetts Medical Center, Worcester 01655.

    Papers in Europe PMC
  6. 06
    Halperin JM4 papers · 1994
    Papers in Europe PMC
  7. 07
    Newcorn JH4 papers · 1994

    Department of Psychiatry, Mount Sinai School of Medicine, New York, New York.

    Papers in Europe PMC
  8. 08
    Schachar R4 papers · 1990

    Department of Psychiatry, Hospital for Sick Children, Toronto, Ontario, Canada.

    Papers in Europe PMC
  9. 09
    Szatmari P4 papers · 1990

    Department of Psychiatry, Chedoke Child and Family Center, Chedoke-McMaster Hospitals, Hamilton, Ontario, Canada.

    Papers in Europe PMC
  10. 10
    Wolf NI4 papers · 2019

    Department of Child Neurology, VU University Medical Center and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands. Electronic address: n.wolf@vumc.nl.

    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. 2 observational studies did — shown below because natural-history and cohort work can be an important step toward a trial.

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.

See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.

Observational and natural-history studies

2 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

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 13 · after dedupe 13 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 13 · 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).

Uncertain / not reviewed (13)

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 Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination 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.

("Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome" OR "Ataxia-delayed dentition-hypomyelination syndrome" OR "4H syndrome" OR "hypomyelinating leukodystrophy 7 with or without oligodontia and-or hypogonadotropic hypogonadism" OR "leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism" OR "leukodystrophy, hypomyelinating, with hypodontia and hypogonadotropic hypogonadism" OR "leukoencephalopathy, hypomyelinating, with ataxia and delayed dentition") OR ("POLR3A" OR "POLR3A syndrome" OR "POLR3A-related")

Run this search on Europe PMC

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

"Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome" OR "Ataxia-delayed dentition-hypomyelination syndrome" OR "4H syndrome" OR "hypomyelinating leukodystrophy 7 with or without oligodontia and-or hypogonadotropic hypogonadism" OR "leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism" OR "leukodystrophy, hypomyelinating, with hypodontia and hypogonadotropic hypogonadism" OR "leukoencephalopathy, hypomyelinating, with ataxia and delayed dentition"

Study-type breakdown: 0 interventional · 2 observational · 0 expanded access. Only interventional studies enter the trial headline.

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

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: HLD7

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • "4H syndrome" also appears on ORPHA:88637
  • Publication count (1172) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T07:27:01.596Z