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ORPHA:289494

4H leukodystrophy

high confidenceDisorder

Also known as: POLR-related leukodystrophy

Publications

138

59.9th percentile

Trials

0

Interventional, condition-specific

Researchers

1,224

Distinct authors in sample

Gene link

—

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare hypomyelinating leukodystrophy disorder characterized by the association of dental abnormalities (delayed dentition, abnormal order of dentition, hypodontia), hypogonadotropic hypogonadism, and hypomyelinating leukodystrophy manifesting with neurodevelopmental delay or regression and/or cerebellar symptoms.

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

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

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 specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedNot found

    No GenCC disease–gene assertion in this build

  2. LiteraturePresent

    138 matched papers (122 in last 10 years) Source

  3. Phenotype characterisedPresent

    217 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 trialPartial

    None under the specific name; 31 for broader category leukodystrophy

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?

Not yet — the cause hasn't been pinned down in GenCC.

No strong gene–disease assertion joined for this Orphanet entity.

Phenotypes (Monarch / HPO)

217

Associated phenotypes · MONDO:0100605

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

Showing 5 of 217 — 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?

138

138 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

138 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).

122 in the last 10 years · high confidence · 59.9th percentile (publications denominator)

Phrase hits: 138 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,224

Distinct author names in 138 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
    Bernard G51 papers · 2025

    Departments of Neurology and Neurosurgery, and Pediatrics, McGill University, Montreal, Canada.

    Papers in Europe PMC
  2. 02
    Wolf NI21 papers · 2025

    Department of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands.

    Papers in Europe PMC
  3. 03
    Vanderver A16 papers · 2025

    1] Center for Genetic Medicine Research, Children's National, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010, USA. [2] Department of Neurology, Children's National, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010, USA. [3] George Washington University, School of Medicine, Washington, District of Columbia 20052, USA.

    Papers in Europe PMC
  4. 04
    Guerrero K13 papers · 2024

    Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.

    Papers in Europe PMC
  5. 05
    Tran LT13 papers · 2024

    Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.

    Papers in Europe PMC
  6. 06
    van der Knaap MS12 papers · 2024

    Department of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands.

    Papers in Europe PMC
  7. 07
    Perrier S11 papers · 2025

    Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.

    Papers in Europe PMC
  8. 08
    Thiffault I11 papers · 2024

    1] Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada. [2] Service de Génétique, Centre Hospitalier Universitaire Sainte-Justine, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec H3T1C5, Canada. [3] Center for Pediatric Genomic Medicine, Children's Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, Missouri 64108, USA.

    Papers in Europe PMC
  9. 09
    Brais B9 papers · 2025

    Montreal Neurological Institute, McGill University, 3801 University Street, room 622, Montréal, Québec, H3A 2B4, Canada. bernard.brais@mcgill.ca.

    Papers in Europe PMC
  10. 10
    Coulombe B8 papers · 2024

    Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.

    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). 31 trials are registered for leukodystrophy, 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.

high 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.

31 interventional trials matched leukodystrophy, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: leukodystrophy

31

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.

Recruiting under the broader category

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 4H leukodystrophy — 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.

"4H leukodystrophy" OR "POLR-related leukodystrophy"

Run this search on Europe PMC

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

"4H leukodystrophy" OR "POLR-related leukodystrophy"

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

Parent-category trials query:

"leukodystrophy"

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

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-27T12:13:59.263Z