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ORPHA:2478

Megalencephalic leukoencephalopathy with subcortical cysts

low confidenceDisorder

Also known as: MLC · Megalencephalic leukodystrophy · Megalencephaly-cystic leukodystrophy syndrome · Vacuolating megalencephalic leukoencephalopathy with subcortical cysts · Van der Knaap syndrome

Publications

534

Trials

0

Interventional, condition-specific

Researchers

1,104

Distinct authors in sample

Gene link

—

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A form of leukodystrophy that is characterized by -onset macrocephaly, often with mild neurologic signs at presentation (such as mild motor delay), which worsen with time, leading to poor ambulation, falls, , spasticity, increasing and cognitive decline. Brain magnetic resonance imaging reveals diffusely abnormal and mildly swollen white matter as well as subcortical cysts in the anterior temporal and frontoparietal regions.

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 (3)

megalencephalic leukodystrophy · megalencephalic leukoencephalopathy with subcortical cysts type 1 · megalencephaly-cystic leukodystrophy 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.”

4/6 stages with a signal

Research-stage checklist from open sources (GenCC, literature, Monarch when enriched, ClinicalTrials.gov). Not a prognosis or care recommendation.

  1. Gene identifiedNot found

    No GenCC disease–gene assertion in this build

  2. LiteraturePresent

    534 matched papers (290 in last 10 years) Source

  3. Phenotype characterisedPresent

    57 HPO annotations (e.g. Seizure; Hypotonia; Motor delay) Source

  4. Animal modelPresent

    3 genotype models (Mus musculus) Source

  5. Orphan designationPartial

    1 EMA designation (none yet with FDA orphan-indication approval) — e.g. Adeno-associated virus of serotype rh10 encoding Human MLC1 under the control of GFAP promoter 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?

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

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

Phenotypes (Monarch / HPO)

57

Associated phenotypes · MONDO:0011391

  • Seizure
  • Hypotonia
  • Motor delay
  • Diffuse swelling of cerebral white matter
  • Diffuse white matter abnormalities

Showing 5 of 57 — open Monarch for the full list.

Animal models (Monarch / Alliance)

3

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)

1

Designation · no FDA orphan-indication approval yet

  • EMA Adeno-associated virus of serotype rh10 encoding Human MLC1 under the control of GFAP promoterTreatment of megalencephalic leukoencephalopathy with subcortical cysts · 15/10/2021 · PositiveEMA designation

Sources: FDA OOPD · EMA orphan designations

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?

534

534 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.

534 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).

290 in the last 10 years · low confidence

Phrase hits: 534 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,104

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
    van der Knaap MS21 papers · 2026

    Department of Child Neurology 
 Free University Medical Center 
 Amsterdam, The Netherlands

    Papers in Europe PMC
  2. 02
    Ambrosini E16 papers · 2026

    Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.

    Papers in Europe PMC
  3. 03
    Brignone MS14 papers · 2026

    Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.

    Papers in Europe PMC
  4. 04
    Estévez R13 papers · 2025

    Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. restevez@ub.edu.

    Papers in Europe PMC
  5. 05
    Lanciotti A11 papers · 2026

    Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.

    Papers in Europe PMC
  6. 06
    Min R11 papers · 2026

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

    Papers in Europe PMC
  7. 07
    Bertini E8 papers · 2026

    Unit of Neuromuscular and Neurodegenerative Disorders Laboratory of Molecular Medicine, Department of Neurosciences, Bambino Gesu' Children's Research Hospital, V.le S. Paolo, 15, Rome 00146, Italy.

    Papers in Europe PMC
  8. 08
    Bugiani M8 papers · 2026

    Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, 1105 AZ, The Netherlands.

    Papers in Europe PMC
  9. 09
    Elorza-Vidal X8 papers · 2021

    Unitat de Fisiologia, Departament de Ciències Fisiològiques, IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.

    Papers in Europe PMC
  10. 10
    Mansvelder HD8 papers · 2026

    Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.

    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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-29

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 Megalencephalic leukoencephalopathy with subcortical cysts — 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.

"Megalencephalic leukoencephalopathy with subcortical cysts" OR "Megalencephalic leukodystrophy" OR "Megalencephaly-cystic leukodystrophy syndrome" OR "Vacuolating megalencephalic leukoencephalopathy with subcortical cysts" OR "Van der Knaap syndrome" OR "megalencephalic leukoencephalopathy with subcortical cysts type 1"

Run this search on Europe PMC

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

"Megalencephalic leukoencephalopathy with subcortical cysts" OR "Megalencephalic leukodystrophy" OR "Megalencephaly-cystic leukodystrophy syndrome" OR "Vacuolating megalencephalic leukoencephalopathy with subcortical cysts" OR "Van der Knaap syndrome" OR "megalencephalic leukoencephalopathy with subcortical cysts type 1"

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: MLC

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 (534) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T20:16:46.590Z