ORPHA:2478
Megalencephalic leukoencephalopathy with subcortical cysts
Also known as: MLC · Megalencephalic leukodystrophy · Megalencephaly-cystic leukodystrophy syndrome · Vacuolating megalencephalic leukoencephalopathy with subcortical cysts · Van der Knaap syndrome
Query health: suspect — Only one of 2 strategies returned hits (phrase).
Publications
534
Trials
0
Interventional, condition-specific
Researchers
1,104
Distinct authors in sample
Gene link
—
Readiness
1/6
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0011391
- MeSH:C536141
- UMLS:C1858854
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.”
1/6 stages with a signal
Research-stage checklist from open sources (GenCC, literature, Monarch when enriched, ClinicalTrials.gov). Not a prognosis or care recommendation.
- Gene identifiedNot found
No GenCC disease–gene assertion in this build
- LiteraturePresent
534 matched papers (290 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- 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)
Not enriched in this build — Monarch phenotype joins were not run for this record.
Animal models (Monarch / Alliance)
Not enriched in this build.
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=5449) is 41.
534 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).
290 in the last 10 years · low confidence
Phrase hits: 534 · MeSH hits: 0
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.
- 01van der Knaap MS21 papers · 2026
Department of Child Neurology Free University Medical Center Amsterdam, The Netherlands
Papers in Europe PMC - 02Ambrosini E16 papers · 2026
Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
Papers in Europe PMC - 03Brignone MS14 papers · 2026
Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
Papers in Europe PMC - 04Estévez 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 - 05Lanciotti A11 papers · 2026
Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
Papers in Europe PMC - 06Min R11 papers · 2026
Department of Child Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Papers in Europe PMC - 07Bertini 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 - 08Bugiani 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 - 09Elorza-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 - 10Mansvelder 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 27 July 2026
No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.
low confidence · 36.5th 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
- NCT03047369·RECRUITING·The Myelin Disorders Biorepository Project
Conditions: Leukodystrophy · White Matter Disease · Leukoencephalopathies · 4H Syndrome·Matched via name phrase
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
India — NPRD
Last verified 2026-07-26This 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"
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" OR "leukoencephalopathy, megalencephalic"
Recall-expansion terms: leukoencephalopathy, megalencephalic
Study-type breakdown: 0 interventional · 2 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: suspect — strategies attempted: phrase, recall-expansion; 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