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ORPHA:481152

PYCR2-related microcephaly-progressive leukoencephalopathy

low confidenceDisorder

Publications

585

Trials

0

Interventional, condition-specific

Researchers

371

Distinct authors in sample

Gene link

PYCR2

Definitive

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

PYCR2-related microcephaly- leukoencephalopathy is a rare, genetic, syndromic disorder characterized by postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial , appendicular with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and . Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders.

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)

HLD10 · PYCR2 leukodystrophy · hypomyelinating leukodystrophy type 10 · leukodystrophy caused by mutation in PYCR2 · leukodystrophy, hypomyelinating, 10 · leukodystrophy, hypomyelinating, type 10

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.”

3/6 stages with a signal

No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.

  1. Gene identifiedPresent

    Definitive — PYCR2

  2. LiteraturePresent

    585 matched papers (492 in last 10 years) Source

  3. Phenotype characterisedPresent

    99 HPO annotations (e.g. Long philtrum; Anteverted nares; Hypoplasia of the brainstem) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  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 (PYCR2).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

99

Associated phenotypes · MONDO:0018825

  • Long philtrum
  • Anteverted nares
  • Hypoplasia of the brainstem
  • Cerebral cortical atrophy
  • Short nose

Showing 5 of 99 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

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?

585

585 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.

585 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).

492 in the last 10 years · low confidence

Phrase hits: 37 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

371

Distinct author names in 37 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
    Distelmaier F3 papers · 2023

    Department of General Pediatrics, Neonatology and Pediatric Cardiology University Children's Hospital Medical Faculty Heinrich-Heine-University Düsseldorf Mooren str. 540225 Düsseldorf Germany.

    Papers in Europe PMC
  2. 02
    Mayatepek E3 papers · 2023

    Department of General Pediatrics, Neonatology and Pediatric Cardiology University Children's Hospital Medical Faculty Heinrich-Heine-University Düsseldorf Mooren str. 540225 Düsseldorf Germany.

    Papers in Europe PMC
  3. 03
    Yamauchi J3 papers · 2023

    Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.

    Papers in Europe PMC
  4. 04
    Calame DG2 papers · 2022

    Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

    Papers in Europe PMC
  5. 05
    Clarke CF2 papers · 2020

    Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, USA. Electronic address: cathy@chem.ucla.edu.

    Papers in Europe PMC
  6. 06
    Gleeson JG2 papers · 2018

    Departments of Neurosciences and Pediatrics, Howard Hughes Medical Institute, University of California San Diego, Rady Children's Institute for Genomic Medicine, La Jolla, CA, 92093, USA.

    Papers in Europe PMC
  7. 07
    Herebian D2 papers · 2022

    Department of General Pediatrics, Neonatology and Pediatric Cardiology University Children's Hospital Medical Faculty Heinrich-Heine-University Düsseldorf Mooren str. 540225 Düsseldorf Germany.

    Papers in Europe PMC
  8. 08
    Hirano M2 papers · 2012

    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.

    Papers in Europe PMC
  9. 09
    Laugwitz L2 papers · 2023

    Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.

    Papers in Europe PMC
  10. 10
    Li M2 papers · 2024

    Department of Pediatrics, Peking University First Hospital, Beijing, China.

    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).

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.

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 PYCR2-related microcephaly-progressive leukoencephalopathy — 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.

("PYCR2-related microcephaly-progressive leukoencephalopathy" OR "HLD10" OR "PYCR2 leukodystrophy" OR "hypomyelinating leukodystrophy type 10" OR "leukodystrophy caused by mutation in PYCR2" OR "leukodystrophy, hypomyelinating, 10" OR "leukodystrophy, hypomyelinating, type 10") OR ("PYCR2" OR "PYCR2 syndrome" OR "PYCR2-related")

Run this search on Europe PMC

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

"PYCR2-related microcephaly-progressive leukoencephalopathy" OR "HLD10" OR "PYCR2 leukodystrophy" OR "hypomyelinating leukodystrophy type 10" OR "leukodystrophy caused by mutation in PYCR2" OR "leukodystrophy, hypomyelinating, 10" OR "leukodystrophy, hypomyelinating, type 10"

Study-type breakdown: 0 interventional · 0 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

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (585) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T17:15:50.998Z