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ORPHA:1486

Lethal congenital contracture syndrome type 1

low confidenceDisorder

Also known as: Herva disease · LCCS1 · Multiple contracture syndrome, Finnish type

Publications

856

Trials

0

Interventional, condition-specific

Researchers

592

Distinct authors in sample

Gene link

GLE1

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Lethal contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.

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 (5)

GLE1 lethal congenital contracture syndrome · lethal congenital contracture syndrome 1 · lethal congenital contracture syndrome caused by mutation in GLE1 · lethal congenital contracture syndrome type 1 · multiple contracture syndrome, Finnish type

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

    Definitive — GLE1

  2. LiteraturePresent

    856 matched papers (504 in last 10 years) Source

  3. Phenotype characterisedPresent

    28 HPO annotations (e.g. Abnormality of the amniotic fluid; Abnormal thorax morphology; Skeletal muscle atrophy) Source

  4. Animal modelPresent

    1 genotype model (Danio rerio) 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 (GLE1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

28

Associated phenotypes · MONDO:0009670

  • Abnormality of the amniotic fluid
  • Abnormal thorax morphology
  • Skeletal muscle atrophy
  • Pulmonary hypoplasia
  • Widening of cervical spinal canal

Showing 5 of 28 — open Monarch for the full list.

Animal models (Monarch / Alliance)

1

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?

856

856 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.

856 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).

504 in the last 10 years · low confidence

Phrase hits: 97 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

592

Distinct author names in 97 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
    Wente SR13 papers · 2020

    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.

    Papers in Europe PMC
  2. 02
    Kuure S6 papers · 2026

    Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland.

    Papers in Europe PMC
  3. 03
    Aditi5 papers · 2019

    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.

    Papers in Europe PMC
  4. 04
    Folkmann AW5 papers · 2015

    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.

    Papers in Europe PMC
  5. 05
    Hinttala R5 papers · 2025

    Research Unit of Clinical Medicine and Medical Research Center, Oulu University Hospital and University of Oulu, 90014 Oulu, Finland.

    Papers in Europe PMC
  6. 06
    Sipilä P4 papers · 2025

    Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, 20014 Turku, Finland.

    Papers in Europe PMC
  7. 07
    Zárybnický T4 papers · 2026

    Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland.

    Papers in Europe PMC
  8. 08
    Bolger TA3 papers · 2017

    Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, 465 21st Avenue South, Nashville, TN 37232-8240, USA.

    Papers in Europe PMC
  9. 09
    Dawson TR3 papers · 2019

    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240-7935, USA.

    Papers in Europe PMC
  10. 10
    Denecke J3 papers · 2019

    Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany.

    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.

Broader category lethal congenital contracture syndrome also has no matched interventional trial. See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.

Broader category: lethal congenital contracture syndrome

0

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Parent-category matching found a broader label but no interventional trials under it. How we count trials.

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 Lethal congenital contracture syndrome type 1 — 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.

("Lethal congenital contracture syndrome type 1" OR "Herva disease" OR "LCCS1" OR "Multiple contracture syndrome, Finnish type" OR "GLE1 lethal congenital contracture syndrome" OR "lethal congenital contracture syndrome 1" OR "lethal congenital contracture syndrome caused by mutation in GLE1") OR ("GLE1" OR "GLE1 syndrome" OR "GLE1-related")

Run this search on Europe PMC

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

"Lethal congenital contracture syndrome type 1" OR "Herva disease" OR "LCCS1" OR "Multiple contracture syndrome, Finnish type" OR "GLE1 lethal congenital contracture syndrome" OR "lethal congenital contracture syndrome 1" OR "lethal congenital contracture syndrome caused by mutation in GLE1"

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

Parent-category trials query:

"lethal congenital contracture syndrome"

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

Ingested 2026-07-26T17:31:42.380Z