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ORPHA:275543

L1 syndrome

low confidenceDisorder

Also known as: CRASH syndrome · Corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome · L1CAM syndrome

Publications

8,627

Trials

0

Interventional, condition-specific

Researchers

1,217

Distinct authors in sample

Gene link

L1CAM

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare, X-linked developmental disorder characterized by hydrocephalus of varying degrees of severity, intellectual deficit, spasticity of the legs, and adducted thumbs. The syndrome represents a spectrum of disorders including: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, X-linked complicated spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis.

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.

Additional Mondo synonyms (1)

corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus 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

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 — L1CAM

  2. LiteraturePresent

    8,627 matched papers (6,144 in last 10 years) Source

  3. Phenotype characterisedPresent

    107 HPO annotations (e.g. Spastic paraplegia; Mild intellectual disability; Moderate intellectual disability) Source

  4. Animal modelPresent

    1 genotype model (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 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 (L1CAM).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

107

Associated phenotypes · MONDO:0017140

  • Spastic paraplegia
  • Mild intellectual disability
  • Moderate intellectual disability
  • Upper motor neuron dysfunction
  • Lower limb muscle weakness

Showing 5 of 107 — 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?

8,627

8,627 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

8,627 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).

6,144 in the last 10 years · low confidence

Phrase hits: 298 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,217

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
    Schachner M17 papers · 2025

    Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, China.

    Papers in Europe PMC
  2. 02
    Loers G9 papers · 2024

    Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

    Papers in Europe PMC
  3. 03
    Kleene R8 papers · 2024

    Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

    Papers in Europe PMC
  4. 04
    Maness PF7 papers · 2023

    Department of Biochemistry and Biophysics, and Carolina Institute of Developmental Disabilities, University of North Carolina, School of Medicine at Chapel Hill, United States. Electronic address: srclab@med.unc.edu.

    Papers in Europe PMC
  5. 05
    Vos YJ6 papers · 2013

    Department of Genetics, University Medical Centre Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. y.j.vos@medgen.umcg.nl

    Papers in Europe PMC
  6. 06
    Kanemura Y5 papers · 2026

    Institute for Clinical Research and Department of Neurosurgery, Osaka National Hospital, Osaka, Japan.

    Papers in Europe PMC
  7. 07
    Ben-Ze'ev A4 papers · 2023

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.

    Papers in Europe PMC
  8. 08
    Congiu L4 papers · 2024

    Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.

    Papers in Europe PMC
  9. 09
    Duncan BW4 papers · 2023

    Department of Biochemistry and Biophysics, and Carolina Institute of Developmental Disabilities, University of North Carolina, School of Medicine at Chapel Hill, United States.

    Papers in Europe PMC
  10. 10
    Fransen E4 papers · 1998

    Department of Medical Genetics, University of Antwerp, Belgium.

    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 43 · after dedupe 43 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 43 · 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).

Uncertain / not reviewed (43)

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 L1 syndrome — 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.

("L1 syndrome" OR "CRASH syndrome" OR "Corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome" OR "L1CAM syndrome") OR ("L1CAM" OR "L1CAM-related" OR "L1-related")

Run this search on Europe PMC

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

"L1 syndrome" OR "CRASH syndrome" OR "Corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome" OR "L1CAM syndrome"

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 short or not clearly distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (8627) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-27T11:36:38.520Z