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ORPHA:100985

Autosomal dominant spastic paraplegia type 4

medium confidenceDisorder

Also known as: SPG4

Publications

1,450

87th percentile

Trials

0

Interventional, condition-specific

Researchers

641

Distinct authors in sample

Gene link

SPAST

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A rare form of spastic paraplegia with high intrafamilial clinical variability, characterized in most cases as a pure with an adult onset (mainly the 3rd to 5th decade of life, but that can present at any age) of gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex is also reported with additional manifestations including cognitive impairment, cerebellar , and . A faster disease progression is noted in patients with a later age of onset.

How rare: 1-9 / 1 000 000 — roughly one to nine people per million. In a city the size of Kolkata, perhaps a few dozen.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (5)

SPAST hereditary spastic paraplegia · autosomal dominant spastic paraplegia type 4 · hereditary spastic paraplegia 4 · hereditary spastic paraplegia caused by mutation in SPAST · hereditary spastic paraplegia type 4

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.”

5/6 stages with a signal

No specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Definitive — SPAST

  2. LiteraturePresent

    1,450 matched papers (928 in last 10 years) Source

  3. Phenotype characterisedPresent

    41 HPO annotations (e.g. Urinary urgency; Spasticity; Lower limb spasticity) Source

  4. Animal modelPresent

    5 genotype models (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 trialPartial

    None under the specific name; 104 for broader category paraplegia

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 (SPAST).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

41

Associated phenotypes · MONDO:0008438

  • Urinary urgency
  • Spasticity
  • Lower limb spasticity
  • Impaired vibration sensation at ankles
  • Pes cavus

Showing 5 of 41 — open Monarch for the full list.

Animal models (Monarch / Alliance)

5

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?

1,450

1,450 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.

1,450 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).

928 in the last 10 years · medium confidence · 87th percentile (publications denominator)

Phrase hits: 93 · MeSH hits: 1

Open Europe PMC search

Who's working on it?

641

Distinct author names in 94 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
    Schöls L10 papers · 2026

    German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany; Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. Electronic address: ludger.schoels@uni-tuebingen.de.

    Papers in Europe PMC
  2. 02
    Rattay TW9 papers · 2026

    Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.

    Papers in Europe PMC
  3. 03
    Schüle R9 papers · 2026

    German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany; Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.

    Papers in Europe PMC
  4. 04
    González-Salazar C4 papers · 2026

    Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.

    Papers in Europe PMC
  5. 05
    Hengel H4 papers · 2026

    Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.

    Papers in Europe PMC
  6. 06
    Kessler C4 papers · 2026

    Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.

    Papers in Europe PMC
  7. 07
    Völker M4 papers · 2023

    Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, and Center for Neurology, University of Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.

    Papers in Europe PMC
  8. 08
    Baas PW3 papers · 2026

    Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA pbaas@drexelmed.edu.

    Papers in Europe PMC
  9. 09
    Guillaud-Bataille M3 papers · 2025

    Département de génétique médicale, AP-HP, Sorbonne Université, UF de Neurogénétique Moléculaire et Cellulaire, CGMC, Hôpital Pitié-Salpêtrière, Paris, France.

    Papers in Europe PMC
  10. 10
    Liu Y3 papers · 2024

    State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (RRBGL), Inner Mongolia University, Hohhot, 010070, 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. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial. 104 trials are registered for paraplegia, the broader category — shown separately because they may or may not enrol this specific subtype.

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.

medium 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.

104 interventional trials matched paraplegia, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: paraplegia

104

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

Worth raising with a clinician. How we count trials.

Recruiting under the broader category

Observational and natural-history studies

1 observational study matches 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.

None of the matched observational studies is currently listed as 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 2026-07-30

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 Autosomal dominant spastic paraplegia type 4 — 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.

("Autosomal dominant spastic paraplegia type 4" OR "SPAST hereditary spastic paraplegia" OR "hereditary spastic paraplegia 4" OR "hereditary spastic paraplegia caused by mutation in SPAST" OR "hereditary spastic paraplegia type 4") OR (MESH:"Spastic paraplegia 4, autosomal dominant") OR ("SPAST" OR "SPAST syndrome" OR "SPAST-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Spastic paraplegia 4, autosomal dominant

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

"Autosomal dominant spastic paraplegia type 4" OR "SPAST hereditary spastic paraplegia" OR "hereditary spastic paraplegia 4" OR "hereditary spastic paraplegia caused by mutation in SPAST" OR "hereditary spastic paraplegia type 4" OR "Spastic paraplegia 4, autosomal dominant"

Study-type breakdown: 0 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"paraplegia"

Query health: ok — strategies attempted: phrase, mesh; with hits: phrase, mesh

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: SPG4

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

Ingested 2026-07-27T07:08:22.662Z