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ORPHA:464282

Spastic paraplegia-severe developmental delay-epilepsy syndrome

low confidenceDisorder

Also known as: SPPRS syndrome · Spastic paraplegia-psychomotor retardation-seizures syndrome

Publications

871

Trials

0

Interventional, condition-specific

Researchers

14

Distinct authors in sample

Gene link

HACE1

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Spastic paraplegia-severe - syndrome is a rare, genetic, complex spastic paraplegia disorder characterized by an -onset of psychomotor with severe and poor speech acquisition, associated with (mostly myoclonic), muscular which may be noted at birth, and slowly spasticity in the lower limbs leading to severe gait disturbances. Ocular abnormalities and incontinence are commonly associated. Other symptoms may include verbal dyspraxia, hypogenitalism, macrocephaly and sensorineural hearing loss, as well as dystonic movements and with upper limb involvement.

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 (1)

spastic paraplegia-psychomotor retardation-seizures 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 specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Definitive — HACE1

  2. LiteraturePresent

    871 matched papers (671 in last 10 years) Source

  3. Phenotype characterisedPresent

    68 HPO annotations (e.g. Hypertelorism; Sensorineural hearing impairment; Deeply set eye) 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 trialPartial

    None under the specific name; 1435 for broader category epilepsy

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 (HACE1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

68

Associated phenotypes · MONDO:0014764

  • Hypertelorism
  • Sensorineural hearing impairment
  • Deeply set eye
  • Myopia
  • Ataxia

Showing 5 of 68 — 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?

871

871 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.

871 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).

671 in the last 10 years · low confidence

Phrase hits: 1 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

14

Distinct author names in 1 sampled paper — 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
    Beltran S1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: sergi.beltran@cnag.crg.eu.

    Papers in Europe PMC
  2. 02
    Bullich G1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

    Papers in Europe PMC
  3. 03
    Gut I1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

    Papers in Europe PMC
  4. 04
    Horvath R1 paper · 2020

    Department of Clinical Neurosciences, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.

    Papers in Europe PMC
  5. 05
    Laurie S1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

    Papers in Europe PMC
  6. 06
    Lochmüller H1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; Department of Medicine, Division of Neurology, Children's Hospital of Eastern Ontario Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.

    Papers in Europe PMC
  7. 07
    Matalonga L1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

    Papers in Europe PMC
  8. 08
    Mereu E1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

    Papers in Europe PMC
  9. 09
    Papakonstantinou A1 paper · 2020

    Centro Nacional de Análisis Genómico (CNAG)-Centro de Regulación Genómica (CRG), Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

    Papers in Europe PMC
  10. 10
    Pérez-Jurado L1 paper · 2020

    Hospital del Mar Research Institute (IMIM), Barcelona, Spain; Hospital del Mar Research Institute (IMIM) and Centro de Investigación Biomédica en Red-Enfermedades Raras (CIBERER), Barcelona, Spain; Women's and Children Hospital, South Australian Health and Medical Research Institute and The University of Adelaide, Adelaide, South Australia, Australia.

    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). 1,435 trials are registered for epilepsy, 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.

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.

1,435 interventional trials matched epilepsy, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: epilepsy

1,435

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

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 Spastic paraplegia-severe developmental delay-epilepsy 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.

("Spastic paraplegia-severe developmental delay-epilepsy syndrome" OR "SPPRS syndrome" OR "Spastic paraplegia-psychomotor retardation-seizures syndrome") OR ("HACE1" OR "HACE1 syndrome" OR "HACE1-related")

Run this search on Europe PMC

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

"Spastic paraplegia-severe developmental delay-epilepsy syndrome" OR "SPPRS syndrome" OR "Spastic paraplegia-psychomotor retardation-seizures syndrome"

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

Parent-category trials query:

"epilepsy"

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

Ingested 2026-07-27T16:54:04.151Z