RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:313772

Early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome

low confidenceDisorder

Also known as: AFG3L2-related spastic ataxia-myoclonic epilepsy-neuropathy syndrome · Autosomal recessive spastic ataxia type 5 · SPAX5

Publications

1,139

Trials

0

Interventional, condition-specific

Researchers

1,026

Distinct authors in sample

Gene link

AFG3L2

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Early-onset spastic -myoclonic - syndrome is a rare spastic disorder characterized by childhood onset of slowly lower limb spastic paraparesis and cerebellar (with dysarthria, swallowing difficulties, motor degeneration), associated with sensorimotor (including muscle weakness and distal amyotrophy in lower extremities) and myoclonic . Ocular signs (ptosis, oculomotor apraxia), dysmetria, dysdiadochokinesia, dystonic movements and myoclonus may also be associated.

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)

AFG3L2 autosomal recessive spastic ataxia · AFG3L2-related spastic ataxia-neuropathy syndrome · autosomal recessive spastic ataxia caused by mutation in AFG3L2 · autosomal recessive spastic ataxia type 5 · spastic ataxia type 5

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 — AFG3L2

  2. LiteraturePresent

    1,139 matched papers (845 in last 10 years) Source

  3. Phenotype characterisedPresent

    45 HPO annotations (e.g. Cognitive impairment; Spastic paraparesis; Spasticity) 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; 3 for broader category spastic ataxia

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 (AFG3L2).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

45

Associated phenotypes · MONDO:0013776

  • Cognitive impairment
  • Spastic paraparesis
  • Spasticity
  • Myoclonus
  • Cerebellar atrophy

Showing 5 of 45 — 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?

1,139

1,139 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.

1,139 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).

845 in the last 10 years · low confidence

Phrase hits: 139 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,026

Distinct author names in 139 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 L9 papers · 2025

    German Center for Neurodegenerative Disease (DZNE), 72076 Tübingen, Germany; Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research & Center of Neurology, University of Tübingen, 72076 Tübingen, Germany.

    Papers in Europe PMC
  2. 02
    Wang Y8 papers · 2024

    Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. College of Medicine, Swansea University, Swansea, United Kingdom. Translational Medicine, GlaxoSmithKline R&D China, Addenbrookes Hospital, Cambridge, United Kingdom. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom. Willink Biochemical Genetics Unit, Genetic Medicine, St. Mary’s Hospital, Manchester, United Kingdom. Paediatric Neurology and Department of Ophthalmology, Barts Health NHS Trust, London, United Kingdom. Scientific Institute IRCCS Eugenio Medea, Conegliano Research Centre, Conegliano, Italy. Scientific Institute IRCCS Eugenio Medea, Laboratory of Molecular Biology, Lecco, Italy. Tokyo Medical University, Ibaraki Medical Center, Ami Ibaraki, Japan. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. Junshin Clinic, Bile Acid Institute, Tokyo, Japan. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tubingen, Tubingen, Germany. German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany. Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland. Neurology, University Hospital Basel, Basel, Switzerland. Rare Neurological Diseases Unit, Department of Neurology, University Hospital “Attikon,” Medical School of the University of Athens, Athens, Greece. Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA. Department of Biosciences and Nutrition, Center for Biosciences, Stockholm, Sweden. Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.

    Papers in Europe PMC
  3. 03
    Griffiths WJ7 papers · 2024

    Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. College of Medicine, Swansea University, Swansea, United Kingdom. Translational Medicine, GlaxoSmithKline R&D China, Addenbrookes Hospital, Cambridge, United Kingdom. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom. Willink Biochemical Genetics Unit, Genetic Medicine, St. Mary’s Hospital, Manchester, United Kingdom. Paediatric Neurology and Department of Ophthalmology, Barts Health NHS Trust, London, United Kingdom. Scientific Institute IRCCS Eugenio Medea, Conegliano Research Centre, Conegliano, Italy. Scientific Institute IRCCS Eugenio Medea, Laboratory of Molecular Biology, Lecco, Italy. Tokyo Medical University, Ibaraki Medical Center, Ami Ibaraki, Japan. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. Junshin Clinic, Bile Acid Institute, Tokyo, Japan. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tubingen, Tubingen, Germany. German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany. Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland. Neurology, University Hospital Basel, Basel, Switzerland. Rare Neurological Diseases Unit, Department of Neurology, University Hospital “Attikon,” Medical School of the University of Athens, Athens, Greece. Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA. Department of Biosciences and Nutrition, Center for Biosciences, Stockholm, Sweden. Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.

    Papers in Europe PMC
  4. 04
    De Michele G6 papers · 2023

    Department of Neuroscience and Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy.

    Papers in Europe PMC
  5. 05
    Fu Y6 papers · 2025

    Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, Fujian Medical University, Fuzhou, 350005, China. fuying@fjmu.edu.cn.

    Papers in Europe PMC
  6. 06
    Goizet C6 papers · 2023

    University Bordeaux, Equipe « Neurogénétique Translationnelle - NRGEN », INCIA CNRS UMR5287 Université Bordeaux and Centre de Reference Maladies Rares « Neurogénétique », Service de Génétique Médicale, Bordeaux University Hospital (CHU Bordeaux), 33000 Bordeaux, France.

    Papers in Europe PMC
  7. 07
    Hauser S6 papers · 2025

    Center for Neurology and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University, 72076 Tübingen, Germany.

    Papers in Europe PMC
  8. 08
    Liu Y6 papers · 2025

    Department of Preventive Dentistry, Peking University School and Hospital of Stomatology and National Center of Stomatology and National Clinical Research Center for Oral Diseases and National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.

    Papers in Europe PMC
  9. 09
    Maltecca F6 papers · 2026

    Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

    Papers in Europe PMC
  10. 10
    Schüle R6 papers · 2024

    Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, 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). 3 trials are registered for spastic ataxia, 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.

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

Broader category: spastic ataxia

3

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 Early-onset spastic ataxia-myoclonic epilepsy-neuropathy 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.

("Early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome" OR "AFG3L2-related spastic ataxia-myoclonic epilepsy-neuropathy syndrome" OR "Autosomal recessive spastic ataxia type 5" OR "SPAX5" OR "AFG3L2 autosomal recessive spastic ataxia" OR "AFG3L2-related spastic ataxia-neuropathy syndrome" OR "autosomal recessive spastic ataxia caused by mutation in AFG3L2" OR "spastic ataxia type 5") OR ("AFG3L2" OR "AFG3L2 syndrome" OR "AFG3L2-related")

Run this search on Europe PMC

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

"Early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome" OR "AFG3L2-related spastic ataxia-myoclonic epilepsy-neuropathy syndrome" OR "Autosomal recessive spastic ataxia type 5" OR "SPAX5" OR "AFG3L2 autosomal recessive spastic ataxia" OR "AFG3L2-related spastic ataxia-neuropathy syndrome" OR "autosomal recessive spastic ataxia caused by mutation in AFG3L2" OR "spastic ataxia type 5"

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

Parent-category trials query:

"spastic ataxia"

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 (1139) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T12:58:32.687Z