RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:466926

Seizures-scoliosis-macrocephaly syndrome

low confidenceDisorder

Also known as: SSM syndrome

Publications

4,799

Trials

0

Interventional, condition-specific

Researchers

510

Distinct authors in sample

Gene link

EXT2

Strong

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

-scoliosis-macrocephaly syndrome is a rare, genetic neurometabolic disorder characterized by , macrocephaly, delayed motor milestones, moderate , scoliosis with no exostoses, muscular present since birth, as well as renal dysfunction. Coarse facial features (including hypertelorism and long hypoplastic philtrum) and bilateral cryptorchidism (in males) are also commonly reported. Additional manifestations include abnormal gastrointestinal motility (resulting in constipation, diarrhea, gastroesophageal reflux and dysphagia), gait disturbances, strabismus and ventricular septal defects.

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 (2)

SSMS · seizures, scoliosis, and macrocephaly 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.”

3/6 stages with a signal

No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.

  1. Gene identifiedPresent

    Strong — EXT2

  2. LiteraturePresent

    4,799 matched papers (2,758 in last 10 years) Source

  3. Phenotype characterisedPresent

    70 HPO annotations (e.g. Poor speech; Strabismus; Moderate intellectual disability) 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 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 (EXT2).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

70

Associated phenotypes · MONDO:0014731

  • Poor speech
  • Strabismus
  • Moderate intellectual disability
  • Nail dysplasia
  • Encopresis

Showing 5 of 70 — 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?

4,799

4,799 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.

4,799 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).

2,758 in the last 10 years · low confidence

Phrase hits: 66 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

510

Distinct author names in 66 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
    Jaeken J3 papers · 2023

    Metabolic Center, Department of Pediatrics, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium.

    Papers in Europe PMC
  2. 02
    Li H3 papers · 2023

    BGI-Anhui Clinical Laboratory, BGI-Shenzhen, 236000, Fuyang, China.

    Papers in Europe PMC
  3. 03
    Li R3 papers · 2020

    Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, QC H3A 0G1, Canada.

    Papers in Europe PMC
  4. 04
    Wang J3 papers · 2025

    Department of Neurocritical Care, Inova Fairfax Hospital, Falls Church, VA, USA.

    Papers in Europe PMC
  5. 05
    Betti R2 papers · 2021

    Dermatology Clinic, Department of Health Sciences, University of Milan, Hospital San Paolo, 20142 Milan, Italy.

    Papers in Europe PMC
  6. 06
    Cerri A2 papers · 2021

    Dermatology Clinic, Department of Health Sciences, University of Milan, Hospital San Paolo, 20142 Milan, Italy.

    Papers in Europe PMC
  7. 07
    Ding L2 papers · 2020

    Department of the Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China.

    Papers in Europe PMC
  8. 08
    Dittberner T2 papers · 2005
    Papers in Europe PMC
  9. 09
    Francisco R2 papers · 2023

    UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Lisboa, Portugal.

    Papers in Europe PMC
  10. 10
    Freeze HH2 papers · 2021

    Human Genetics Program Sanford Children's Health Research Center Sanford, Burnham Prebys Medical Discovery Institute, La Jolla, CA.

    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 60 · after dedupe 57 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 57 · 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 (57)

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 Seizures-scoliosis-macrocephaly 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.

("Seizures-scoliosis-macrocephaly syndrome" OR "SSM syndrome" OR "seizures, scoliosis, and macrocephaly syndrome") OR ("EXT2" OR "EXT2 syndrome" OR "EXT2-related")

Run this search on Europe PMC

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

"Seizures-scoliosis-macrocephaly syndrome" OR "SSM syndrome" OR "seizures, scoliosis, and macrocephaly 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

Synonyms dropped by stoplist: SSMS

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
  • Publication count (4799) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T17:02:31.320Z