RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:391376

Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome

low confidenceDisorder

Also known as: Asparagine synthetase deficiency

Publications

3,980

Trials

1

Interventional, condition-specific

Researchers

642

Distinct authors in sample

Gene link

ASNS

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic, neurometabolic disorder characterized by severe, microcephaly, severe to profound global development delay, , (typically tonic and/or myoclonic and frequently intractable), hyperekplexia, and axial with appendicular spasticity, as well as hyperreflexia, dyskinetic quadriplegia, and abnormal brain morphology (cerebral atrophy with variable additional features including ventriculomeglay, pons and/or cerebellar hypoplasia, simplified gyral pattern and delayed myelination). Cortical blindness, feeding difficulties and respiratory insufficiency 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 (2)

asparagine synthetase deficiency · congenital microcephaly - severe encephalopathy - progressive cerebral atrophy 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

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — ASNS

  2. LiteraturePresent

    3,980 matched papers (2,965 in last 10 years) Source

  3. Phenotype characterisedPresent

    58 HPO annotations (e.g. Hypotonia; Gastroesophageal reflux; Thin corpus callosum) 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 trialPresent

    1 matched on ClinicalTrials.gov (1 recruiting in sample)

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 (ASNS).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

58

Associated phenotypes · MONDO:0014258

  • Hypotonia
  • Gastroesophageal reflux
  • Thin corpus callosum
  • Hypertelorism
  • Cortical dysplasia

Showing 5 of 58 — 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?

3,980

3,980 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.

3,980 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).

2,965 in the last 10 years · low confidence

Phrase hits: 87 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

642

Distinct author names in 87 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Kilberg MS10 papers · 2023

    Department of Biochemistry & Molecular Biology, University of Florida College of Medicine, 1200 Newell Drive, Florida, USA, 32608.

    Papers in Europe PMC
  2. 02
    Alfadhel M6 papers · 2020

    Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

    Papers in Europe PMC
  3. 03
    Staklinski SJ6 papers · 2023

    Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, Florida, USA.

    Papers in Europe PMC
  4. 04
    Sun Y5 papers · 2024

    BGI Genomics, BGI-Shenzhen, 518083, Shenzhen, China.

    Papers in Europe PMC
  5. 05
    Wang X5 papers · 2024

    Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, China.

    Papers in Europe PMC
  6. 06
    Blau N4 papers · 2026

    Division of Metabolism, University Children's Hospital, Zürich, Switzerland. Electronic address: nenad.blau@kispi.uzh.ch.

    Papers in Europe PMC
  7. 07
    Chang MC4 papers · 2023

    Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, Florida, USA.

    Papers in Europe PMC
  8. 08
    Eyaid W4 papers · 2020

    Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

    Papers in Europe PMC
  9. 09
    Merritt ME4 papers · 2023

    Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, Florida, USA.

    Papers in Europe PMC
  10. 10
    Wang Y4 papers · 2024

    The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, 116044, P.R. China. tcwyice@163.com.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

1

interventional trials for this specific condition

1 interventional trial matched this specific condition name; 1 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

1 interventional trial — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 80.1th percentile).

low confidence · 80.1th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

1 interventional trials matched after quoted-phrase search and title/condition post-filter.

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 Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy 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.

("Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome" OR "Asparagine synthetase deficiency" OR "congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome") OR ("ASNS" OR "ASNS syndrome" OR "ASNS-related")

Run this search on Europe PMC

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

"Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome" OR "Asparagine synthetase deficiency" OR "congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 1 interventional · 1 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 multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (3980) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T15:03:45.163Z