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ORPHA:990

Agnathia-holoprosencephaly-situs inversus syndrome

low confidenceDisorder

Publications

12,113

Trials

0

Interventional, condition-specific

Researchers

1,238

Distinct authors in sample

Gene link

OTX2, PRRX1

Strong

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

An extremely rare and fatal association syndrome, characterized by absence of the mandible, cerebral malformations with facial anomalies related to a defect in cleavage in the embryonic brain (e.g. synophthalmia, malformed and low-set ears fused in midline (otocephaly), agenesis of the olfactory bulbs, microstomia, hypoglossia/aglossia) and situs inversus partialis or totalis.

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)

agnathia-holoprosencephaly-situs inversus syndrome · agnathia-otocephaly complex · dysgnathia complex agnathia-holoprosencephaly · holoprosencephaly-agnathia · otocephaly

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 matched interventional trial, but a gene association and an animal model are on record — often described as translation-ready / stalled at the clinical step.

  1. Gene identifiedPresent

    Strong — OTX2, PRRX1

  2. LiteraturePresent

    12,113 matched papers (8,174 in last 10 years) Source

  3. Phenotype characterisedPresent

    41 HPO annotations (e.g. Narrow mouth; Abnormal cranial nerve morphology; Respiratory distress) Source

  4. Animal modelPresent

    2 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 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 (OTX2, PRRX1).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

41

Associated phenotypes · MONDO:0008740

  • Narrow mouth
  • Abnormal cranial nerve morphology
  • Respiratory distress
  • Hypoplasia of penis
  • Microglossia

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

Animal models (Monarch / Alliance)

2

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)

1 associated chemical. Therapeutic evidence is listed first when present — not a treatment recommendation.

  • Aspirin · marker/mechanism

MyDisease.info · MONDO:0008740

Literature

Is anyone studying this?

12,113

12,113 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

12,113 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).

8,174 in the last 10 years · low confidence

Phrase hits: 252 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,238

Distinct author names in 200 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
    Kinoshita T6 papers · 2022

    WPI Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan tkinoshi@biken.osaka-u.ac.jp.

    Papers in Europe PMC
  2. 02
    Kamnasaran D5 papers · 2013

    Department of Pediatrics, Laval University, Centre de recherche de CHUL, 1705 Boulevard Laurier, Québec, Québec, Canada. deepak.kamnasaran@crchul.ulaval.ca

    Papers in Europe PMC
  3. 03
    Chen CP4 papers · 2021

    Department of Materials Engineering, Ming Chi University of Technology, New Taipei City, Taiwan.

    Papers in Europe PMC
  4. 04
    Maeda Y4 papers · 2022

    Research Institute for Microbial Diseases and WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.

    Papers in Europe PMC
  5. 05
    Miller KA4 papers · 2024

    Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

    Papers in Europe PMC
  6. 06
    Sergi C4 papers · 2021

    Department of Lab. Med. & Pathology (5B4.09), University of Alberta, Edmonton, AB, Canada.

    Papers in Europe PMC
  7. 07
    Zhang Y4 papers · 2025

    Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    Papers in Europe PMC
  8. 08
    Aizawa S3 papers · 2002
    Papers in Europe PMC
  9. 09
    Chassaing N3 papers · 2021

    Department of Medical Genetics, Purpan Hospital, CHU Toulouse, Toulouse, France. chassaing.n@chu-toulouse.fr

    Papers in Europe PMC
  10. 10
    Fujita M3 papers · 2020

    Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, 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 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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-29

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 Agnathia-holoprosencephaly-situs inversus 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.

("Agnathia-holoprosencephaly-situs inversus syndrome" OR "agnathia-otocephaly complex" OR "dysgnathia complex agnathia-holoprosencephaly" OR "holoprosencephaly-agnathia" OR "otocephaly") OR ("OTX2" OR "OTX2 syndrome" OR "OTX2-related" OR "PRRX1" OR "PRRX1 syndrome" OR "PRRX1-related")

Run this search on Europe PMC

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

"Agnathia-holoprosencephaly-situs inversus syndrome" OR "agnathia-otocephaly complex" OR "dysgnathia complex agnathia-holoprosencephaly" OR "holoprosencephaly-agnathia" OR "otocephaly"

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

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 (12113) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T16:08:05.298Z