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ORPHA:453499

Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome

low confidenceDisorder

Also known as: Au-Kline syndrome · HNRNPK-related neurodevelopmental disorder · Okamoto syndrome

Publications

3,731

Trials

0

Interventional, condition-specific

Researchers

772

Distinct authors in sample

Gene link

HNRNPK

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare genetic multiple anomalies/ syndrome characterized by global , , , craniofacial dysmorphism (such as ridged metopic sutures, long palpebral fissures, broad nasal bridge, hypoplastic alae nasi, low-set, prominent ears, prominent midline tongue groove, and downturned mouth), heart defects, and variable skeletal abnormalities including hip , vertebral anomalies, and scoliosis. Additional reported manifestations include high pain tolerance and genitourinary anomalies. Brain imaging may show a thin corpus callosum or white matter abnormalities.

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)

neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia 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 — HNRNPK

  2. LiteraturePresent

    3,731 matched papers (2,983 in last 10 years) Source

  3. Phenotype characterisedPresent

    320 HPO annotations (e.g. Long palpebral fissure; Hypotonia; Cryptorchidism) 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; 40 for broader category neurodevelopmental disorder

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 (HNRNPK).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

320

Associated phenotypes · MONDO:0018681

  • Long palpebral fissure
  • Hypotonia
  • Cryptorchidism
  • Wide nasal bridge
  • Broad nasal tip

Showing 5 of 320 — 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?

3,731

3,731 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.

3,731 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).

2,983 in the last 10 years · low confidence

Phrase hits: 88 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

772

Distinct author names in 88 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
    Weksberg R6 papers · 2025

    Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

    Papers in Europe PMC
  2. 02
    Choufani S5 papers · 2025

    Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

    Papers in Europe PMC
  3. 03
    Stewart H5 papers · 2025

    Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

    Papers in Europe PMC
  4. 04
    Au PYB4 papers · 2025

    Department of Medical Genetics, University of Calgary, Cumming School of Medicine, Calgary, AB, Canada. billie.au@ahs.ca.

    Papers in Europe PMC
  5. 05
    Cheng X4 papers · 2026

    College of Life Science, Xinyang Normal University, Xinyang 464000, China.

    Papers in Europe PMC
  6. 06
    Faivre L4 papers · 2025

    Institut National de la Santé et de la Recherche Médicale UMR 1231 GAD, Génétique des Anomalies du Dévelopement, Université de Bourgogne-Franche Comté, F-21079 Dijon, France.

    Papers in Europe PMC
  7. 07
    Innes AM4 papers · 2025

    Department of Medical Genetics, University of Calgary, Cumming School of Medicine, Calgary, AB, Canada.

    Papers in Europe PMC
  8. 08
    Kline AD4 papers · 2025

    Harvey Institute for Human Genetics, Department of Pediatrics, Greater Baltimore Medical Center, Baltimore, MD, USA.

    Papers in Europe PMC
  9. 09
    Li C4 papers · 2026

    College of Life Science, Xinyang Normal University, Xinyang 464000, China.

    Papers in Europe PMC
  10. 10
    Wang Y4 papers · 2025

    College of Life Science, Xinyang Normal University, Xinyang 464000, 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). 40 trials are registered for neurodevelopmental disorder, 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.

40 interventional trials matched neurodevelopmental disorder, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: neurodevelopmental disorder

40

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 Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies 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.

("Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome" OR "Au-Kline syndrome" OR "HNRNPK-related neurodevelopmental disorder" OR "Okamoto syndrome" OR "neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome") OR ("HNRNPK" OR "HNRNPK syndrome" OR "HNRNPK-related")

Run this search on Europe PMC

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

"Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome" OR "Au-Kline syndrome" OR "HNRNPK-related neurodevelopmental disorder" OR "Okamoto syndrome" OR "neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome"

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

Parent-category trials query:

"neurodevelopmental disorder"

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
  • "Okamoto syndrome" also appears on ORPHA:2729
  • Publication count (3731) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T16:40:49.500Z