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ORPHA:453499

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

medium confidenceDisorder

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

Publications

88

63.1th percentile

Trials

0

Interventional, condition-specific

Researchers

772

Distinct authors in sample

Gene link

HNRNPK

Definitive

Readiness

3/6

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.”

3/6 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

    88 matched papers (82 in last 10 years) Source

  3. Phenotype characterisedNot checked

    Not yet enriched from Monarch / HPO

  4. Animal modelNot checked

    Not yet enriched from Monarch / Alliance

  5. Orphan designationNot checked

    FDA/EMA orphan-drug designation not enriched yet

  6. Interventional trialPartial

    None under the specific name; 39 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)

Not enriched in this build — Monarch phenotype joins were not run for this record.

Animal models (Monarch / Alliance)

Not enriched in this build.

Literature

Is anyone studying this?

88

88 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=5449) is 41.

88 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).

82 in the last 10 years · medium confidence · 63.1th percentile (publications denominator)

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. 2 observational studies did — shown below because natural-history and cohort work can be an important step toward a trial. 39 trials are registered for neurodevelopmental disorder, the broader category — shown separately because they may or may not enrol this specific subtype.

Data as of 27 July 2026

No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.

medium confidence · 36.5th 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.

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

Broader category: neurodevelopmental disorder

39

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

Observational and natural-history studies

2 observational studies match 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.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

Where to find support

We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:

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"

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" OR "HNRNPK"

Recall-expansion terms: HNRNPK

Study-type breakdown: 0 interventional · 2 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"neurodevelopmental disorder"

Query health: ok — strategies attempted: phrase, recall-expansion; with hits: phrase, recall-expansion

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

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