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ORPHA:638

Neurofibromatosis-Noonan syndrome

medium confidenceDisorder

Also known as: NFNS · Neurofibromatosis type 1-Noonan syndrome

Publications

259

61.3th percentile

Trials

0

Interventional, condition-specific

Researchers

1,317

Distinct authors in sample

Gene link

NF1

Strong

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS).

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (2)

neurofibromatosis type 1-Noonan syndrome · neurofibromatosis-Noonan 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

    Strong — NF1

  2. LiteraturePresent

    259 matched papers (133 in last 10 years) Source

  3. Phenotype characterisedPresent

    69 HPO annotations (e.g. Webbed neck; Downslanted palpebral fissures; Ptosis) 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; 165 for broader category neurofibromatosis

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 (NF1).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

69

Associated phenotypes · MONDO:0011035

  • Webbed neck
  • Downslanted palpebral fissures
  • Ptosis
  • Specific learning disability
  • Hypertrophic cardiomyopathy

Showing 5 of 69 — 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?

259

259 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=3967) is 59.

259 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).

133 in the last 10 years · medium confidence · 61.3th percentile (publications denominator)

Phrase hits: 259 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,317

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
    Tartaglia M10 papers · 2022

    Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy. Electronic address: marco.tartaglia@opbg.net.

    Papers in Europe PMC
  2. 02
    Zenker M10 papers · 2026

    Institute of Human Genetics, University Hospital Magdeburg, 39120 Magdeburg, Germany.

    Papers in Europe PMC
  3. 03
    Gelb BD8 papers · 2021

    Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

    Papers in Europe PMC
  4. 04
    Dallapiccola B7 papers · 2021

    Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.

    Papers in Europe PMC
  5. 05
    De Luca A6 papers · 2022

    Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

    Papers in Europe PMC
  6. 06
    Digilio MC6 papers · 2019

    Division of Medical Genetics, Bambino Gesù Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

    Papers in Europe PMC
  7. 07
    Zampino G6 papers · 2015

    Istituto di Clinica Pediatrica, Università Cattolica del Sacro Cuore, Rome, Italy.

    Papers in Europe PMC
  8. 08
    Vidaud D5 papers · 2025

    Service de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.

    Papers in Europe PMC
  9. 09
    Rauen KA4 papers · 2023

    MIND Institute, University of California at Davis, Sacramento, California.

    Papers in Europe PMC
  10. 10
    Sarkozy A4 papers · 2008

    IRCCS-CSS, San Giovanni Rotondo and CSS-Mendel Institute, Viale Regina Elena 261, 00198, Rome, Italy. a.sarkozy@css-mendel.it

    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. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial. 165 trials are registered for neurofibromatosis, 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.

medium 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.

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

Broader category: neurofibromatosis

165

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

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.

Recruiting or not-yet-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 2026-07-29

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 Neurofibromatosis-Noonan 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.

"Neurofibromatosis-Noonan syndrome" OR "Neurofibromatosis type 1-Noonan syndrome"

Run this search on Europe PMC

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

"Neurofibromatosis-Noonan syndrome" OR "Neurofibromatosis type 1-Noonan syndrome"

Study-type breakdown: 0 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"neurofibromatosis"

Query health: ok — strategies attempted: phrase; with hits: phrase

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: NFNS

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

Ingested 2026-07-26T14:39:45.296Z