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ORPHA:500

Noonan syndrome with multiple lentigines

low confidenceDisorder

Also known as: Cardiomyopathic lentiginosis · Familial multiple lentigines syndrome · LEOPARD syndrome

Query health: suspect — Source fetch failed for trials.

Publications

43,066

Trials

—

Interventional, condition-specific

Researchers

1,206

Distinct authors in sample

Gene link

BRAF, MAP2K1, NRAS

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare multisystem genetic disorder characterized by cutaneous lentigines, hypertrophic , short stature, pectus deformity, and facial features.

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 (3)

familial multiple lentigines syndrome · generalised lentiginosis · lentigines, electrocardiographic conduction defects, 0cular hypertelorism, pulmonary stenosis, abnormalities of the genitals, retarded Growth, deafness

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

Research-stage checklist from open sources (GenCC, literature, Monarch when enriched, ClinicalTrials.gov). Not a prognosis or care recommendation.

  1. Gene identifiedPresent

    Definitive — BRAF, MAP2K1, NRAS, PTPN11, RAF1

  2. LiteraturePresent

    43,066 matched papers (25,537 in last 10 years) Source

  3. Phenotype characterisedPresent

    145 HPO annotations (e.g. Sensorineural hearing impairment; Hyperextensible skin; Melanocytic nevus) Source

  4. Animal modelPresent

    4 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 checked

    Trial fetch failed or incomplete

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 (BRAF, MAP2K1, NRAS…).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

145

Associated phenotypes · MONDO:0007893

  • Sensorineural hearing impairment
  • Hyperextensible skin
  • Melanocytic nevus
  • Freckling
  • Growth delay

Showing 5 of 145 — open Monarch for the full list.

Animal models (Monarch / Alliance)

4

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)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

43,066

43,066 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.

43,066 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).

25,537 in the last 10 years · low confidence

Phrase hits: 1,946 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,206

Distinct author names in 200 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
    Tartaglia M14 papers · 2026

    Genetics and Rare Disease Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

    Papers in Europe PMC
  2. 02
    Gelb BD8 papers · 2026

    Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

    Papers in Europe PMC
  3. 03
    Limongelli G8 papers · 2026

    Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples; Division of Cardiology, A.O.R.N. "Sant'Anna & San Sebastiano", Caserta I-81100, Italy. Electronic address: limongelligiuseppe@libero.it.

    Papers in Europe PMC
  4. 04
    Monda E7 papers · 2026

    Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples.

    Papers in Europe PMC
  5. 05
    Calcagni G5 papers · 2024

    The European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart - ERN GUARD-Heart; Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children's Hospital IRCSS, Rome, Italy.

    Papers in Europe PMC
  6. 06
    Kaski JP5 papers · 2026

    Centre for Pediatric Inherited and Rare Cardiovascular Disease, University College London Institute of Cardiovascular Science, London, UK.

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

    Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.

    Papers in Europe PMC
  8. 08
    Caiazza M4 papers · 2023

    Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

    Papers in Europe PMC
  9. 09
    Lioncino M4 papers · 2023

    Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples.

    Papers in Europe PMC
  10. 10
    Mussa A4 papers · 2026

    Department of Public Health and Pediatric Sciences, University of Torino, 10126 Turin, Italy.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

—

interventional trials for this specific condition

We could not load trial data for this condition right now.

Data as of 11 September 2026 · last trial check 31 July 2026

low confidence

Recruiting interventional trials

From the matched ClinicalTrials.gov set

Trial data could not be loaded for this build. This is not the same as finding zero interventional trials.

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 Noonan syndrome with multiple lentigines — 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.

("Noonan syndrome with multiple lentigines" OR "Cardiomyopathic lentiginosis" OR "Familial multiple lentigines syndrome" OR "LEOPARD syndrome" OR "generalised lentiginosis" OR "lentigines, electrocardiographic conduction defects, 0cular hypertelorism, pulmonary stenosis, abnormalities of the genitals, retarded Growth, deafness" OR "lentigines, electrocardiographic conduction defects, 0cular hypertelorism, pulmonary stenosis, abnormalities of genitals, retarded Growth, deafness") OR ("MAP2K1" OR "MAP2K1 syndrome" OR "MAP2K1-related" OR "PTPN11" OR "PTPN11 syndrome" OR "PTPN11-related" OR "RAF1" OR "RAF1 syndrome" OR "RAF1-related")

Run this search on Europe PMC

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

"Noonan syndrome with multiple lentigines"

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

Run this search on ClinicalTrials.gov

Source errors: trials: Error: HTTP 400 for https://clinicaltrials.gov/api/v2/studies?query.cond=%22Noonan%20syndrome%20with%20multiple%20lentigines%22%20OR%20%22Cardiomyopathic%20lentiginosis%22%20OR%20%22Familial%20multiple%20lentigines%20syndrome%22%20OR%20%22LEOPARD%20syndrome%22%20OR%20%22generalised%20lentiginosis%22%20OR%20%22lentigines%2C%20electrocardiographic%20conduction%20defects%2C%200cular%20hypertelorism%2C%20pulmonary%20stenosis%2C%20abnormalities%20of%20the%20genitals%2C%20retarded%20Growth%2C%20deafness%22%20OR%20%22lentigines%2C%20electrocardiographic%20conduction%20defects%2C%200cular%20hypertelorism%2C%20pulmonary%20stenosis%2C%20abnormalities%20of%20genitals%2C%20retarded%20Growth%2C%20deafness%22&format=json&pageSize=100&countTotal=true

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 (43066) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T14:03:28.561Z