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ORPHA:3071

Costello syndrome

low confidenceDisorder

Also known as: FCS syndrome · Faciocutaneoskeletal syndrome

Publications

43,194

Trials

5

Interventional, condition-specific

Researchers

1,233

Distinct authors in sample

Gene link

BRAF, HRAS, KRAS

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A rare syndrome with , characterized by , short stature, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors. Costello syndrome belongs to the RASopathies, a group of conditions resulting from germline derived point mutations affecting the RAS-mitogen activated protein kinase pathway.

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 (2)

congenital myopathy with excess of muscle spindles · faciocutaneoskeletal 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.”

5/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — BRAF, HRAS, KRAS, MAP2K1, NRAS…

  2. LiteraturePresent

    43,194 matched papers (25,650 in last 10 years) Source

  3. Phenotype characterisedPresent

    127 HPO annotations (e.g. Narrow palate; Short neck; Concave nail) 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 trialPresent

    5 matched on ClinicalTrials.gov (2 recruiting in sample)

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, HRAS, KRAS…).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

127

Associated phenotypes · MONDO:0009026

  • Narrow palate
  • Short neck
  • Concave nail
  • Ventricular septal defect
  • Deep-set nails

Showing 5 of 127 — 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)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

43,194

43,194 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.

43,194 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).

25,650 in the last 10 years · low confidence

Phrase hits: 1,856 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,233

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
    Leoni C14 papers · 2026

    Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

    Papers in Europe PMC
  2. 02
    Zampino G12 papers · 2026

    Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

    Papers in Europe PMC
  3. 03
    Onesimo R10 papers · 2025

    Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

    Papers in Europe PMC
  4. 04
    Viscogliosi G8 papers · 2026

    Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

    Papers in Europe PMC
  5. 05
    Stewart DR7 papers · 2026

    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.

    Papers in Europe PMC
  6. 06
    Tartaglia M7 papers · 2026

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

    Papers in Europe PMC
  7. 07
    Chennappan S6 papers · 2025

    Masonic Medical Research Institute, Department of Biological Sciences and Translational Medicine, Utica, New York, USA.

    Papers in Europe PMC
  8. 08
    Flex E6 papers · 2026

    Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy.

    Papers in Europe PMC
  9. 09
    Gripp KW6 papers · 2024

    Division of Medical Genetics, Nemours Children's Hospital, Wilmington, Delaware, USA.

    Papers in Europe PMC
  10. 10
    Cirstea IC5 papers · 2025

    Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany. ion.cirstea@uni-ulm.de.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

5

interventional trials for this specific condition

5 interventional trials matched this specific condition name; 2 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

5 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 89.2th percentile).

low confidence · 89.2th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

5 interventional trials matched after quoted-phrase search and title/condition post-filter.

Observational and natural-history studies

3 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

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 2 · after dedupe 2 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 2 · 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).

Uncertain / not reviewed (2)

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 Costello 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.

("Costello syndrome" OR "FCS syndrome" OR "Faciocutaneoskeletal syndrome" OR "congenital myopathy with excess of muscle spindles" OR "congenital myopathy with excess of the muscle spindles") 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):

"Costello syndrome" OR "FCS syndrome" OR "Faciocutaneoskeletal syndrome" OR "congenital myopathy with excess of muscle spindles" OR "congenital myopathy with excess of the muscle spindles"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 5 interventional · 3 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 short or not clearly distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (43194) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T22:08:42.574Z