ORPHA:576349
NLRC4-related familial cold autoinflammatory syndrome
Also known as: FCAS4 · Familial cold autoinflammatory syndrome 4 · NLRC4-related familial cold urticaria
Publications
53
53th percentile
Trials
3
Interventional, condition-specific
Researchers
333
Distinct authors in sample
Gene link
NLRC4
Strong
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare periodic fever syndrome characterized by or childhood onset of episodes of fever and cold-induced urticaria-like rash and arthralgias. Ocular features such as conjunctivitis and uveitis may also be present. Presentation is typically mild, and symptoms resolve without treatment in most cases.
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0014498
- OMIM:616115
- UMLS:C4015276
Additional Mondo synonyms (4)
NLRC4 familial cold autoinflammatory syndrome · familial cold autoinflammatory syndrome 4 · familial cold autoinflammatory syndrome caused by mutation in NLRC4 · familial cold autoinflammatory syndrome type 4
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
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Strong — NLRC4
- LiteraturePresent
53 matched papers (49 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- Interventional trialPresent
3 matched on ClinicalTrials.gov
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 (NLRC4).
GenCC classification: Strong.
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?
53
53 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.
53 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).
49 in the last 10 years · high confidence · 53th percentile (publications denominator)
Phrase hits: 53 · MeSH hits: 0
Who's working on it?
333
Distinct author names in 53 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.
- 01Sullivan KE5 papers · 2025
Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Papers in Europe PMC - 02Cunningham-Rundles C4 papers · 2025
Department of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY, USA.
Papers in Europe PMC - 03Klein C4 papers · 2025
Dr von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
Papers in Europe PMC - 04Picard C4 papers · 2025
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Hospital for Sick Children, Paris, France.
Papers in Europe PMC - 05Al-Herz W3 papers · 2020
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Papers in Europe PMC - 06Bousfiha A3 papers · 2020
Clinical Immunology Unit, Casablanca Children's Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco.
Papers in Europe PMC - 07Casanova JL3 papers · 2020
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Hospital for Sick Children, Paris, France.
Papers in Europe PMC - 08Chatila T3 papers · 2020
Division of Immunology, Children's Hospital Boston, Boston, MA, USA.
Papers in Europe PMC - 09
- 10Franco JL3 papers · 2020
Group of Primary Immunodeficiencies, University of Antioquia, Medellin, Colombia.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
3
interventional trials for this specific condition
3 interventional trials matched this specific condition name; none in our sample are currently recruiting. 7 trials are registered for familial cold autoinflammatory syndrome, the broader category — shown separately because they may or may not enrol this specific subtype.
Data as of 27 July 2026
3 interventional trials — more than 73% of diseases in the trials denominator have none at all (5114 of 7003; this disease is at the 85.1th percentile).
high confidence · 85.1th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
3 interventional trials matched after quoted-phrase search and title/condition post-filter.
No currently recruiting studies in the matched set. Open the same search on ClinicalTrials.gov.
Broader category: familial cold autoinflammatory syndrome
7
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.
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
- NCT02974595·RECRUITING·Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
Conditions: NOMID · DIRA · NLRC4-MAS · SAVI·Matched via recall expansion
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 2026-07-26This 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.
"NLRC4-related familial cold autoinflammatory syndrome" OR "FCAS4" OR "Familial cold autoinflammatory syndrome 4" OR "NLRC4-related familial cold urticaria" OR "NLRC4 familial cold autoinflammatory syndrome" OR "familial cold autoinflammatory syndrome caused by mutation in NLRC4" OR "familial cold autoinflammatory syndrome type 4"
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"NLRC4-related familial cold autoinflammatory syndrome" OR "FCAS4" OR "Familial cold autoinflammatory syndrome 4" OR "NLRC4-related familial cold urticaria" OR "NLRC4 familial cold autoinflammatory syndrome" OR "familial cold autoinflammatory syndrome caused by mutation in NLRC4" OR "familial cold autoinflammatory syndrome type 4" OR "NLRC4"
Recall-expansion terms: NLRC4
Interventional trials matched via: recall-expansion (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 3 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.
Parent-category trials query:
"familial cold autoinflammatory syndrome"
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
- No label/synonym collisions with other diseases in this corpus
Ingested 2026-07-27T18:38:36.271Z