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ORPHA:420741

RIDDLE syndrome

low confidenceDisorder

Also known as: RNF168 deficiency · Radiosensitivity-immunodeficiency-dysmorphic features-learning difficulties syndrome

Publications

19,676

Trials

0

Interventional, condition-specific

Researchers

1,024

Distinct authors in sample

Gene link

RNF168

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic, primary immunodeficiency disorder characterized by increased radiosensitivity(R), mild immunodeficiency (ID), features (D), and learning difficulties (LE).

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)

radiosensitivity-immunodeficiency-dysmorphic features-learning difficulties 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 matched interventional trial, but a gene association and an animal model are on record — often described as translation-ready / stalled at the clinical step.

  1. Gene identifiedPresent

    Definitive — RNF168

  2. LiteraturePresent

    19,676 matched papers (8,368 in last 10 years) Source

  3. Phenotype characterisedPresent

    53 HPO annotations (e.g. Elevated circulating alpha-fetoprotein concentration; Chromosomal breakage induced by ionizing radiation; Specific learning disability) 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 trialNot found

    No matched interventional trial under our ClinicalTrials.gov rules

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 (RNF168).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

53

Associated phenotypes · MONDO:0012764

  • Elevated circulating alpha-fetoprotein concentration
  • Chromosomal breakage induced by ionizing radiation
  • Specific learning disability
  • Recurrent fever
  • Abnormal facial shape

Showing 5 of 53 — 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?

19,676

19,676 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.

19,676 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).

8,368 in the last 10 years · low confidence

Phrase hits: 166 · MeSH hits: 3

Open Europe PMC search

Who's working on it?

1,024

Distinct author names in 166 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
    Stewart GS13 papers · 2025

    Cancer Research UK, Institute for Cancer Studies, Birmingham University, Vincent Drive, Edgbaston, Birmingham, United Kingdom. g.s.stewart@bham.ac.uk

    Papers in Europe PMC
  2. 02
    Chen J9 papers · 2022

    Genome Stability Research Laboratory, The University of Hong Kong, Hong Kong, China.

    Papers in Europe PMC
  3. 03
    Casanova JL7 papers · 2020

    St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY , USA ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Imagine Institut, Necker Medical School, University Paris Descartes , Paris , France.

    Papers in Europe PMC
  4. 04
    Durocher D7 papers · 2019

    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

    Papers in Europe PMC
  5. 05
    Cunningham-Rundles C6 papers · 2025

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

    Papers in Europe PMC
  6. 06
    Franco JL6 papers · 2020

    Group of Primary Immunodeficiencies, University of Antioquia , Medellin , Colombia.

    Papers in Europe PMC
  7. 07
    Hakem R6 papers · 2021

    Ontario Cancer Institute, University Health Network and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, M5G 2M9 Ontario, Canada.

    Papers in Europe PMC
  8. 08
    Huen MS6 papers · 2017

    Department of Anatomy, Centre for Cancer Research, University of Hong Kong, L1-59, Laboratory Block, 21 Sassoon Road, Hong Kong SAR.

    Papers in Europe PMC
  9. 09
    Picard C6 papers · 2025

    Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Imagine Institut, Necker Medical School, University Paris Descartes , Paris , France ; Centre d'Étude des Déficits Immunitaires (CEDI), Hôpital Necker-Enfants Malades, AP-HP , Paris , France.

    Papers in Europe PMC
  10. 10
    Al-Herz W5 papers · 2020

    Department of Pediatrics, Kuwait University , Kuwait City , Kuwait ; Allergy and Clinical Immunology Unit, Department of Pediatrics, Al-Sabah Hospital , Kuwait City , Kuwait.

    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 on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).

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.

low 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.

See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.

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 1 · after dedupe 1 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 1 · dropped 0 · fetched 2026-07-30

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 (1)

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 RIDDLE 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.

("RIDDLE syndrome" OR "RNF168 deficiency" OR "Radiosensitivity-immunodeficiency-dysmorphic features-learning difficulties syndrome") OR (MESH:"Riddle Syndrome") OR ("RNF168" OR "RNF168 syndrome" OR "RNF168-related" OR "RIDDLE" OR "RIDDLE-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Riddle Syndrome

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

"RIDDLE syndrome" OR "RNF168 deficiency" OR "Radiosensitivity-immunodeficiency-dysmorphic features-learning difficulties syndrome"

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

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

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 (19676) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T15:49:56.800Z