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ORPHA:2268

ICF syndrome

low confidenceDisorder

Also known as: Immunodeficiency-centromeric instability-facial anomalies syndrome · Immunodeficiency-centromeric instability-facial dysmorphism syndrome

Publications

5,943

Trials

0

Interventional, condition-specific

Researchers

1,471

Distinct authors in sample

Gene link

UHRF1

Limited

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare syndrome with combined immunodeficiency characterized by the clinical triad of immunodeficiency, centromeric instability and facial anomalies (abbreviated ICF syndrome). The immunodeficiency is with panhypogammaglobulinemia, and a lack of memory (CD19+CD27+) B cells in the peripheral blood, although B and T-cell counts are normal. Anomalies and rearrangements associated with DNA hypomethylation in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9, in mitogen-stimulated lymphocytes, is a hallmark of the syndrome. The typical facial anomalies include hypertelorism, low-set ears, epicanthus and macroglossia.

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)

immunodeficiency-centromeric instability-facial anomalies · immunodeficiency-centromeric instability-facial anomalies 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

    Limited — UHRF1

  2. LiteraturePresent

    5,943 matched papers (4,268 in last 10 years) Source

  3. Phenotype characterisedPresent

    107 HPO annotations (e.g. Global developmental delay; Agammaglobulinemia; Intellectual disability) Source

  4. Animal modelPresent

    8 genotype models (Danio rerio, 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?

Possibly — only limited evidence so far for UHRF1.

GenCC classification: Limited.

Phenotypes (Monarch / HPO)

107

Associated phenotypes · MONDO:0000133

  • Global developmental delay
  • Agammaglobulinemia
  • Intellectual disability
  • Strabismus
  • Short nose

Showing 5 of 107 — open Monarch for the full list.

Animal models (Monarch / Alliance)

8

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?

5,943

5,943 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.

5,943 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).

4,268 in the last 10 years · low confidence

Phrase hits: 929 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,471

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
    Sadikovic B20 papers · 2025

    Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada. Bekim.Sadikovic@lhsc.on.ca.

    Papers in Europe PMC
  2. 02
    Kerkhof J15 papers · 2024

    Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.

    Papers in Europe PMC
  3. 03
    Levy MA13 papers · 2025

    Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.

    Papers in Europe PMC
  4. 04
    McConkey H12 papers · 2025

    Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, Canada.

    Papers in Europe PMC
  5. 05
    Stevenson RE9 papers · 2023

    Greenwood Genetic Center, Greenwood, SC, USA.

    Papers in Europe PMC
  6. 06
    Unoki M9 papers · 2026

    Division of Epigenomics and Development, Medical Institute of Bioregulation, University of Tokyo, Fukuoka 812-8582, Japan.

    Papers in Europe PMC
  7. 07
    Chen T8 papers · 2026

    Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

    Papers in Europe PMC
  8. 08
    Haghshenas S8 papers · 2024

    Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.

    Papers in Europe PMC
  9. 09
    Liu B8 papers · 2026

    Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

    Papers in Europe PMC
  10. 10
    Relator R8 papers · 2025

    Verspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.

    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 40 · after dedupe 39 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 39 · 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 (39)

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 ICF 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.

("ICF syndrome" OR "Immunodeficiency-centromeric instability-facial anomalies syndrome" OR "Immunodeficiency-centromeric instability-facial dysmorphism syndrome" OR "immunodeficiency-centromeric instability-facial anomalies") OR ("UHRF1" OR "UHRF1 syndrome" OR "UHRF1-related" OR "ICF-related")

Run this search on Europe PMC

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

"ICF syndrome" OR "Immunodeficiency-centromeric instability-facial anomalies syndrome" OR "Immunodeficiency-centromeric instability-facial dysmorphism syndrome" OR "immunodeficiency-centromeric instability-facial anomalies"

Study-type breakdown: 0 interventional · 0 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 (5943) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T19:38:12.478Z