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ORPHA:101088

X-linked hyper-IgM syndrome

low confidenceSubtype of disorder

Also known as: HIGM1 · Hyper-IgM syndrome due to CD40 ligand deficiency · Hyper-IgM syndrome due to CD40L deficiency · Hyper-IgM syndrome type 1 · XHIGM

Publications

5,265

Trials

3

Interventional, condition-specific

Researchers

1,322

Distinct authors in sample

Gene link

CD40LG

Definitive

Readiness

5/6

Stages with a signal

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (7)

Hyper IgM Syndromes · hyper-IgM syndrome due to CD40 ligand deficiency · hyper-IgM syndrome due to CD40L deficiency · hyper-IgM syndrome type 1 · hyper-IgM syndrome, X-linked · hyperimmunoglobulin M syndrome · immunodeficiency, X-linked, with hyper-IgM, X-linked recessive

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 — CD40LG

  2. LiteraturePresent

    5,265 matched papers (4,067 in last 10 years) Source

  3. Phenotype characterisedPresent

    53 HPO annotations (e.g. Global developmental delay; Decreased T cell activation; Decreased circulating IgE concentration) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationPartial

    1 EMA designation (none yet with FDA orphan-indication approval) — e.g. autologous peripheral blood-derived CD4 T-cells CRISPR-edited at the CD40LG locus Source

  6. 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 (CD40LG).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

53

Associated phenotypes · MONDO:0010626

  • Global developmental delay
  • Decreased T cell activation
  • Decreased circulating IgE concentration
  • Highly elevated creatine kinase
  • Myalgia

Showing 5 of 53 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

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)

1

Designation · no FDA orphan-indication approval yet

  • EMA autologous peripheral blood-derived CD4 T-cells CRISPR-edited at the CD40LG locusTreatment of hyper IgM syndromes · 16/05/2022 · PositiveEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

3

Drugs / clinical candidates · MONDO_0010626

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

5,265

5,265 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.

5,265 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).

4,067 in the last 10 years · low confidence

Phrase hits: 1,017 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,322

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
    Lu G8 papers · 2025

    Department of Respiratory Infection, Guangzhou Medical University, No.9, Jinsui Road, Zhujiang New City, Tianhe District, Guangzhou, 510120, Guangdong, China.

    Papers in Europe PMC
  2. 02
    Wang Y6 papers · 2026

    Department of Pulmonology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

    Papers in Europe PMC
  3. 03
    de la Morena MT5 papers · 2019

    Department of Pediatrics/Immunology, University of Washington and Seattle Children's Research Institute, Seattle, Wash.

    Papers in Europe PMC
  4. 04
    Fan H5 papers · 2025

    Department of Respiratory Infection, Guangzhou Medical University, No.9, Jinsui Road, Zhujiang New City, Tianhe District, Guangzhou, 510120, Guangdong, China. sonny-000@163.com.

    Papers in Europe PMC
  5. 05
    Huang L5 papers · 2025

    Pediatric Intensive Care Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No.9, Jinsui Road, Zhujiang New City, Tianhe District, Guangzhou, 510120, Guangdong, China. huangli7525@163.com.

    Papers in Europe PMC
  6. 06
    Li L5 papers · 2026

    Chinese Organization for Rare Disorders, Beijing, China.

    Papers in Europe PMC
  7. 07
    Li Y5 papers · 2026

    Department of Gastroenterology and Respiratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.

    Papers in Europe PMC
  8. 08
    Ochs HD5 papers · 2025

    c Department of Pediatrics , University of Washington School of Medicine, and Seattle Children's Research Institute , Seattle , WA , USA.

    Papers in Europe PMC
  9. 09
    Chen Y4 papers · 2026

    Chinese Organization for Rare Disorders, Beijing, China.

    Papers in Europe PMC
  10. 10
    Cunningham-Rundles C4 papers · 2023

    Departments of Medicine and Pediatrics, The Prism Immunology Institute, The Icahn School of Medicine at Mount Sinai; New York, USA

    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. 3 trials are registered for hyper-IgM syndrome, the broader category — shown separately because they may or may not enrol this specific subtype.

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

3 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 86.7th percentile).

low confidence · 86.7th 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: hyper-IgM syndrome

3

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.

None of the matched observational studies is currently listed as 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 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 X-linked hyper-IgM 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.

("X-linked hyper-IgM syndrome" OR "HIGM1" OR "Hyper-IgM syndrome due to CD40 ligand deficiency" OR "Hyper-IgM syndrome due to CD40L deficiency" OR "Hyper-IgM syndrome type 1" OR "XHIGM" OR "Hyper IgM Syndromes" OR "hyper-IgM syndrome, X-linked" OR "hyperimmunoglobulin M syndrome" OR "immunodeficiency, X-linked, with hyper-IgM, X-linked recessive") OR ("CD40LG" OR "CD40LG syndrome" OR "CD40LG-related")

Run this search on Europe PMC

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

"X-linked hyper-IgM syndrome" OR "HIGM1" OR "Hyper-IgM syndrome due to CD40 ligand deficiency" OR "Hyper-IgM syndrome due to CD40L deficiency" OR "Hyper-IgM syndrome type 1" OR "XHIGM" OR "Hyper IgM Syndromes" OR "hyper-IgM syndrome, X-linked" OR "hyperimmunoglobulin M syndrome" OR "immunodeficiency, X-linked, with hyper-IgM, X-linked recessive"

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: 3 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"hyper-IgM syndrome"

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

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
  • Publication count (5265) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-27T07:18:06.888Z