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ORPHA:99812

LIG4 syndrome

low confidenceDisorder

Also known as: DNA ligase IV syndrome · SCID with macrocephaly due to DNA ligase IV deficiency

Publications

4,013

Trials

0

Interventional, condition-specific

Researchers

1,378

Distinct authors in sample

Gene link

LIG4

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

LIG4 syndrome is a disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and , skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).

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)

DNA ligase IV deficiency · ligase 4 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 — LIG4

  2. LiteraturePresent

    4,013 matched papers (2,541 in last 10 years) Source

  3. Phenotype characterisedPresent

    68 HPO annotations (e.g. Cryptorchidism; Astigmatism; Upslanted palpebral fissure) 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 (LIG4).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

68

Associated phenotypes · MONDO:0011686

  • Cryptorchidism
  • Astigmatism
  • Upslanted palpebral fissure
  • Telangiectasia
  • Psoriasiform dermatitis

Showing 5 of 68 — 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?

4,013

4,013 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

4,013 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).

2,541 in the last 10 years · low confidence

Phrase hits: 340 · MeSH hits: 3

Open Europe PMC search

Who's working on it?

1,378

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
    Jeggo PA12 papers · 2016

    Genome Damage and Stability Centre, University of Sussex, East Sussex BN19RQ, UK p.a.jeggo@sussex.ac.uk.

    Papers in Europe PMC
  2. 02
    de Villartay JP6 papers · 2026

    Université de Paris, Imagine Institute, Laboratory "Genome Dynamics in the Immune System", INSERM UMR 1163, F-75015, Paris, France.

    Papers in Europe PMC
  3. 03
    Gennery AR6 papers · 2022

    Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

    Papers in Europe PMC
  4. 04
    O'Driscoll M5 papers · 2024

    Human DNA Damage Response Disorders Group Genome Damage and Stability Centre, University of Sussex, Brighton, East Sussex BN1 9RQ, United Kingdom.

    Papers in Europe PMC
  5. 05
    Woodbine L5 papers · 2014

    Genome Damage and Stability Centre, University of Sussex, Brighton, BN1 9RQ, UK.

    Papers in Europe PMC
  6. 06
    Al-Choboq J4 papers · 2025

    Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre Léon-Bérard, 69008 Lyon, France.

    Papers in Europe PMC
  7. 07
    Blundell TL4 papers · 2014

    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.

    Papers in Europe PMC
  8. 08
    Bourguignon M4 papers · 2025

    Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre Léon-Bérard, 69008 Lyon, France.

    Papers in Europe PMC
  9. 09
    Foray N4 papers · 2025

    Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre Léon-Bérard, 69008 Lyon, France.

    Papers in Europe PMC
  10. 10
    Imai K4 papers · 2025

    Department of Community Pediatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

    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. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial.

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.

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

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

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 LIG4 syndrome — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Severe combined immunodeficiency (SCID) as a category (Group 1), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 1 — one-time curative treatment

Up to ₹50 lakh per patient

Financial support for treatment at notified Centres of Excellence (figures evolved from the original ₹20 lakh Group-1 ceiling).

Policy figures change. Verify current MoHFW / CoE guidance before relying on any amount. Verify

Centres of Excellence (15)
  • All India Institute of Medical Sciences (AIIMS) — New Delhi, Delhi
  • Maulana Azad Medical College — New Delhi, Delhi
  • Sanjay Gandhi Post Graduate Institute of Medical Sciences — Lucknow, Uttar Pradesh
  • Post Graduate Institute of Medical Education and Research (PGIMER) — Chandigarh, Chandigarh
  • Centre for DNA Fingerprinting & Diagnostics with Nizam’s Institute of Medical Sciences — Hyderabad, Telangana
  • King Edward Memorial Hospital — Mumbai, Maharashtra
  • Institute of Post-Graduate Medical Education and Research (IPGMER) — Kolkata, West Bengal
  • Centre for Human Genetics with Indira Gandhi Hospital — Bengaluru, Karnataka
  • Institute of Child Health and Hospital for Children (ICH & HC) — Chennai, Tamil Nadu
  • All India Institute of Medical Sciences (AIIMS) — Jodhpur, Rajasthan
  • Sree Avittam Thirunal Hospital (SAT), Government Medical College — Thiruvananthapuram, Kerala
  • All India Institute of Medical Sciences (AIIMS) — Bhopal, Madhya Pradesh
  • Regional Institute of Medical Sciences (RIMS) — Imphal, Manipur
  • All India Institute of Medical Sciences (AIIMS) — Patna, Bihar
  • Assam Medical College & Hospital — Dibrugarh, Assam

Voluntary contributions / crowdfunding (separate from CoE funding): https://rarediseases.mohfw.gov.in/

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.

("LIG4 syndrome" OR "DNA ligase IV syndrome" OR "SCID with macrocephaly due to DNA ligase IV deficiency" OR "DNA ligase IV deficiency" OR "ligase 4 syndrome") OR (MESH:"LIG4 Syndrome") OR ("LIG4" OR "LIG4-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: LIG4 Syndrome

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

"LIG4 syndrome" OR "DNA ligase IV syndrome" OR "SCID with macrocephaly due to DNA ligase IV deficiency" OR "DNA ligase IV deficiency" OR "ligase 4 syndrome"

Study-type breakdown: 0 interventional · 1 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 (4013) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T06:19:32.006Z