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ORPHA:329235

X-linked central congenital hypothyroidism with late-onset testicular enlargement

low confidenceDisorder

Also known as: IGSF1 deficiency syndrome · X-linked central congenital hypothyroidism with late-onset macroorchidism

Publications

767

Trials

0

Interventional, condition-specific

Researchers

453

Distinct authors in sample

Gene link

IGSF1

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

X-linked central hypothyroidism with late-onset testicular enlargement is a rare, genetic, endocrine disease characterized by central hypothyroidism, testis enlargement in adolescence resulting in adult macroorchidism, delayed pubertal testosterone rise with a subsequent delayed pubertal growth spurt, small thyroid gland, and variable prolactin and growth hormone deficiency.

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 (4)

CHTE · Immunoglobulin superfamily member 1 deficiency syndrome · hypothyroidism Central and testicular enlargement · hypothyroidism, central, and testicular enlargement, 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.”

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 — IGSF1

  2. LiteraturePresent

    767 matched papers (562 in last 10 years) Source

  3. Phenotype characterisedPresent

    5 HPO annotations (e.g. Inappropriately normal thyroid-stimulating hormone level; Reduced circulating prolactin concentration; Hypothyroidism) Source

  4. Animal modelPresent

    1 genotype model (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 (IGSF1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

5

Associated phenotypes · MONDO:0010475

  • Inappropriately normal thyroid-stimulating hormone level
  • Reduced circulating prolactin concentration
  • Hypothyroidism
  • Overweight
  • Reduced TSH response to thyrotrophin-releasing hormone stimulation test

Animal models (Monarch / Alliance)

1

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?

767

767 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.

767 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).

562 in the last 10 years · low confidence

Phrase hits: 38 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

453

Distinct author names in 38 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
    Bernard DJ13 papers · 2022

    Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.

    Papers in Europe PMC
  2. 02
    Wit JM13 papers · 2023

    Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.

    Papers in Europe PMC
  3. 03
    Joustra SD12 papers · 2023

    Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands.

    Papers in Europe PMC
  4. 04
    Oostdijk W9 papers · 2020

    Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.

    Papers in Europe PMC
  5. 05
    Biermasz NR8 papers · 2020

    Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.

    Papers in Europe PMC
  6. 06
    Lynch S8 papers · 2020

    Genealogical Society of Ireland, Dún Laoghaire, Ireland

    Papers in Europe PMC
  7. 07
    Farrar G7 papers · 2020

    Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin, Ireland

    Papers in Europe PMC
  8. 08
    Treacy E7 papers · 2020

    Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin, Ireland

    Papers in Europe PMC
  9. 09
    Turgeon MO7 papers · 2020

    Departments of Anatomy and Cell Biology & Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

    Papers in Europe PMC
  10. 10
    Fliers E6 papers · 2021

    Department of Pediatrics (S.D.J., J.M.W., W.O.), Department of Medicine (S.D.J., N.R.B., A.M.P.), Division of Endocrinology, Department of Clinical Chemistry and Laboratory Medicine (B.E.P.B.), and Department of Clinical Genetics (M.L.), Leiden University Medical Center, 2300 C Leiden, The Netherlands; Department of Pediatric Endocrinology (C.A.H., A.S.P.v.T.), Emma Children's Hospital, and Department of Endocrinology and Metabolism (C.A.H., E.F.), Academic Medical Center, University of Amsterdam, 1100 DE, The Netherlands; University of Cambridge Metabolic Research Laboratories (N.S.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge DB2 2OO, United Kingdom; Division of Endocrine and Metabolic Disorders (M.B.), Instituto di Ricovero e Cura a Carettere Scientifico, Instituto Auxologica Italiano, 20132 Milan, Italy; Department of Clinical Sciences and Community Health (M.B., L.P.), Università degli Studi di Milano, 20122 Milan, Italy; Department of Pharmacology and Therapeutics (M.-O.T., D.J.B.), McGill University, Montréal, Québec, Canada H9X 3V9.

    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.

Broader category central congenital hypothyroidism also has no matched interventional trial. See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.

Broader category: central congenital hypothyroidism

0

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Parent-category matching found a broader label but no interventional trials under it. How we count trials.

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 X-linked central congenital hypothyroidism with late-onset testicular enlargement — 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 central congenital hypothyroidism with late-onset testicular enlargement" OR "IGSF1 deficiency syndrome" OR "X-linked central congenital hypothyroidism with late-onset macroorchidism" OR "Immunoglobulin superfamily member 1 deficiency syndrome" OR "hypothyroidism Central and testicular enlargement" OR "hypothyroidism, central, and testicular enlargement, X-linked recessive") OR ("IGSF1" OR "IGSF1 syndrome" OR "IGSF1-related")

Run this search on Europe PMC

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

"X-linked central congenital hypothyroidism with late-onset testicular enlargement" OR "IGSF1 deficiency syndrome" OR "X-linked central congenital hypothyroidism with late-onset macroorchidism" OR "Immunoglobulin superfamily member 1 deficiency syndrome" OR "hypothyroidism Central and testicular enlargement" OR "hypothyroidism, central, and testicular enlargement, X-linked recessive"

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

Parent-category trials query:

"central congenital hypothyroidism"

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

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: CHTE

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (767) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T13:46:59.816Z