ORPHA:329235
X-linked central congenital hypothyroidism with late-onset testicular enlargement
Also known as: IGSF1 deficiency syndrome · X-linked central congenital hypothyroidism with late-onset macroorchidism
Publications
38
41.8th percentile
Trials
0
Interventional, condition-specific
Researchers
453
Distinct authors in sample
Gene link
IGSF1
Definitive
Readiness
2/6
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0010475
- OMIM:300888
- UMLS:C3550963
- NCIT:C130989
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.”
2/6 stages with a signal
No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.
- Gene identifiedPresent
Definitive — IGSF1
- LiteraturePresent
38 matched papers (27 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- 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)
Not enriched in this build — Monarch phenotype joins were not run for this record.
Animal models (Monarch / Alliance)
Not enriched in this build.
Literature
Is anyone studying this?
38
38 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=5449) is 41.
38 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).
27 in the last 10 years · medium confidence · 41.8th percentile (publications denominator)
Phrase hits: 38 · MeSH hits: 0
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.
- 01Bernard 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 - 02Wit 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 - 03Joustra SD12 papers · 2023
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands.
Papers in Europe PMC - 04Oostdijk W9 papers · 2020
Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.
Papers in Europe PMC - 05Biermasz 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 - 06
- 07Farrar G7 papers · 2020
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin, Ireland
Papers in Europe PMC - 08Treacy E7 papers · 2020
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin, Ireland
Papers in Europe PMC - 09Turgeon MO7 papers · 2020
Departments of Anatomy and Cell Biology & Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Papers in Europe PMC - 10Fliers 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. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial.
Data as of 27 July 2026
No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.
medium confidence · 36.5th 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.
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
- NCT06728735·RECRUITING·Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism With in Situ Thyroid
Conditions: Congenital Hypothyroidism·Matched via recall expansion
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
India — NPRD
Last verified 2026-07-26This 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"
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" OR "IGSF1" OR "permanent congenital hypothyroidism"
Recall-expansion terms: IGSF1, permanent congenital hypothyroidism
Study-type breakdown: 0 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.
Parent-category trials query:
"central congenital hypothyroidism"
Query health: ok — strategies attempted: phrase, recall-expansion; with hits: phrase, recall-expansion
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
Ingested 2026-07-27T13:46:59.816Z