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ORPHA:488632

TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome

medium confidenceDisorder

Publications

309

72.5th percentile

Trials

0

Interventional, condition-specific

Researchers

463

Distinct authors in sample

Gene link

TBCK

Definitive

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

A rare multiple anomalies/ syndrome characterized by profound with absent speech, severe with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset , strabismus and post-natal onset of brain atrophy (including loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (including plagio/brachycephaly, bitemporal narrowing, high-arched eyebrows high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features.

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 (5)

IHPRF3 · TBCK ID-syndrome · TBCK syndrome · TBCK-related encephalopathy · hypotonia, infantile, with psychomotor retardation and characteristic facies 3

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.”

3/6 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.

  1. Gene identifiedPresent

    Definitive — TBCK

  2. LiteraturePresent

    309 matched papers (260 in last 10 years) Source

  3. Phenotype characterisedPresent

    188 HPO annotations (e.g. Fetal pyelectasis; Corneal opacity; Nystagmus) Source

  4. Animal modelNot found

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

  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 (TBCK).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

188

Associated phenotypes · MONDO:0014823

  • Fetal pyelectasis
  • Corneal opacity
  • Nystagmus
  • Microcephaly
  • Low-set ears

Showing 5 of 188 — 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)

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?

309

309 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=3967) is 59.

309 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).

260 in the last 10 years · medium confidence · 72.5th percentile (publications denominator)

Phrase hits: 40 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

463

Distinct author names in 40 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
    Angireddy R4 papers · 2026

    Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    Papers in Europe PMC
  2. 02
    Katsura KA4 papers · 2026

    Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA; Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: Kei.Katsura@ucsf.edu.

    Papers in Europe PMC
  3. 03
    Bhoj EJ3 papers · 2026
    Papers in Europe PMC
  4. 04
    Black A3 papers · 2026

    Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    Papers in Europe PMC
  5. 05
    Bhat V2 papers · 2024

    Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.

    Papers in Europe PMC
  6. 06
    Botto LD2 papers · 2025

    Division of Medical Genetics, Dept of Pediatrics, University of Utah, Salt Lake City, UT, USA.

    Papers in Europe PMC
  7. 07
    Ciesielski B2 papers · 2026

    ITMAT, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.

    Papers in Europe PMC
  8. 08
    Díaz A2 papers · 2024

    Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA; Division of Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

    Papers in Europe PMC
  9. 09
    Diaz-Rosado A2 papers · 2026

    Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    Papers in Europe PMC
  10. 10
    Durham EL2 papers · 2026

    Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA.

    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.

medium 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 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 TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism 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.

("TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome" OR "IHPRF3" OR "TBCK ID-syndrome" OR "TBCK syndrome" OR "TBCK-related encephalopathy" OR "hypotonia, infantile, with psychomotor retardation and characteristic facies 3") OR ("TBCK" OR "TBCK-related")

Run this search on Europe PMC

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

"TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome" OR "IHPRF3" OR "TBCK ID-syndrome" OR "TBCK syndrome" OR "TBCK-related encephalopathy" OR "hypotonia, infantile, with psychomotor retardation and characteristic facies 3"

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 multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (309) is high for prevalence class "<1 / 1 000 000" — confidence capped at medium

Ingested 2026-07-27T17:26:51.052Z