ORPHA:496641
Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
Publications
1,424
Trials
0
Interventional, condition-specific
Researchers
105
Distinct authors in sample
Gene link
TBCD, TBCE
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare, severe early-onset neurodegenerative characterized mainly by (DD) / developmental regression (DR), , cortical atrophy, secondary hypomyelination and thin corpus callosum. Additional features include secondary microcephaly, , spasticity, optic atrophy and skeletal anomalies.
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:0044646
- OMIM:617193
- UMLS:C5567454
Additional Mondo synonyms (3)
PEBAT · encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum · encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum; PEBAT
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.
- Gene identifiedPresent
Definitive — TBCD, TBCE
- LiteraturePresent
1,424 matched papers (926 in last 10 years) Source
- Phenotype characterisedPresent
112 HPO annotations (e.g. Hypoplasia of the corpus callosum; Global developmental delay; Respiratory failure) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- 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 (TBCD, TBCE).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
112
Associated phenotypes · MONDO:0044646
- Hypoplasia of the corpus callosum
- Global developmental delay
- Respiratory failure
- Absent smooth pursuit
- Feeding difficulties
Showing 5 of 112 — 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?
1,424
1,424 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.
1,424 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).
926 in the last 10 years · low confidence
Phrase hits: 14 · MeSH hits: 0
Who's working on it?
105
Distinct author names in 14 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.
- 01Aguilera-Albesa S1 paper · 2023
Paediatric Neurology Unit, Department of Paediatrics, Hospital Universitario de Navarra, Navarrabiomed, 31008 Pamplona, Spain.
Papers in Europe PMC - 02Akbaş S1 paper · 2025
Istanbul Medical Faculty, Department of Medical Genetics, Istanbul University, Istanbul, Turkey.
Papers in Europe PMC - 03Akiel MA1 paper · 2023
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
Papers in Europe PMC - 04Al Tuwaijri A1 paper · 2023
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
Papers in Europe PMC - 05AlBlawi MA1 paper · 2023
King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.
Papers in Europe PMC - 06Aldriwesh MG1 paper · 2023
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
Papers in Europe PMC - 07AlEissa M1 paper · 2023
Department of Molecular Genetics, Public Health Laboratory, Public Health Authority, Riyadh, Saudi Arabia.
Papers in Europe PMC - 08Alfares A1 paper · 2023
King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.
Papers in Europe PMC - 09Aljawfan G1 paper · 2023
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
Papers in Europe PMC - 10Almutairi M1 paper · 2023
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia.
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.
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 60 · after dedupe 59 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 59 · 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 (59)
- ctis·2026-526821-16-00·Authorised·Melanoma-TBK1-inhibitor enhanced Immuno Therapy with Checkpoint Inhibitors: a Phase IB/II Trial in Unresectable Stage III or Stage IV Cutaneous Melanoma
skipped — LLM skipped (--skip-llm)
- ctis·2026-526225-18-00·Authorised·A phase I/IIa safety, dose finding and feasibility trial of CD30/CEA CART in patients with liver metastases from CEA positive colorectal adenocarcinoma
skipped — LLM skipped (--skip-llm)
- ctis·2026-525260-18-00·Authorised·Open-label, single-center, single-arm phase 2 futility trial evaluating the oral indapamide for reducing progression of disability in people with primary and secondary progressive multiple sclerosis (MS)
skipped — LLM skipped (--skip-llm)
- ctis·2026-525566-21-00·Authorised, ongoing·A phase IIa, single-arm, single-center, open label, proof-of-concept trial evaluating increased frequency dosing of VCN-01 (zabilugene almadenorepvec) in combination with nab-Paclitaxel/Gemcitabine (GnP) in Patients with Newly-Diagnosed Metastatic Pancreatic Cancer (VIRAGE2)
skipped — LLM skipped (--skip-llm)
- ctis·2026-526167-38-00·Authorised·ALBUMINUS: Dose reduction of human albumin during large-volume paracentesis in patients with cirrhosis
skipped — LLM skipped (--skip-llm)
- ctis·2025-524322-18-00·Authorised·A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing Orelabrutinib to Placebo in Patients With Non-Active Secondary Progressive Multiple Sclerosis
skipped — LLM skipped (--skip-llm)
- ctis·2025-522275-28-00·Authorised·Sample Collection Study to Monitor the Risk of Malignancy Due to Insertional Oncogenesis in Early Onset Patients with Metachromatic Leukodystrophy Treated with OTL-200 in the Clinical Development Program
skipped — LLM skipped (--skip-llm)
- ctis·2025-524048-36-00·Authorised·Paclitaxel plus ramucirumab and tislelizumab as switch maintenance versus continuation of chemotherapy and tislelizumab in patients with advanced HER2-negative and PD-L1 positive gastroesophageal adenocarcinoma: the ARMANI-2/ENGIC08 trial by GONO
skipped — LLM skipped (--skip-llm)
- ctis·2025-522373-10-00·Authorised·IM0271016: An Open-label, Multi-center, Long-term Extension Study to Evaluate the Long-term Safety and Tolerability of Admilparant in Participants with Pulmonary Fibrosis
skipped — LLM skipped (--skip-llm)
- ctis·2024-511296-15-00·Authorised, recruiting·A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of each of two dose levels of sarilumab in adults with early polymyalgia rheumatica
skipped — LLM skipped (--skip-llm)
- ctis·2025-524095-27-00·Authorised·A Phase 2, Open-Label, Multicenter, Randomized Study to Evaluate Denikitug as Monotherapy or in Combination With Nivolumab or Chemotherapy in Participants With HER2-Negative, Unresectable, Recurrent, and/or Metastatic Gastric, Gastroesophageal Junction (GEJ), and Esophageal Adenocarcinomas
skipped — LLM skipped (--skip-llm)
- ctis·2025-523984-39-00·Authorised·A Phase 2, Open Label, Multicenter, Randomized Study, to Evaluate the Efficacy and Safety of Denikitug Monotherapy and Denikitug-based Combinations in Participants With Advanced Microsatellite Stable (MSS) Colorectal Cancer (CRC).
skipped — LLM skipped (--skip-llm)
- ctis·2026-525817-29-00·Authorised·A Phase 2a Study of SUN-627 to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Impact on Measures of Neuroinflammation in the Central Nervous System in Participants With Non-Active Progressive Multiple Sclerosis (SPMS/PPMS)
skipped — LLM skipped (--skip-llm)
- ctis·2025-523670-17-00·Authorised, recruiting·Multinational, Interventional, 52-week, Open-label, Single-arm
Study to Evaluate the Treatment Outcomes of Anifrolumab 120 mg
Subcutaneous Once Weekly in Immunosuppressant-naïve and
Biologic-naïve Systemic Lupus Erythematosus (SUNFLOWER)
skipped — LLM skipped (--skip-llm)
- ctis·2025-524062-16-00·Authorised·A Phase 3 Multicenter, Open-label Study to Assess the Long-term Safety and Tolerability of KarXT in Adolescents (13 to 17 years of age) with Schizophrenia and KarXT+KarX-EC in Children and Adolescents (5 to 17 years of age) with Irritability Associated with Autism Spectrum Disorder
skipped — LLM skipped (--skip-llm)
- ctis·2025-523555-66-00·Authorised·A Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (DAK539) and Ruxolitinib vs. Placebo and Ruxolitinib in Adult Patients with Myelofibrosis who are JAK inhibitor naive
skipped — LLM skipped (--skip-llm)
- ctis·2025-521982-29-00·Authorised·UNLOCK - EPIBREAST, a phase II study of prifetrastat (PF-07248144), a KAT6 inhibitor, plus fulvestrant for advanced HR+/HER2- breast cancer with biomarkers analysis
skipped — LLM skipped (--skip-llm)
- ctis·2025-525013-23-00·Authorised, recruiting·A Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study of EIK1001 in Combination with Pembrolizumab and Chemotherapy in Participants with Stage 4 Non-Small Cell Lung Cancer (TeLuRide-008).
skipped — LLM skipped (--skip-llm)
- ctis·2025-525005-20-00·Authorised·A Multicenter Randomized Controlled Trial Assessing the Efficacy and Safety of Recombinant Human Follicle Stimulating Hormone (r-hFSH-alfa originator) and Human Chorionic Gonadotropin (hCG) in Enhancing Sperm Concentration in Men with Oligozoospermia, Low Testosterone, and Normal FSH Serum Levels (APHRODITE Group 3): A Collaborative Research Initiative
skipped — LLM skipped (--skip-llm)
- ctis·2025-523389-26-00·Authorised, recruiting·A Phase 3, Multi-regional, Open-label, Randomized Study of Tirabrutinib vs Rituximab and Temozolomide in Participants with Relapsed/Refractory Primary Central Nervous System Lymphoma
skipped — LLM skipped (--skip-llm)
- ctis·2025-523134-28-00·Authorised·A national randomised multi-centre phase II/III trial using MesoPher in ABC borderline resectable pancreatic cancer (PREOPANC-6 trial)
skipped — LLM skipped (--skip-llm)
- ctis·2025-524876-43-00·Authorised·HO183 CAR T: A phase III randomized trial comparing academically produced BCMA-directed CAR T-cells (ARI0002h) with standard of care regimen in patients with relapsed/refractory multiple myeloma
skipped — LLM skipped (--skip-llm)
- ctis·2025-520842-31-00·Authorised·ANTIPROM - Comparison of two prophylactic antibiotic regimens in case of preterm prelabor rupture of membranes before 34 weeks of gestation: a randomized controlled trial
skipped — LLM skipped (--skip-llm)
- ctis·2025-524373-17-00·Authorised·MERCURE study: MEthotrexate in ReCurrent dVIN
skipped — LLM skipped (--skip-llm)
- ctis·2025-524031-39-00·Authorised·Phase I study of CDK8 inhibitor RVU120 in combination with everolimus in children with recurrent or progressive Group 3 or 4 medulloblastoma; MEDWAY
skipped — LLM skipped (--skip-llm)
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 Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome — check Associations / patient organisations on that page.
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.
("Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome" OR "PEBAT" OR "encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum" OR "encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum; PEBAT") OR ("TBCD" OR "TBCD syndrome" OR "TBCD-related" OR "TBCE" OR "TBCE syndrome" OR "TBCE-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome" OR "PEBAT" OR "encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum" OR "encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum; PEBAT"
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 (1424) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-27T17:34:45.406Z