ORPHA:457351
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
Also known as: Microcephaly-intellectual disability-sensorineural deafness-epilepsy-abnormal muscle tone syndrome
Publications
44
43.6th percentile
Trials
0
Interventional, condition-specific
Researchers
29
Distinct authors in sample
Gene link
AFG2A
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare genetic disease characterized by microcephaly, global , , abnormal muscle tone, and sensorineural hearing impairment. Additional variable manifestations include , cortical visual impairment, gastrointestinal disturbances, growth restriction, scoliosis, as well as immunodeficiency and thrombocytopenia. Brain imaging may show cerebral atrophy, thin corpus callosum, and hypomyelination.
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:0014698
- OMIM:616577
- UMLS:C4225276
Additional Mondo synonyms (2)
microcephaly-intellectual disability-sensorineural deafness-epilepsy-abnormal muscle tone syndrome · neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities
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 — AFG2A
- LiteraturePresent
44 matched papers (36 in last 10 years) Source
- Phenotype characterisedPresent
78 HPO annotations (e.g. Inability to walk; Strabismus; Gastroesophageal reflux) 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 (AFG2A).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
78
Associated phenotypes · MONDO:0014698
- Inability to walk
- Strabismus
- Gastroesophageal reflux
- Severe intellectual disability
- Failure to thrive
Showing 5 of 78 — 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?
44
44 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.
44 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).
36 in the last 10 years · high confidence · 43.6th percentile (publications denominator)
Phrase hits: 5 · MeSH hits: 0
Who's working on it?
29
Distinct author names in 5 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.
- 01Alonso-Colmenero I1 paper · 2026
Early-Onset and Genetic Epilepsies Unit, Neurology and Neurophysiology Department, Hospital Sant Joan de Déu, University of Barcelona, Esplugues de Llobregat, Barcelona, Spain.
Papers in Europe PMC - 02Álvarez VG1 paper · 2026
Early-Onset and Genetic Epilepsies Unit, Neurology and Neurophysiology Department, Hospital Sant Joan de Déu, University of Barcelona, Esplugues de Llobregat, Barcelona, Spain.
Papers in Europe PMC - 03Arzimanoglou A1 paper · 2026
Early-Onset and Genetic Epilepsies Unit, Neurology and Neurophysiology Department, Hospital Sant Joan de Déu, University of Barcelona, Esplugues de Llobregat, Barcelona, Spain.
Papers in Europe PMC - 04Braun F1 paper · 2026
Institute of Human Genetics, University Hostpital Essen, University Duisburg-Essen, Essen, Germany.
Papers in Europe PMC - 05Camacho AR1 paper · 2026
Early-Onset and Genetic Epilepsies Unit, Neurology and Neurophysiology Department, Hospital Sant Joan de Déu, University of Barcelona, Esplugues de Llobregat, Barcelona, Spain.
Papers in Europe PMC - 06Cantalupo G1 paper · 2026
Innovation Biomedicine Section, Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy.
Papers in Europe PMC - 07Chenyue Z1 paper · 2025
Department of Cytogenetic Laboratory, Children's Hospital of Shanxi, Women Health Center of Shanxi, Taiyuan, China.
Papers in Europe PMC - 08Chilavert VD1 paper · 2026
Early-Onset and Genetic Epilepsies Unit, Neurology and Neurophysiology Department, Hospital Sant Joan de Déu, University of Barcelona, Esplugues de Llobregat, Barcelona, Spain.
Papers in Europe PMC - 09Dai Y1 paper · 2025
State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China.
Papers in Europe PMC - 10Fernández LA1 paper · 2026
Neurology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain.
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.
high 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 57 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 57 · 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 (57)
- ctis·2026-525162-21-00·Authorised·A Phase 2a, multi centric, open label clinical study to explore the safety and tolerability, the pharmacokinetics and pharmacodynamics profile and first signs of efficacy of PTI5803 administered as adjunctive therapy with a 3-dose escalation regimen in patients >= 14 years of age with drug-resistant seizures associated to focal cortical dysplasia, followed by an optional open-label extension study.
skipped — LLM skipped (--skip-llm)
- ctis·2026-526581-24-01·Authorised·Oral versus Intravenous Tranexamic Acid for Blood Loss Prevention in Off-Pump Coronary Artery Bypass Surgery: A
Randomised Non-Inferiority Trial (TRANSCAB Study)
skipped — LLM skipped (--skip-llm)
- ctis·2025-521506-17-01·Authorised·iSTOP-CP: intranasal Stem Cells to treat Perinatal brain injury to combat Cerebral Palsy
skipped — LLM skipped (--skip-llm)
- ctis·2026-525770-19-00·Authorised, ongoing·Optimising the protocol of labour induction using misoprostol – randomised open-label clinical trial (OPTIMISO)
skipped — LLM skipped (--skip-llm)
- ctis·2025-525153-39-00·Authorised·Effect of vasopressin versus norepinephrine on post-operative mean pulmonary arterial pressure following pulmonary endarterectomy surgery, a randomized open label trial
skipped — LLM skipped (--skip-llm)
- ctis·2025-523157-34-00·Authorised, recruiting·A Phase 3 randomized, double-blind, placebo-controlled, parallel group, multicenter study with open-label extension to evaluate the efficacy and safety of fenfluramine hydrochloride in study participants with Rett syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2025-524195-29-00·Authorised·A randomized, placebo-controlled trial to assess the efficacy, tolerability, and pharmacokinetics of clemastine in children and adults with Pitt-Hopkins syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2025-524038-24-00·Authorised, recruiting·A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Seizures
skipped — LLM skipped (--skip-llm)
- ctis·2025-523709-13-00·Authorised·Sevoflurane vs. propofol for general Anesthesia in patients with acute ischemic stroke treated with endoVascular treatmEnt (SAVE trial)
skipped — LLM skipped (--skip-llm)
- ctis·2024-515663-59-00·Authorised·Efficacy of prophylactic levetiracetam for improving functional outcome in the acute phase of intracerebral haemorrhage:
a randomised, double-blind, placebo-controlled, phase 3 trial
PEACH 2
skipped — LLM skipped (--skip-llm)
- ctis·2025-523475-33-00·Authorised, ongoing·Caffeine Administration for Preterms: Pharmacokinetics, Utilization and Correlation Inhibiting Nociception Outcome
skipped — LLM skipped (--skip-llm)
- ctis·2025-522346-46-00·Authorised, ongoing·Study of Oral MC-1 for the Treatment of Patients with PNPO Deficiency
skipped — LLM skipped (--skip-llm)
- ctis·2024-512261-14-00·Authorised, ongoing·A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Vosoritide in Infants and Young Children with Hypochondroplasia, Aged 0 to < 36 Months
skipped — LLM skipped (--skip-llm)
- ctis·2025-520587-18-00·Authorised, ongoing·RENAISSANCE 2:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of SPN-817 in Adults with Focal Onset Seizures
skipped — LLM skipped (--skip-llm)
- ctis·2024-519133-29-00·Authorised·Efficacy of probenecid on cluster seizures during dosage reduction of Anti Seizure Medication (ASM) in presurgical focal epilepsy video-EEG monitoring
skipped — LLM skipped (--skip-llm)
- ctis·2025-521640-38-00·Authorised, ongoing·Open Label Extension Clinical Trial of Vormatrigine in Adult Patients with Epilepsy.
skipped — LLM skipped (--skip-llm)
- ctis·2024-519555-28-00·Authorised, recruiting·EMPEROR: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel Group, Phase 3 Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen (STK-001) in Patients with Dravet Syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2024-514974-39-00·Authorised, ongoing·A Phase 3, Open-Label Study to Investigate the Long-Term Safety and Efficacy of LP352 in the Treatment of Seizures in Children and Adults with Developmental and Epileptic Encephalopathy
skipped — LLM skipped (--skip-llm)
- ctis·2024-516412-17-00·Expired·A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Investigate the Efficacy, Safety, and Tolerability of LP352 in the Treatment of Seizures in Children and Adults with Developmental and
Epileptic Encephalopathies
skipped — LLM skipped (--skip-llm)
- ctis·2024-516148-24-00·Authorised, ongoing·A phase III, randomized, double-blinded study of the efficacy and safety of LEvetiracetam to prevent Seizures in Symptomatic Alzheimer's Disease in adults with Down syndrome (the LESS-AD trial).
skipped — LLM skipped (--skip-llm)
- ctis·2024-516410-38-00·Authorised, ongoing·PDH-RAVICTI - A PHASE II, MULTICENTRIC, PROSPECTIVE, NON-COMPARATIVE CLINICAL TRIAL TO ASSESS THE EFFICACY AND SAFETY OF THE TREATMENT OF PYRUVATE DEHYDROGENASE DEFICIENCY (PDH) PATIENTS WITH GLYCEROL PHENYLBUTYRATE (RAVICTI®)
skipped — LLM skipped (--skip-llm)
- ctis·2024-517061-16-01·Cancelled·An Open Label Clinical Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adult Patients with Focal Onset or Primary Generalized Tonic-Clonic Seizures
skipped — LLM skipped (--skip-llm)
- ctis·2024-514499-42-00·Authorised, recruiting·A Double-Blind, Randomized, Placebo and Active Controlled Study to Evaluate the Efficacy and Safety of Once Daily, Extended Release Levetiracetam as Add-on Therapy in Patients with Refractory Partial Onset Epilepsy.
skipped — LLM skipped (--skip-llm)
- ctis·2024-514045-11-00·Cancelled·A Phase I, Open-Label, Pharmacokinetic, Dose-Escalation Study of Cenobamate (YKP3089) in Pediatric Subjects with Partial Onset Seizures
skipped — LLM skipped (--skip-llm)
- ctis·2024-520171-27-00·Authorised, ongoing·Treatment with full-spectrum cannabis extract of refractory epilepsy associated with Tuberous Sclerosis Complex (TSC): SPECTRUM
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 Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone 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.
("Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome" OR "Microcephaly-intellectual disability-sensorineural deafness-epilepsy-abnormal muscle tone syndrome" OR "neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities") OR ("AFG2A" OR "AFG2A syndrome" OR "AFG2A-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome" OR "Microcephaly-intellectual disability-sensorineural deafness-epilepsy-abnormal muscle tone syndrome" OR "neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities"
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
Ingested 2026-07-27T16:50:23.895Z