ORPHA:1568
X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome
Also known as: Pettigrew Syndrome · AP1S2-related neurodevelopmental disorder · AP1S2-related X-linked intellectual disability
Publications
1,120
Trials
0
Interventional, condition-specific
Researchers
376
Distinct authors in sample
Gene link
AP1S2
Definitive
Readiness
4/6
Stages with a signal
Clinical definition (Orphanet)
A rare central nervous system characterized by severe intellectual deficit, early with progression to spasticity and contractures, choreoathetosis, , face (long face with prominent forehead), and brain imaging abnormalities such as Dandy-Walker , and iron deposition.
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:0010574
- OMIM:304340
- UMLS:C0796254
- NCIT:C124839
Additional Mondo synonyms (11)
MRX59 · MRXS21 · Pettigrew syndrome · Pettigrew syndrome, X-linked recessive · X-linked intellectual disability 59 · X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome · X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behaviour syndrome · intellectual disability, X-linked syndromic 5 · syndromic X-linked intellectual disability 21 · syndromic X-linked intellectual disability fried type · syndromic X-linked intellectual disability type 5
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.
- Gene identifiedPresent
Definitive — AP1S2
- LiteraturePresent
1,120 matched papers (721 in last 10 years) Source
- Phenotype characterisedPresent
68 HPO annotations (e.g. Mandibular prognathia; Open mouth; Short chin) Source
- Animal modelPresent
1 genotype model (Mus musculus) Source
- 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 (AP1S2).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
68
Associated phenotypes · MONDO:0010574
- Mandibular prognathia
- Open mouth
- Short chin
- Gait disturbance
- Long nose
Showing 5 of 68 — open Monarch for the full list.
Animal models (Monarch / Alliance)
1
Model associations linked to this Mondo ID
- Ap1s2tm1Pschu/Ap1s2tm1Pschu [background:] involves: 129P2/OlaHsd * C57BL/6·MGI:5661462·Mus musculus
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?
1,120
1,120 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.
1,120 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).
721 in the last 10 years · low confidence
Phrase hits: 49 · MeSH hits: 0
Who's working on it?
376
Distinct author names in 49 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.
- 01Schwartz CE3 papers · 2013Papers in Europe PMC
- 02
- 03Wang J3 papers · 2024
Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renminnan Road, Chengdu, 610041, Sichuan, China.
Papers in Europe PMC - 04Bonifacino JS2 papers · 2019
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland 20892, USA; email: juan.bonifacino@nih.gov.
Papers in Europe PMC - 05Dobyns WB2 papers · 2014
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Papers in Europe PMC - 06Li Q2 papers · 2025
Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renminnan Road, Chengdu, 610041, Sichuan, China.
Papers in Europe PMC - 07Pandya HA2 papers · 2020
Department of Botany, Bioinformatics and Climate Change Impacts Management, School of Sciences, Gujarat University, Ahmedabad, India.
Papers in Europe PMC - 08Strahle JM2 papers · 2024
Division of Pediatric Neurosurgery, St. Louis Children's Hospital, Washington University in St. Louis, St. Louis, MO, USA.
Papers in Europe PMC - 09Sun Y2 papers · 2026
Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Papers in Europe PMC - 10Wang H2 papers · 2020
Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renminnan Road, Chengdu, 610041, Sichuan, China.
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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-29
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 intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures 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.
("X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome" OR "Pettigrew Syndrome" OR "AP1S2-related neurodevelopmental disorder" OR "AP1S2-related X-linked intellectual disability" OR "MRX59" OR "MRXS21" OR "Pettigrew syndrome, X-linked recessive" OR "X-linked intellectual disability 59" OR "X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome" OR "X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behaviour syndrome" OR "intellectual disability, X-linked syndromic 5" OR "syndromic X-linked intellectual disability 21" OR "syndromic X-linked intellectual disability fried type" OR "syndromic X-linked intellectual disability type 5") OR ("AP1S2" OR "AP1S2 syndrome" OR "AP1S2-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome" OR "Pettigrew Syndrome" OR "AP1S2-related neurodevelopmental disorder" OR "AP1S2-related X-linked intellectual disability" OR "MRX59" OR "MRXS21" OR "Pettigrew syndrome, X-linked recessive" OR "X-linked intellectual disability 59" OR "X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome" OR "X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behaviour syndrome" OR "intellectual disability, X-linked syndromic 5" OR "syndromic X-linked intellectual disability 21" OR "syndromic X-linked intellectual disability fried type" OR "syndromic X-linked intellectual disability type 5"
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
- "X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome" also appears on ORPHA:85329
- Publication count (1120) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-26T17:44:55.774Z