ORPHA:3454
Wieacker-Wolff syndrome
Also known as: Foot contractures-muscle atrophy-oculomotor apraxia syndrome
Publications
679
Trials
0
Interventional, condition-specific
Researchers
1,211
Distinct authors in sample
Gene link
ZC4H2
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
--contractures syndrome, formerly known as Wieacker-Wolff syndrome, is a severe X-linked neurodevelopmental disorder characterized by severe contractures (arthrogryposis) and .
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:0010758
- MeSH:C536703
- MeSH:C537472
- OMIM:314580
- UMLS:C0796200
Additional Mondo synonyms (19)
MCS · MRXS4 · Miles-CARPENTER X-linked mental retardation syndrome · Miles-Carpenter syndrome · WRWF · WRWFXLR · Wieacker Wolff syndrome · Wieacker syndrome · Wieacker-Wolff syndrome, X-linked · Wieacker-Wolff syndrome, X-linked recessive · X-linked intellectual disability, Miles-Carpenter type · ZC4H2-Associated Rare Disorders (ZARD) · apraxia, oculomotor, with congenital contractures and muscle atrophy · contractures of feet, muscle atrophy, and oculomotor apraxia · foot contractures-muscle atrophy-oculomotor apraxia syndrome · intellectual disability-developmental delay-contractures syndrome · mental retardation, X-linked, syndromic 4 · mental retardation, X-linked, with congenital contractures and Low fingertip arches · mental retardation, X-linked, with congenital contractures and low fingertip arches
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 — ZC4H2
- LiteraturePresent
679 matched papers (412 in last 10 years) Source
- Phenotype characterisedPresent
62 HPO annotations (e.g. Abnormal speech pattern; Clinodactyly of the 5th finger; Strabismus) 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 (ZC4H2).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
62
Associated phenotypes · MONDO:0010758
- Abnormal speech pattern
- Clinodactyly of the 5th finger
- Strabismus
- Abnormality of eye movement
- Ptosis
Showing 5 of 62 — 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?
679
679 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.
679 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).
412 in the last 10 years · low confidence
Phrase hits: 154 · MeSH hits: 0
Who's working on it?
1,211
Distinct author names in 154 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.
- 01
- 02Stevenson RE7 papers · 2022
Greenwood Genetic Center and Self Memorial Hospital, SC 29646.
Papers in Europe PMC - 03Zhang L6 papers · 2026
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Papers in Europe PMC - 04Zhang Y6 papers · 2024
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China.
Papers in Europe PMC - 05Kim CH5 papers · 2023
Department of Biology, Chungnam National University, Daejeon, 34134, Republic of Korea. zebrakim@cnu.ac.kr.
Papers in Europe PMC - 06Li F4 papers · 2023
Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming Yunnan 650500, China. leefan623@sina.com.
Papers in Europe PMC - 07Mao B4 papers · 2024
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Papers in Europe PMC - 08Sadikovic B4 papers · 2022
a Department of Pathology and Laboratory Medicine , Western University , London , ON , Canada.
Papers in Europe PMC - 09
- 10Wieacker P4 papers · 2019
Universitäts-Frauenklinik, Freiburg, Federal Republic of Germany.
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 Wieacker-Wolff 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.
("Wieacker-Wolff syndrome" OR "Foot contractures-muscle atrophy-oculomotor apraxia syndrome" OR "MRXS4" OR "Miles-CARPENTER X-linked mental retardation syndrome" OR "Miles-Carpenter syndrome" OR "WRWFXLR" OR "Wieacker Wolff syndrome" OR "Wieacker syndrome" OR "Wieacker-Wolff syndrome, X-linked" OR "Wieacker-Wolff syndrome, X-linked recessive" OR "X-linked intellectual disability, Miles-Carpenter type" OR "ZC4H2-Associated Rare Disorders (ZARD)" OR "apraxia, oculomotor, with congenital contractures and muscle atrophy" OR "contractures of feet, muscle atrophy, and oculomotor apraxia" OR "contractures of the feet, muscle atrophy, and oculomotor apraxia" OR "intellectual disability-developmental delay-contractures syndrome" OR "mental retardation, X-linked, syndromic 4" OR "mental retardation, X-linked, with congenital contractures and Low fingertip arches") OR ("ZC4H2" OR "ZC4H2 syndrome" OR "ZC4H2-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Wieacker-Wolff syndrome" OR "Foot contractures-muscle atrophy-oculomotor apraxia syndrome" OR "MRXS4" OR "Miles-CARPENTER X-linked mental retardation syndrome" OR "Miles-Carpenter syndrome" OR "WRWFXLR" OR "Wieacker Wolff syndrome" OR "Wieacker syndrome" OR "Wieacker-Wolff syndrome, X-linked" OR "Wieacker-Wolff syndrome, X-linked recessive" OR "X-linked intellectual disability, Miles-Carpenter type" OR "ZC4H2-Associated Rare Disorders (ZARD)" OR "apraxia, oculomotor, with congenital contractures and muscle atrophy" OR "contractures of feet, muscle atrophy, and oculomotor apraxia" OR "contractures of the feet, muscle atrophy, and oculomotor apraxia" OR "intellectual disability-developmental delay-contractures syndrome" OR "mental retardation, X-linked, syndromic 4" OR "mental retardation, X-linked, with congenital contractures and Low fingertip arches"
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
Synonyms dropped by stoplist: MCS; WRWF
Confidence reasoning
- Preferred label is multi-word and distinctive
- 2 synonym(s) dropped by stoplist (may under-count)
- "X-linked intellectual disability, Miles-Carpenter type" also appears on ORPHA:85283
- Publication count (679) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-26T23:14:29.741Z