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A severe X-linked recessive neurodevelopmental disorder characterized by severe contractures (arthrogryposis) and intellectual disability.
Features include very common findings: Exotropia and Abnormal dermatoglyphics; and common findings: Hypogonadism, Facial asymmetry, Microcornea, and Rocker bottom foot and others. 56 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Brain and nerves | 8 | Mild intellectual disability, Dystonia, Seizure |
Muscles | 7 | Low muscle tone (hypotonia), Generalized hypotonia, Muscle weakness |
Head and neck | 5 | U-Shaped upper lip vermilion, Microcephaly, Facial palsy |
Bones and joints | 5 | Excessive inward curvature of the lower spine (hyperlordosis), Sideways curvature of the spine (scoliosis), Excessive outward curvature of the upper spine (kyphosis) |
Pregnancy and birth | 3 | Congenital foot contractures, Decreased fetal movement, Neonatal respiratory distress |
Skin | 2 | Palmar hyperkeratosis, Abnormal dermatoglyphics |
Lungs and breathing | 2 | Apnea, Neonatal respiratory distress |
Eyes | 2 | Oculomotor apraxia, Ptosis |
Arms and legs | 2 | Congenital foot contractures, Rocker bottom foot |
Growth and development | 1 | Short stature |
Digestive system | 1 | Feeding difficulties |
Hormones | 1 | Hypogonadism |
Age of onset: at birth.
ZC4H2 function has not been fully characterized.
Wieacker-Wolff syndrome is associated with mutations in the ZC4H2 gene on chromosome X.
Genetic testing for ZC4H2 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 2 very common features, 7 common features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for Wieacker-Wolff syndrome.
5 publications have been identified in PubMed for Wieacker-Wolff syndrome. Research spans Case Report / Case Series (80%) and Basic Science / Preclinical (20%).
Masterson EM (2026). [PMID: 41727299](https://pubmed.ncbi.nlm.nih.gov/41727299/). *HeartRhythm Case Rep*. [Case Report / Case Series]
Kobayashi S (2025). [PMID: 39777128](https://pubmed.ncbi.nlm.nih.gov/39777128/). *Clin Pediatr Endocrinol*. [Case Report / Case Series]
Nicoletti M (2025). [PMID: 41322872](https://pubmed.ncbi.nlm.nih.gov/41322872/). *Cureus*. [Case Report / Case Series]
Harris RE (2025). [PMID: 40867536](https://pubmed.ncbi.nlm.nih.gov/40867536/). *Biomolecules*. [Basic Science / Preclinical]
Decio A (2024). [PMID: 38483676](https://pubmed.ncbi.nlm.nih.gov/38483676/). *Neurol Sci*. [Case Report / Case Series]
Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 11:54 AM UTC
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