Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy
Lethal congenital contracture syndrome type 2 is a rare arthrogryposis syndrome characterized by multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cell degeneration, skeletal muscle atrophy (mainly in the lower limbs), presence of a markedly distended urinary bladder and absence of hydrops, pterygia and bone fractures. Other craniofacial (e.g. cleft palate, facial palsy) and ocular (e.g. anisocoria, retinal detachment) anomalies may be additionally observed. The disease is usually neonatally lethal however, survival into adolescence has been reported.
Data assembled from 6 of 12 sources · Last updated Sep 18, 2026, 8:20 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center
Features include sometimes findings: Ventricular septal defect and Enlarged and weakened heart (dilated cardiomyopathy). 13 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Muscles | 2 | Skeletal muscle atrophy, Joint stiffness present at birth (arthrogryposis multiplex congenita) |
Heart and blood vessels | 2 | Ventricular septal defect, Enlarged and weakened heart (dilated cardiomyopathy) |
Bones and joints | 1 | Skeletal muscle atrophy |
Pregnancy and birth | 1 | Decreased fetal movement |
Lungs and breathing | 1 | Respiratory failure |
Age of onset: infancy.
ERBB3 encodes erb-b2 receptor tyrosine kinase 3 (1,342 aa). Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Highest expression in Nerve Tibial (116.8 TPM) and Skin Sun Exposed Lower leg (71.9 TPM).
Lethal congenital contracture syndrome 2 is associated with mutations in the ERBB3 gene on chromosome 12.
ERBB3 is classified as a druggable target (Clinically Actionable, Drug Resistance, Druggable Genome, Enzyme, Kinase, and Tyrosine Kinase categories) with score 4.0.
Genetic testing for ERBB3 is available. Testing is considered confirmatory for diagnosis.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for lethal congenital contracture syndrome 2.
6 publications have been identified in PubMed for lethal congenital contracture syndrome 2. Research spans Case Report / Case Series (67%), Basic Science / Preclinical (17%), and Gene Therapy / Novel Therapeutics (17%).
Caluianu M (2026). [PMID: 41686830](https://pubmed.ncbi.nlm.nih.gov/41686830/). *PLoS One*. [Gene Therapy / Novel Therapeutics]
Jacob M (2026). [PMID: 40497796](https://pubmed.ncbi.nlm.nih.gov/40497796/). *Brain*. [Basic Science / Preclinical]
Velardo D (2026). [PMID: 42211024](https://pubmed.ncbi.nlm.nih.gov/42211024/). *Front Genet*. [Case Report / Case Series]
Poudel P (2025). [PMID: 41413000](https://pubmed.ncbi.nlm.nih.gov/41413000/). *Br J Dermatol*. [Case Report / Case Series]
Yang S (2024). [PMID: 38602424](https://pubmed.ncbi.nlm.nih.gov/38602424/). *Connect Tissue Res*. [Case Report / Case Series]
Hatjis CG (2024). [PMID: 40321344](https://pubmed.ncbi.nlm.nih.gov/40321344/). *Case Rep Perinat Med*. [Case Report / Case Series]