Overview
Lethal congenital contracture syndrome type 2 (LCCS2), also known as multiple contracture syndrome, Israeli Bedouin type, is an extremely rare and severe autosomal recessive disorder characterized by multiple joint contractures (arthrogryposis), markedly reduced fetal movements, and early lethality. The condition is caused by mutations in the ERBB3 gene, which encodes a member of the epidermal growth factor receptor family of receptor tyrosine kinases. This gene plays a critical role in the development and survival of motor neurons and Schwann cells during embryonic development. Affected infants typically present at birth with severe arthrogryposis multiplex congenita, including contractures of multiple joints, particularly the limbs. Additional features include micrognathia (small jaw), pulmonary hypoplasia (underdeveloped lungs), pterygia (webbing of the skin across joints), and marked anterior horn cell degeneration in the spinal cord, reflecting a profound loss of lower motor neurons. Fetal akinesia (lack of movement) is a hallmark feature detectable during pregnancy. The condition is invariably lethal, with affected infants either stillborn or dying shortly after birth due to respiratory failure related to pulmonary hypoplasia and neurological compromise. LCCS2 was originally described in consanguineous Israeli Bedouin families. There is currently no curative treatment or disease-modifying therapy available for this condition. Management is limited to supportive and palliative care. Genetic counseling is essential for affected families, and prenatal diagnosis may be possible through molecular testing when the familial mutation is known. The condition belongs to a group of lethal congenital contracture syndromes (LCCS types 1–11) that share overlapping features of fetal akinesia and arthrogryposis but are caused by mutations in different genes.
Also known as:
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Neonatal
Begins at or shortly after birth (first 4 weeks)
FDA & Trial Timeline
3 eventsSalubris Biotherapeutics Inc — PHASE2
Hummingbird Bioscience — PHASE1, PHASE2
M.D. Anderson Cancer Center — PHASE1
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
No FDA-approved treatments are currently listed for Lethal congenital contracture syndrome type 2.
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Rare Disease Specialist
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to Lethal congenital contracture syndrome type 2.
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Start the conversation →Latest news about Lethal congenital contracture syndrome type 2
Disease timeline:
New recruiting trial: Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers, and HMBD-001 + Cetuximab in Advanced Squamous Cell Cancers
A new clinical trial is recruiting patients for Lethal congenital contracture syndrome type 2
New recruiting trial: Study of JK07 in Patients With Chronic Heart Failure
A new clinical trial is recruiting patients for Lethal congenital contracture syndrome type 2
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Common questions about Lethal congenital contracture syndrome type 2
What is Lethal congenital contracture syndrome type 2?
Lethal congenital contracture syndrome type 2 (LCCS2), also known as multiple contracture syndrome, Israeli Bedouin type, is an extremely rare and severe autosomal recessive disorder characterized by multiple joint contractures (arthrogryposis), markedly reduced fetal movements, and early lethality. The condition is caused by mutations in the ERBB3 gene, which encodes a member of the epidermal growth factor receptor family of receptor tyrosine kinases. This gene plays a critical role in the development and survival of motor neurons and Schwann cells during embryonic development. Affected infa
How is Lethal congenital contracture syndrome type 2 inherited?
Lethal congenital contracture syndrome type 2 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Lethal congenital contracture syndrome type 2 typically begin?
Typical onset of Lethal congenital contracture syndrome type 2 is neonatal. Age of onset can vary across affected individuals.
Which specialists treat Lethal congenital contracture syndrome type 2?
3 specialists and care centers treating Lethal congenital contracture syndrome type 2 are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.