DeCure for Lethal congenital contracture syndrome 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lethal congenital contracture syndrome 1 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLethal congenital contracture syndrome 1 maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for lethal congenital contracture syndrome 1 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
GLE1 RNA export mediator (GLE1) — GLE1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6B4J · 3.4 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
Lethal congenital contracture syndrome 1 is a specific form of arthrogryposis, a birth defect that occurs in approximately one in 3,000 births. Over 150 conditions are known in which multiple congenital contractures are a predominant sign. In a Finnish epidemiological study covering 1987 to 2002, 39 cases of lethal congenital contracture syndrome (LCCS) were identified among 214 cases of multiple contractures. LCCS was characterised by total immobility of the fetus at all ultrasound examinations from 12 weeks onward, multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. The prevalence of LCCS in Finland was 1 in 25,250 births (0.40 per 10,000 births), and it was noted as a unique Finnish disorder and a major cause of lethal arthrogryposis in that population. Of the 214 total cases, 92 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy.
A separate 2022 report described a Chinese pedigree with lethal congenital contracture syndrome type 7 (LCCS7), a genetically distinct form. Whole-exome sequencing on fetal tissue and parental blood identified homozygous nonsense c.3718C>T (p.Arg1240Ter) variants of the CNTNAP1 gene in the fetus, inherited from both parents. This variant was previously unreported and was classified as pathogenic. The couple had experienced polyhydramnios during three pregnancies and had given birth to two liveborns with limb contracture, dyspnea, and neonatal death. The finding enabled genetic counselling and prenatal diagnosis for that family.
No drug treatment is mentioned in any of these abstracts. There is no evidence of any intervention that alters the course of lethal congenital contracture syndrome 1 or any related lethal arthrogryposis. What is missing is any trial design, any patient stratification beyond genetic diagnosis, and any funding directed toward a therapeutic approach rather than genetic counselling and prenatal detection.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Orthopaedics and Related Research · 1985 · 143 citations
Genetic Aspects of Arthrogryposis
AbstractMultiple congenital contractures or arthrogryposis is a birth defect that occurs in approximately one in 3000 births. It can be seen in isolation or in association with other abnormalities. The etiologic and genetic basis of multiple congenital contractures is very heterogeneous. In order to understand the genetic basis and natural history of a specific case, a specific diagnosis must be made. Over 150 conditions are known in which multiple congenital contractures are a predominant sign. In this chapter, the emphasis is on a systematic differential diagnosis and consideration of empiric recurrent risk figures if a specific diagnosis cannot be reached.
American Journal of Medical Genetics Part A · 2006 · 74 citations
Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland—An epidemiological study
AbstractArthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.
Congenital Cutaneous Defects as Complications in Surviving Co-twins
AbstractBACKGROUND: During twin pregnancies, several complications may result in the death of a co-twin depending on the date of death. We describe herein 2 infant survivors of monozygotic twin pairs with 2 distinct possible complications: a aplasia cutis congenita and Volkmann ischemic contracture. OBSERVATIONS: One infant had extensive aplasia cutis congenita with an associated monozygotic co-twin who died at 3 months of gestation, and the other child had a localized arm defect due to Volkmann ischemic contracture and brain damage, with a co-twin who died at approximately 6 weeks of gestation. CONCLUSIONS: Congenital cutaneous defects may result in the death of a co-twin. The most common of these defects is aplasia cutis congenita associated with a fetus papyraceus or a dead fetus related to ischemic/thrombotic events in the placenta and fetus. Volkmann ischemic contracture is rare in the newborn but can cause neonatal cutaneous defects. The cause of Volkmann ischemic contracture in newborns is unknown; however, our second observation suggests the possible role of a dead fetus.
Journal of Pediatric Orthopaedics · 1985 · 31 citations
GENETIC ASPECTS OF ARTHROGRYPOSIS
AbstractMultiple congenital contractures or arthrogryposis is a birth defect that occurs in approximately one in 3000 births. It can be seen in isolation or in association with other abnormalities. The etiologic and genetic basis of multiple congenital contractures is very heterogeneous. In order to understand the genetic basis and natural history of a specific case, a specific diagnosis must be made. Over 150 conditions are known in which multiple congenital contractures are a predominant sign. In this chapter, the emphasis is on a systematic differential diagnosis and consideration of empiric recurrent risk figures if a specific diagnosis cannot be reached.
The case of missing skin: Congenital Volkmann ischemic contracture
AbstractCongenital Volkmann ischemic contracture (CVIC) is an exceedingly rare neonatal compartment syndrome caused by intrauterine ischemia and external compression. It presents at birth with necrotic cutaneous lesions and neurologic impairment, typically in a distal upper extremity. Diagnosis and treatment are often delayed in neonates, leading to long-term neurologic sequelae. We present a rare case of CVIC in order to raise awareness of its presentation and management in hopes of improving outcomes.
[Analysis of CNTNAP1 gene variants in a Chinese pedigree affected with lethal congenital contracture syndrome type 7].
AbstractOBJECTIVE: To explore the genetic basis for a couple who had developed polyhydramnios during three pregnancies and given birth to two liveborns featuring limb contracture, dyspnea and neonatal death. METHODS: Whole-exome sequencing (WES) was carried out on fetal tissue and peripheral blood samples from the couple. Suspected variants were verified by Sanger sequencing. RESULTS: The fetus was found to harbor homozygous nonsense c.3718C>T (p.Arg1240Ter) variants of the CNTNAP1 gene, which were respectively inherited from its mother and father. The variant was unreported previously. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION: The novel homozygous nonsense variants of the CNTNAP1 gene probably underlay the lethal congenital contracture syndrome type 7 (LCCS7) in this pedigree. Above finding has enabled genetic counseling and prenatal diagnosis for the family.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
