DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Cenani-Lenz syndactyly syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCenani-Lenz syndactyly syndrome maps to a 1-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 cenani-lenz syndactyly syndrome 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
LDL receptor related protein 4 (LRP4) — LRP4 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8S9P · 3.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Cenani-Lenz syndactyly syndrome is a rare autosomal recessive disorder characterised by oligosyndactyly, metacarpal synostosis, and phalangeal disorganisation, with variable facial and systemic features. Most cases are caused by homozygous or compound heterozygous missense and splice mutations of the LRP4 gene. A 2019 study of a consanguineous family identified a novel missense variant (c.1151A>G; p.Tyr384Cys) in LRP4 via whole exome sequencing; all affected individuals were homozygous and obligate carriers heterozygous for this variant, which was absent from 60,706 exomes and predicted pathogenic by three software tools. The same review notes that C-L-syndrome-like phenotypes can also arise from APC truncating mutations, genomic rearrangements of the GREM1-FMN1 locus, and FMN1 mutations. Surprisingly, patients with APC truncating mutations do not develop polyposis despite increased β-catenin levels.
Mild facial dysmorphism has been described: a 2003 report of two consanguineous families noted a high broad prominent forehead, hypertelorism, depressed nasal bridge, downslanting palpebral fissures, short nose, short prominent philtrum, and malar hypoplasia. One family showed quasidominant inheritance. A 1997 case described a 4.5-year-old boy from a consanguineous Turkish family with synostosis and phalangeal malformations but no radio-ulnar synostosis or foot bone abnormalities; dermatoglyphic analysis was performed and compared with previous reports. A 2008 report describes a patient with complex toe syndactyly, oligodactyly, and atypical facial features resembling Kabuki syndrome but with normal intelligence and an extreme eyelid defect; the authors note that this patient lacks the hand oligodactyly or syndactyly consistently present in all CLS patients and suggest it may represent a new condition.
No treatment trials, no drug interventions, and no survival or response rate data appear in any of these abstracts. The literature is limited to case reports, family studies, and genetic characterisation. What is missing is any clinical trial, any animal model testing of a repurposed drug, any patient stratification beyond genotype, and any funding for therapeutic development in this ultra-rare syndrome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2018 · 27 citations
Cenani–Lenz syndrome and other related syndactyly disorders due to variants in <i>LRP4</i>, <i>GREM1</i>/<i>FMN1</i>, and <i>APC</i>: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways
AbstractCenani-Lenz (C-L) syndrome is characterized by oligosyndactyly, metacarpal synostosis, phalangeal disorganization, and other variable facial and systemic features. Most cases are caused by homozygous and compound heterozygous missense and splice mutations of the LRP4 gene. Currently, the syndrome carries one OMIM number (212780). However, C-L syndrome-like phenotypes as well as other syndactyly disorders with or without metacarpal synostosis/phalangeal disorganization are also known to be associated with specific LRP4 mutations, adenomatous polyposis coli (APC) truncating mutations, genomic rearrangements of the GREM1-FMN1 locus, as well as FMN1 mutations. Surprisingly, patients with C-L syndrome-like phenotype caused by APC truncating mutations have no polyposis despite the increased levels of β catenin. The LRP4 and APC proteins act on the WNT (wingless-type integration site family) canonical pathway, whereas the GREM-1 and FMN1 proteins act on the bone morphogenetic protein (BMP) pathway. In this review, we discuss the different mutations associated with C-L syndrome, classify its clinical features, review familial adenomatous polyposis caused by truncating APC mutations and compare these mutations to the splicing APC mutation associated with syndactyly, and finally, explore the pathophysiology through a review of the cross talks between the WNT canonical and the BMP antagonistic pathways.
Mild facial dysmorphism and quasidominant inheritance in Cenani-Lenz syndrome
AbstractCenani-Lenz syndrome (CLS; MIM 212780) is a rare autosomal recessive syndactyly/synostosis syndrome. No facial dysmorphism was previously noted. We studied two families; in the first an affected female had a previously affected brother and her father was said to have been similarly affected. Extensive inbreeding in this family suggests quasidominant inheritance. In the second family there was a history of a similarly affected sib who, in addition, had genital anomalies and cleft palate. The parents were first cousins. Both probands had similar mild facial dysmorphism; a high broad, prominent forehead, hypertelorism, a depressed nasal bridge, downslanting palpebral fissures, a short nose, a short prominent philtrum and malar hypoplasia. The present report suggests mild facial dysmorphism and quasidominant inheritance in one family with Cenani-Lenz syndrome.
American Journal of Medical Genetics · 1997 · 21 citations · open access
Dermatoglyphics in patients with Cenani-Lenz type syndactyly: Studies in a new case
AbstractWe describe an additional case of Cenani-Lenz syndactylism in a 4 1/2-year-old boy from a consanguineous Turkish family. The digital anomalies consisted partly of synostosis and partly of malformations of the phalanges. Although there was no radio-ulnar synostosis or abnormality of the bones of the feet, the findings are comparable to those described in the Cenani-Lenz type of syndactyly. We analysed the dermatoglyphics of our patient and compared them with those previously reported. We also investigated the relationship between the bony malformations and the dermatoglyphic patterns in our patient and in the literature.
Novel missense alteration in <i>LRP4</i> gene underlies Cenani–Lenz syndactyly syndrome in a consanguineous family
AbstractBACKGROUND: Syndactyly is a clinical feature of split-hand foot malformation (SHFM), ectodermal-dysplasia-syndactyly (EDSS1) and Cenani-Lenz syndactyly syndromes (CLSS). In EDSS1, only cutaneous syndactyly is observed, with sparse hair, abnormal nails and dentition. In SHFM, bony syndactyly may vary from hypoplasia of one phalanx to aplasia of central digits, extending to complete fusion of all fingers and toes in CLSS. Several genes have been assigned to these syndromes. Performing a single step molecular diagnostics becomes a challenge when a phenotype has overlaps with several syndromes or when some of the clinical features are not fully expressed in patients. METHODS: Whole exome sequencing (WES) analysis on one sample derived from a consanguineous family was performed. A causative variant in WES data was prioritized via standard bioinformatics tools. The selected variant was Sanger sequenced in all the available family members for autosomal recessive segregation. RESULTS: A novel missense variant (c.1151A>G; p.Tyr384Cys) was identified in the LRP4 gene. Sanger validation confirmed that all affected individuals were homozygous and the obligate carriers were heterozygous for this variant. The variant is neither reported in 1000 human genomes, nor in 60 706 exomes databases, and is predicted as "pathogenic" by SIFT, Polyphen-2 and MutationTaster software. CONCLUSIONS: The present study broadens the pathogenic spectrum of the LRP4 gene in syndactyly syndromes. WES is a powerful tool for genetic analysis in research and can be readily used as a first-line diagnostic test in syndactyly and related phenotypes.
American Journal of Medical Genetics Part A · 2008 · 3 citations
Complex toe syndactyly with characteristic facial phenotype: A new syndrome?
AbstractNonsyndromic syndactyly is a common, heterogeneous hereditary condition of webbed fingers and toes that can be cutaneous or bony, unilateral or bilateral. We describe a patient with complex toe syndactyly and oligodactyly, some interesting skeletal hand findings and atypical facial features without other case like this described before. Cenani-Lenz syndrome (CLS) is a rare disorder with total syndactyly and irregular synostosis of carpal, metacarpal and phalanges, it may involve ulna and radius and digital rays may be absent, some of these were described with atypical facial features and one patient had renal hypoplasia and vertebral anomalies but our patient does not have the oligodactyly or syndactyly of the hands that is consistently present in all patients with CLS. The atypical facial features of our patient resemble Kabuki syndrome but oligodactyly and complex syndactyly have not been described in Kabuki syndrome and this patient has normal intelligence, and extreme eyelid defect (resembling ablepharon). Therefore, for our patient, we suggested to treat in a new condition of limb anomalies and atypical face.
Dermatoglyphics in patients with Cenani-Lenz type syndactyly: Studies in a new case
AbstractWe describe an additional case of Cenani-Lenz syndactylism in a 41/2-year-old boy from a consanguineous Turkish family. The digital anomalies consisted partly of synostosis and partly of malformations of the phalanges. Although there was no radio-ulnar synostosis or abnormality of the bones of the feet, the findings are comparable to those described in the Cenani-Lenz type of syndactyly. me analysed the dermatoglyphics of our patient and compared them with those previously reported. We also investigated the relationship between the bony malformations and the dermatoglyphic patterns in our patient and in the literature. Am. J. Med. Genet. 70:341-345, 1997. (C) 1997 Wiley-Liss, Inc.
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.
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