DeCure for Short-rib thoracic dysplasia 6 with or without polydactyly
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for short-rib thoracic dysplasia 6 with or without polydactyly — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleShort-rib thoracic dysplasia 6 with or without polydactyly maps to a 8-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 short-rib thoracic dysplasia 6 with or without polydactyly 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
NIMA related kinase 1 (NEK1) — NEK1 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 2-amino-4-methyl-thiazol-5-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4B9D · 1.9 Å · ligand [4-(2-AMINO-4-METHYL-THIAZOL-5-YL)-PYRIMIDIN-2-YL]-(3-NITRO-PHENYL)-AMINE (CK7). Experimental structure, not a prediction.
What the evidence adds up to
Short-rib thoracic dysplasia 6 with or without polydactyly is part of a group of lethal skeletal dysplasias inherited in an autosomal recessive pattern, characterised by markedly short ribs, short limbs, usually polydactyly, and multiple major organ anomalies. Radiological findings from 10 cases show that each fetus or stillbirth has some features of the four established types, and the overlapping phenotypes support the hypothesis that these subtypes are not single entities but part of a continuous spectrum with variable expressivity. A 2019 case report describes a 30-week fetus with short rib polydactyly syndrome type 3 (Verma-Naumoff) presenting thoracic hypoplasia, short limbs, and postaxial polydactyly.
A 2022 study of 10 unrelated Russian children aged 9 days to 9 years with phenotypic signs of short-rib thoracic dysplasia with or without polydactyly used targeted sequencing of 166 skeletal disease genes. Seven patients were diagnosed with type 3, and three unique patients with types 11, 2, and 9 due to mutations in DYNC2H1, DYNC2I2, IFT80, and IFT140 genes respectively. Of 14 detected variants, six were identified for the first time. More than half of cases were due to DYNC2H1 mutation, and differences in clinical severity were shown depending on which region of the gene was mutated. A 2024 report describes a fetus with short-rib thoracic dysplasia and polydactyly that also had atypical severe acro-mesomelic ossification defects; genetic analysis using a skeletal dysplasia panel revealed compound heterozygous variants in DYNC2H1.
No drug treatment is mentioned in any of these abstracts. The literature consists entirely of case series and genetic characterisation studies. What is missing is any clinical trial, any therapy tested in humans or animals, any funding for drug development, and any patient stratification beyond genetic subtype. The disease is lethal in the perinatal period in most described cases, and no intervention has been reported to alter that course.
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 · 2002 · 70 citations
Diagnostic dilemmas in the short rib–polydactyly syndrome group
AbstractThe short rib-polydactyly syndromes are a group of lethal skeletal dysplasias with autosomal recessive inheritance characterized by markedly short ribs, short limbs, usually polydactyly, and multiple anomalies of major organs. At least four types have been recognized. The radiological findings of 10 cases are presented. Each fetus or stillbirth has some of the radiological features of the four established types of short rib-polydactyly syndrome and raises diagnostic dilemmas in differentiating these entities. The overlapping phenotypes of these fetuses supports the previously suggested hypothesis that the different subtypes of the short rib-polydactyly syndrome group are not single entities, but rather part of a continuous spectrum with variable expressivity.
Pediatric Traumatology Orthopaedics and Reconstructive Surgery · 2022 · 2 citations · open access
Сlinical and genetic characteristics of skeletal cyliopathies – short-rib thoracic dysplasia
AbstractBACKGROUND: Ciliopathies include the large group of hereditary diseases caused by mutations in the genes encoding primary cilia components. The largest type of skeletal ciliopathies is short-rib thoracic dysplasia. AIM: This study describes the clinical and genetic characteristics of Russian patients with STRD with or without polydactyly caused by mutations in the genes DYNC2H1, DYNC2I2, IFT80, and IFT140. MATERIALS AND METHODS: A comprehensive examination of 10 unrelated children aged from 9 days to 9 years, with phenotypic signs of short-rib thoracic dysplasia with or without polydactyly, was conducted. The diagnosis was confirmed using genealogical analysis, clinical examination, neurological examination, radiography, and targeted sequencing of a panel consisting of 166 genes responsible for the development of inherited skeletal pathology. RESULTS: As a result of the molecular genetic analysis, four short-rib thoracic dysplasia genetic variants were identified. Seven patients were diagnosed with short-rib thoracic dysplasia type 3, and three unique patients were diagnosed with types 11, 2, and 9 due to mutations in the DYNC2H1 and DYNC2I2, IFT80, and IFT140 genes, respectively. From the 14 detected variants, six were identified for the first time. As in the previously described patient samples, in the analyzed sample, more than half of the cases were due to a mutation in the DYNC2H1 gene, which is responsible for the SRTD type 3. The differences in the severity of clinical manifestations and the disease course in patients with mutations in certain regions of the gene, which have a different effect on its protein product function, have been shown. CONCLUSIONS: The results of this molecular genetic study broaden the spectrum of mutations in the DYNC2H1, DYNC212, and IFT140 genes causing short-rib thoracic dysplasia and confirm the usefulness of the whole-exome sequencing as the most informative method for identifying mutations of the genetically heterogeneous short-rib thoracic dysplasia group.
Human Genome Variation · 2024 · 0 citations · open access
Unclassifiable short-rib thoracic dysplasia diagnosed using targeted gene panel sequencing
AbstractWe report a case of a fetus with short-rib thoracic dysplasia (SRTD) with polydactyly that also presented with atypical severe acro-mesomelic ossification defects. Genetic analysis using massively parallel sequencing of a skeletal dysplasia panel revealed compound heterozygous variants in DYNC2H1. This clinical report highlights the challenges associated with diagnosing the diverse phenotypes in the SRTD group and emphasizes the importance of genetic surveillance with a targeted gene panel for accurate diagnosis.
Oxford University Press eBooks · 2018 · 0 citations
Short-Rib (±Polydactyly) Dysplasias
AbstractThis chapter discusses short-rib (± polydactyly) dysplasias and related disorders and includes discussion on asphyxiating thoracic dysplasia, Ellis van Creveld syndrome, short rib ±polydactyly syndrome (Saldino-Noonan and Verma-Naumoff types), short rib (±polydactyly) syndrome (Majewski type), short rib ±polydactyly syndrome (Beemer-Langer type), cranioectodermal dysplasia, Mainzer-Saldino syndrome, and axial spondylometaphyseal dysplasia. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.
JOURNAL OF CLINICAL AND BIOMEDICAL SCIENCES · 2019 · 0 citations · open access
Case Report Of Short Rib Polydactyly Syndrome
AbstractShort rib polydactyly syndrome (SRPS) is a group of skeletal dysplasias manifested by short-limb dwarfism, short ribs with thoracic dysplasia and polydactyly. SRPS is an inherited autosomal-recessive disorder with dif-ferent prenatal sonographic and postnatal clinical, histological and radiologic findings. In this report, we pre-sent a case of SRPS type 3 (Verma-Naumoff) with thoracic hypoplasia, short limbs and postaxial polydactyly in a 30-week fetus. Keywords: Short rib polydactyly syndrome, Verma-Naumoff, Ultrasonography, Narrow thoracic cage
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.
