DeCure for Tibia, hypoplasia or aplasia of, with polydactyly
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tibia, hypoplasia or aplasia of, with polydactyly — 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 moduleTibia, hypoplasia or aplasia of, with polydactyly 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 tibia, hypoplasia or aplasia of, with 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
sonic hedgehog signaling molecule (SHH) — SHH 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 y01drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7E2I · 4.07 Å · ligand CHOLESTEROL HEMISUCCINATE (Y01). Experimental structure, not a prediction.
What the evidence adds up to
A 1996 case report describes a male Bedouin baby with femoral hypoplasia-unusual facies syndrome, including bilateral asymmetrical lower limb hypoplasia or aplasia, short remnants of both femora, absent right tibia, bifid right big toe, dysmorphic facies, thoracic and pelvic abnormalities, macrophallus, and bilateral cryptorchidism. The authors note this association with preaxial polydactyly is rare and suggest the clinical spectrum may include absent tibia and macrophallus. A 2003 case study raises the possibility of a recessive mode of inheritance for tibial aplasia-ectrodactyly, challenging the more widely accepted theory of dominant expression with reduced penetrance, and emphasises the need for thorough prenatal sonographic evaluation even in families without known history.
A 2015 retrospective review of 21 patients (12 male, 9 female) with 30 affected extremities treated for tibial hemimelia between 1998 and 2011 reports a mean age of 4.8 years at initial surgery. Knee level disarticulation was performed in 6 extremities of 4 patients; one patient with type III underwent transtibial amputation. The mean number of surgeries per patient was 6.4, with mean external fixator and casting duration of 17 months. Mean lengthening was 4.9 cm, and mean limb length discrepancy at 5.8 years follow-up was 3.1 cm. SF-10 health survey scores were similar between disarticulated and reconstructed patients, but all scores were significantly higher when disarticulation was performed in cases of knee instability.
The 2015 study concludes that when the knee joint is stable, treatment modality should be chosen according to the presence of the proximal tibia, and that amputation should be preferred in cases of knee joint instability. No drug treatments are mentioned in any of the abstracts. What remains missing are prospective trials comparing surgical approaches with standardised functional outcome measures, larger patient cohorts to clarify inheritance patterns, and any investigation of prenatal or postnatal medical interventions.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 1996 · 23 citations · open access
Femoral hypoplasia-unusual facies syndrome with bifid hallux, absent tibia, and macrophallus: a report of a Bedouin baby.
AbstractA male Bedouin baby with the clinical profile of femoral hypoplasia-unusual facies syndrome is described. The phenotype includes bilateral asymmetrical lower limb hypoplasia/aplasia with short remnants of both femora, absent right tibia, bifid right big toe, dysmorphic facies, thoracic/pelvic abnormalities, macrophallus, and bilateral cryptorchidism. This report re-emphasises the previously described rare association of femoral hypoplasia-unusual facies syndrome with preaxial polydactyly and suggests that the clinical spectrum of the syndrome could be stretched further to accommodate other unusual traits, for example, macrophallus and absent tibia.
Acta Orthopaedica et Traumatologica Turcica · 2015 · 11 citations · open access
Preliminary report on amputation versus reconstruction in treatment of tibial hemimelia
AbstractAbstract Objective: Tibial hemimelia is a rare disorder characterized by the absence or hypoplasia of the tibia with associated rigidity. The aim of this study was to retrospectively evaluate the affectivity of reconstructive surgeries including centralization of the knee-ankle joints and lengthening with Ilizarov principles, as well as physical and functional results of amputation and reconstruction. Methods: This is an IRB-approved retrospective review of all patients diagnosed with tibial hemimelia who required surgery at a single institution between 1998 and 2011. Charts were analyzed for clinical and radiographical findings. At final follow-up, patients underwent physical and radiographic examination. Patients and their parents were asked to complete the SF-10™ health survey (QualityMetric Inc., Lincoln, RI, USA). Results: Twenty-one patients (12 male, 9 female) with 30 affected extremities were included. Mean age was 4.8±3.1 years at initial surgery. Knee level disarticulation was performed in 6 extremities of 4 patients. One patient with type III underwent transtibial amputation. Mean number of surgeries for each patient was 6.4±3.3, and mean duration of external fixator and casting was 17±6 months. Mean lengthening was 4.9±1.3 cm, and mean limb length discrepancy was 3.1±1.7 cm at 5.8±3.7 years at follow-up. SF-10™ scores were similar in disarticulated and reconstructed patients (p=0.63). All scores were significantly higher when disarticulation was performed in cases of knee instability (p<0.01). Conclusion: When stability of the knee joint is present, treatment modality should be chosen according to the existence of the proximal tibia. Amputation should be preferred in cases of knee joint instability. DOI: 10.3944/AOTT.2015.15.0005 Özet Amaç: Tibiyal hemimeli, tibia eksikliğinden veya gelişmemesinden kaynaklanan sert ve nadir bir hastalıktır. Bu çalışmanın amacı, diz-bilek eklemlerinin merkezileştirilmesi ve Ilizarov ilkeleri ile uzatma işlemi de dahil olmak üzere rekonstrüksif ameliyatların etkinliğini geriye dönük olarak değerlendirmekti. Ampütasyon ve rekonstrüksiyonun fiziksel ve işlevsel sonuçları da değerlendirildi.Çalışma planı: Bu, tibiyal hemimeli tanısı koyulan ve 1998-2011 yılları arasında tek bir kuruluşta ameliyata gerek duyulan bütün hastalar üzerinde gerçekleştirilen IRB onaylı geriye dönük incelemedir. Klinik ve radyografik bulgular için grafikler analiz edilmiştir. Dahil edilen bütün hastalar, ek bir fiziksel ve radyografik inceleme amacıyla son takip ziyareti için çağırılmıştır. Ebeveynler ve hastalardan SF-10™ sağlık araştırma formunu doldurmaları istenmiştir.Bulgular: Hastalıktan etkilenen toplam 30 uzuv olmak üzere 21 hasta (12 erkek, 9 kadın) çalışmaya dahil edilmiştir. İlk ameliyatta ortalama yaş 4.8’di (±3.1). 4 hastanın 6 uzvunda diz seviyesinde disartikülasyon yapıldı. Tip III hastalığı olan bir hastaya transtibiyal ampütasyon yapıldı. Her hasta için ortalama ameliyat sayısı 6.4’tü (±3.3) ve dış sabitleyici ve alçının ortalama durma süresi 17 (±6) aydı. Ortalama uzatma 4.9 (±1.3) cm’di ve ortalama uzuv uzunluğu farkı 5.8 (±3.7) yıllık takipte 3.1 (±1.7) cm’di. Eklem yerinden ayırma ve rekonstrüksiyon yapılan hastalarda SF-10™ puanları benzerdi (p=0.63). Ancak, eklem yerinden ayırma işlemi diz dengesizliği bulunan durumlarda uygulandığında, bütün puanlar anlamlı derecede daha yüksekti (p<0.01).Çıkarımlar: Tedavi yöntemi, diz eklemi dengeliyken, proksimal tibianın bulunup bulunmamasına göre seçilmelidir. Diz eklemi dengesizliği varsa ampütasyon tercih edilmelidir
Journal of diagnostic medical sonography · 2003 · 1 citations · open access
Tibial Aplasia-Ectrodactyly in a Nonautosomal Dominant Expression: Implications in Prenatal Sonology Diagnosis
AbstractTibial aplasia-ectrodactyly (TAE) is a syndrome of severe defects of the extremities. Because of its rare occurrence, its inheritance pathway is not clearly understood. The most widely accepted theory is a dominant expression, possibly with reduced penetrance in skipped generations. The case study presented raises the possibility of a recessive mode of inheritance, thus reducing the predictability of its occurrence in a family pedigree. For the physician and sonographer, this illustrates the importance of an understanding of this anomaly and thorough prenatal sonographic evaluation even in unsuspecting families. While the expectation of its occurrence is remote, early diagnosis when it is present expands the management options for the physician and 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.
