DeCure for Klippel-Feil syndrome 2, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Klippel-Feil syndrome 2, autosomal recessive — 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 moduleKlippel-Feil syndrome 2, autosomal recessive 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 klippel-feil syndrome 2, autosomal recessive 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.
What the evidence adds up to
Klippel-Feil syndrome is defined by a congenital defect in the formation or segmentation of the cervical spine, and the clinical triad of short neck, low posterior hairline, and limited neck movement is described. The condition is heterogeneous, with numerous associated abnormalities of other organ systems. One 2008 case report notes an extremely rare association with situs inversus, and a 2021 case report repeats this finding of Klippel-Feil syndrome with situs inversus totalis, suggesting the two genetically heterogeneous conditions may share a common causative agent. The 2004 review states that pedigree analysis has identified a human genetic locus for the disease, and mouse models point to the PAX gene family and Notch signalling pathway as possible candidates, but it also notes that it remains unclear whether Klippel-Feil syndrome is a discrete entity or part of a spectrum of congenital spinal deformities.
A 2021 study of 25 patients (mean age 12.9 years, 15 male, 10 female) found that limited cervical range of motion was the most common clinical feature, occurring in 12 cases (48%). Using multigene panel sequencing, the study detected 11 pathogenic missense mutations in eight patients, in the genes COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB. No pathogenic mutations were found in five previously reported KFS-associated genes: GDF6, MEOX1, GDF3, MYO18B, and RIPPLY2. The study also reported that patients with multiple contiguous cervical fusions (Samartzis type III) had a significantly higher proportion of short neck and limited cervical range of motion compared to type I and type II.
No drug treatment or intervention is mentioned in any of these abstracts. The 2004 review states that treatment regimes vary from modification of activities to extensive spinal surgeries, but no pharmacological therapy is discussed. The 2021 genetic study mentions targeted therapy only as a future goal, not as an existing option. What is still missing is any clinical trial of a drug for Klippel-Feil syndrome, any validated molecular target for a repurposed compound, and a clear understanding of whether the genetic heterogeneity can be stratified into subgroups that might respond to different approaches.
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 · 2004 · 252 citations
Klippel-Feil Syndrome
AbstractKlippel-Feil syndrome occurs in a heterogeneous group of patients unified only by the presence of a congenital defect in the formation or segmentation of the cervical spine. Numerous associated abnormalities of other organ systems may be present. This heterogeneity requires comprehensive evaluation of all patients and treatment regimes that can vary from modification of activities to extensive spinal surgeries. This also has made delineation of diagnostic and prognostic classes difficult and has complicated elucidation of the genetic etiology of the syndrome. Furthermore, it is unclear whether Klippel-Feil syndrome is a discrete entity, or if it is one point on a spectrum of congenital spinal deformities. Pedigree analysis has identified a human genetic locus for the disease. Mouse models suggest members of the PAX gene family and Notch signaling pathway as possible etiologic candidates. Only by identifying the link between the genetic etiology and the phenotypic pathoanatomy of Klippel-Feil syndrome will we be able to rationalize the heterogeneity of the syndrome.
Klippel-Feil syndrome with situs inversus--a rare association.
AbstractKlippel-Feil Syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae. The clinical triad consists of short neck, low posterior hairline and limited neck movement. Multiple congenital anomalies have been associated with this disease. This is a case of KFS in a young girl along with situs inversus, which is an extremely rare association. Various systemic associations occurring in this multi-system disorder are also discussed.
BMJ Case Reports · 2021 · 2 citations · open access
Rare association of Klippel-Feil syndrome with situs inversus totalis and review of the genetic background
AbstractKlippel-Feil syndrome (KFS) is a rare congenital anomaly in forming the cervical vertebrae resulting in the fusion of two or more of the vertebrae. KFS is associated with many congenital anomalies, some of which are common and well known. Here, we report a child with an extremely rare association of KFS with situs inversus totalis (SIT). Both KFS and SIT are genetically heterogeneous and their co-occurrence suggests a high possibility of sharing the same underlying causative agent. Here, we review the genetic background that is known for these two conditions in the literature.
World Journal of Advanced Research and Reviews · 2022 · 2 citations · open access
Klippel-Feil syndrome associated with congenital megacolon: a case report
AbstractKlippel-Feil syndrome is a congenital abnormality characterized by the fusion of the bones of the cervical spine. Its association with a gastrointestinal abnormality is rare. We report a case of a 14-year-old girl affected by Klippel-Feil syndrome associated with congenital megacolon. Klippel-Feil syndrome should be considered as any polymalformative syndrome and its management should be multidisciplinary.
[Clinical Characteristics and Genetic Analysis of Klippel-Feil Syndrome].
AbstractObjective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.
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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