DeCure for Klippel-Feil syndrome 3, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Klippel-Feil syndrome 3, autosomal dominant — 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 3, autosomal dominant 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 3, autosomal dominant 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 congenital fusion of cervical vertebrae, with the classic triad of short neck, low posterior hairline, and limited neck movement. 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, present in 12 cases (48%). Patients with multiple contiguous cervical fusions (Samartzis type III) had significantly higher rates of short neck and limited motion than those with type I or type II. That study used multigene panel sequencing and found no pathogenic mutations in the five previously reported KFS genes (GDF6, MEOX1, GDF3, MYO18B, RIPPLY2). Instead, it identified 11 pathogenic missense mutations in eight patients, in genes including COL6A1, COL6A2, CDAN1, GLI3, FLNB, CHRNG, MYH3, POR, and TNXB.
A 2024 case report describes a 6-year-old girl with clinically diagnosed KFS and normal cognition who carried a de novo frameshift variant in PUF60 (c.1179del, p.Ile394Serfs*7). PUF60 loss-of-function is usually associated with Verheij syndrome and intellectual disability, but this patient had no clear learning difficulties. The authors propose that PUF60 should be considered in the differential diagnosis of KFS, and that normal cognition should not rule out testing for it.
Case reports document rare associations. A 2008 report describes a young girl with KFS and situs inversus. A 2022 report describes a 15-year-old girl with KFS who presented with fever, shortness of breath, tricuspid regurgitation, and cardiopulmonary distress secondary to a dysplastic thoracic cage and spine; the authors note that patients with KFS are at increased risk for infection and cardiovascular problems. Another 2022 report describes a 14-year-old girl with KFS and congenital megacolon, calling the gastrointestinal association rare. The authors of these case reports emphasise that KFS is a multisystem disorder requiring multidisciplinary management, and that delay in diagnosis can be fatal.
What is still missing is a clear genetic explanation for most cases: the 2021 panel study found no mutations in the five classical KFS genes and identified candidate variants in only 8 of 25 patients. No targeted therapy exists. Larger cohorts, whole-exome or whole-genome sequencing, and functional studies of newly implicated genes like PUF60, COL6A, and CDAN1 are needed. Patient stratification by fusion type and associated anomalies may clarify prognosis, but systematic natural history data are lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PubMed · 2008 · 4 citations
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.
Annals of Medicine and Surgery · 2022 · 3 citations · open access
Klippel Feil Syndrome presenting with tricuspid regurgitation and cardiopulmonary distress secondary to dysplastic thoracic cage and spine: A case report
AbstractBackground: Klippel Feil syndrome is a rare multifactorial disease that occurs due to a combination of genetic and environmental factors. It is a complex disease that requires lifelong treatment by multidisciplinary teams. Case report: We present a case of a 15-year-old girl who presented with fever and shortness of breath and was found to have Klippel Feil Syndrome with a unique presentation of tricuspid regurgitation with cardiopulmonary distress secondary to dysplastic thoracic cage and spine. Discussion: Patients with Klippel feil syndrome are at increased risk for infection and cardiovascular problems. Proper surgical and medical management are required for patient wellbeing. Delay in diagnosis and management can be fatal with worse outcome
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.
American Journal of Medical Genetics Part A · 2024 · 1 citations · open access
<i>PUF60</i> loss‐of‐function with normal cognition should be considered in the differential diagnosis of Klippel–Feil syndrome
AbstractKlippel-Feil syndrome (KFS) has a genetically heterogeneous phenotype with six known genes, exhibiting both autosomal dominant and autosomal recessive inheritance patterns. PUF60 is a nucleic acid-binding protein, which is involved in a number of nuclear processes, including pre-mRNA splicing, apoptosis, and transcription regulation. Pathogenic variants in this gene have been described in Verheij syndrome due to either 8q24.3 microdeletion or PUF60 single-nucleotide variants. PUF60-associated conditions usually include intellectual disability, among other findings, some overlapping KFS; however, PUF60 is not classically referred to as a KFS gene. Here, we describe a 6-year-old female patient with clinically diagnosed KFS and normal cognition, who harbors a heterozygous de novo variant in the PUF60 gene (c.1179del, p.Ile394Serfs*7). This is a novel frameshift variant, which is predicted to result in a premature stop codon. Clinically, our patient demonstrates a pattern of malformations that matches reported cases of PUF60 variants; however, unlike most others, she has no clear learning difficulties. In light of these findings, we propose that PUF60 should be considered in the differential diagnosis of KFS and that normal cognition should not exclude its testing.
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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