DeCure for VACTERL association, X-linked, with or without hydrocephalus
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for VACTERL association, X-linked, with or without hydrocephalus — 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 moduleVACTERL association, X-linked, with or without hydrocephalus 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 vacterl association, x-linked, with or without hydrocephalus 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
X-linked VACTERL with hydrocephalus is a rare disorder caused by loss-of-function mutations in the gene FANCB, which also underlies Fanconi anaemia complementation group B. Cells from affected males show increased chromosome breakage when exposed to DNA cross-linking agents. By 2011, only five FANCB mutations had been reported in six affected males; a further four families with mutations were then identified, each mutation predicted to truncate the FANCB open reading frame and resulting in highly skewed X-inactivation in unaffected carrier females.
Phenotypic data from six affected males in the 2011 study, combined with published data from 12 patients total, show that the major signs are ventriculomegaly, bilateral absent thumbs and radii, vertebral defects, renal agenesis, and growth retardation. Less frequent findings include brain, pituitary, ear and eye malformations; gastrointestinal atresias (oesophageal, duodenal and anal); tracheoesophageal fistula; lung segmentation defects; and small genitalia. Three of the six patients survived the perinatal period. One boy lived to 2 years 10 months but developed aplastic anaemia and died of renal failure. A 1996 report of two brothers described branchial arch defects not previously noted in VACTERL with hydrocephalus, and the authors argued that the term VACTERL “association” is misleading for these hereditary conditions.
No drug treatment is mentioned in any of these abstracts. The prognosis is poor, with a high rate of perinatal death and the risk of later aplastic anaemia. What is still missing is any clinical trial, any drug repurposing data, any systematic collection of patient samples for drug screening, and any funding for preclinical work on FANCB-related pathways. Without a larger patient cohort and a better understanding of the natural history beyond the perinatal period, there is no basis for even proposing a drug.
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 · 2011 · 51 citations
X‐linked VACTERL with hydrocephalus syndrome: Further delineation of the phenotype caused by <i>FANCB</i> mutations
AbstractX-linked VACTERL-hydrocephalus syndrome (X-linked VACTERL-H) is a rare disorder caused by mutations in the gene FANCB which underlies Fanconi Anemia (FA) complementation group B. Cells from affected males have increased chromosome breakage on exposure to DNA cross-linking agents. Only five FANCB mutations found in six affected males, including an affected uncle and nephew, have been reported. We have identified FANCB mutations in a further four affected families. The VACTERL-H phenotype segregates as an X-linked recessive trait in three of these. Each mutation is predicted to truncate the FANCB open reading frame and results in highly skewed X-inactivation in unaffected carrier females. Phenotypic data were available on six affected males. Comparison of the clinical findings in our patients with published clinical data (total 12 patients) shows that ventriculomegaly, bilateral absent thumbs and radii, vertebral defects, renal agenesis, and growth retardation are the major phenotypic signs in affected males. Less frequent are brain, pituitary, ear and eye malformations, gastrointestinal atresias (esophageal, duodenal and anal), tracheoesophageal fistula, lung segmentation defects, and small genitalia. Three of six of our patients survived the perinatal period. One boy lived up to 2 years 10 months but developed aplastic anemia and died of renal failure. These data show that loss-of-function FANCB mutations result in a recognizable, multiple malformation phenotype in hemizygous males for which we propose clinical criteria to aid diagnosis.
American Journal of Medical Genetics · 1996 · 31 citations
VACTERL with hydrocephalus and branchial arch defects: Prenatal, clinical, and autopsy findings in two brothers
AbstractVACTERL association is defined as a combination of vertebral, anal, cardiac, tracheoesophageal, renal and limb anomalies, in particular radial defects. In recent years hydrocephalus was observed in patients with apparent VACTERL association. This particular condition was recognized as a hereditary entity with poor prognosis. Both autosomal recessive and X-linked forms were described. Here we report prenatal, clinical and autopsy findings in 2 brothers with this syndrome, who had, in addition, branchial arch anomalies. The recurrence in this family suggests X-linked inheritance. Branchial arch defects have so far not been described as part of the VACTERL+H syndrome. This observation further supports that a variety of brain anomalies including hydrocephalus associated with VACTERL anomalies represents separate entities with a considerable recurrence risk. The use of the term VACTERL "association" for these conditions is misleading and is discouraged.
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.
