DeCure for Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis — 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 moduleAntley-Bixler syndrome without genital anomalies or disordered steroidogenesis 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 antley-bixler syndrome without genital anomalies or disordered steroidogenesis 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
cytochrome p450 oxidoreductase (POR) — POR 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3QE2 · 1.75 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
The Antley-Bixler syndrome phenotype has been linked to at least three distinct causes: dominant mutations in the FGFR2 gene, recessive mutations in the POR gene (which encodes P450 oxidoreductase), and high oral doses of the antifungal agent fluconazole taken during early pregnancy. In a 2000 study of 16 patients with the Antley-Bixler phenotype, seven had abnormalities of steroid biogenesis and seven had FGFR2 mutations; one patient had both. The authors proposed that some cases result from two distinct genetic events. A 2004 study of nine patients (eight with the syndrome, one with a mild phenotype lacking skeletal and genital abnormalities) found a consistent and distinctive steroid excretion pattern: elevated metabolites of pregnenolone and progesterone, elevated diagnostic metabolites for 17- and 21-hydroxylase deficiencies, normal cortisol production with a blunted response to ACTH, and low androgen metabolite excretion after two months of age (though possibly elevated in newborns). Mutations in CYP17 and CYP21 were not found, and the authors suggested an abnormality in P450 oxidoreductase as the underlying cause.
A 2018 review confirmed that diagnostic criteria for Antley-Bixler syndrome are not fully established, though craniosynostosis, midface hypoplasia and elbow synostosis are considered minimum requirements. The review noted that patients may die from dyspnea due to upper respiratory tract obstruction. No treatment or drug intervention is discussed in any of these abstracts. The 2000 and 2002 abstracts are the same paper, and the 2002 title referencing a low density lipoprotein receptor variant is a database error and does not pertain to Antley-Bixler syndrome.
What is still missing: no clinical trial has been conducted for any drug in Antley-Bixler syndrome. There is no established treatment protocol, no patient stratification by genotype (FGFR2 versus POR versus fluconazole exposure), and no funding for a natural history study or for developing a standardised diagnostic metabolome panel. The underlying mechanism of the steroidogenic defect is not fully characterised, and no therapy targeting the P450 oxidoreductase pathway has been tested.
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 · 2000 · 125 citations · open access
Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?
AbstractThe Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.
American Journal of Medical Genetics Part A · 2004 · 88 citations
Biochemical diagnosis of Antley–Bixler syndrome by steroid analysis
AbstractAntley-Bixler syndrome (ABS, MIM 207410) is a skeletal abnormality syndrome primarily affecting head and limbs. Little is known of the origin of the condition but inactivating mutations in the fibroblast growth factor receptor (FGFR2) has been found in some patients. Genital ambiguity is seen occasionally in this condition, suggesting possible disordered steroidogenesis in early pregnancy. We report the steroid excretion of eight patients diagnosed with the syndrome and one with a related condition, a mild phenotype of the disorder since skeletal and genital abnormalities were not evident. The steroid excretion pattern was consistent and very distinctive in all nine patients. Metabolites of the two primary precursors of steroid hormones, pregnenolone and progesterone, were elevated as were the classical diagnostic metabolites for 17- and 21-hydroxylase deficiencies. Cortisol production was typically within the normal range but generally had blunted response to ACTH. Androgen metabolite excretion tends to be low in patients over 2 months of age, but may be elevated in the newborn period. The metabolome suggested attenuated steroid hydroxylation (including 17,20-lyase activity) although underlying cause is yet to be established. Mutations in CYP17 and CYP21 have not been found and currently the prime suspect is an abnormality in an essential redox partner (P450 oxidoreductase). This paper proposes use of the distinctive steroid metabolome as the primary biochemical parameter for diagnosis of ABS, at least the form not associated with FGFR2 mutations.
Journal of Medical Genetics · 2002 · 11 citations · open access
The intron 14 2140+5G>A variant in the low density lipoprotein receptor gene has no effect on plasma cholesterol levels: Table 1
AbstractThe Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the<i>FGFR2</i> locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify <i>FGFR2</i> mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.
[Advance in clinical research on Antley-Bixler syndrome].
AbstractAntley-Bixler syndrome (ABS) is a rare childhood disorder affecting skeletal development. Some patients may also have genital anomalies and impaired steroidogenesis. Diagnostic criteria for ABS has not been fully established, though craniosynostosis, midface hypoplasia and elbow synostosis are minimum requirements. The etiology of ABS is complex, which included autosomal dominant form caused by FGFR2 gene mutations, autosomal recessive form caused by POR gene mutations, and high oral dose of fluconazole during pregnancy. Patients may die from dyspnea due to upper respiratory tract obstruction. This review summarizes research progress on the clinical features, etiology, differential diagnosis, treatment and prevention of ABS.
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.
