DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for orofaciodigital syndrome 18 — 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 moduleOrofaciodigital syndrome 18 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 orofaciodigital syndrome 18 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
Orofaciodigital syndrome type I has the highest incidence among the thirteen described types. A 2012 case report describes a nine-year-old girl admitted for an unrelated complaint whose oral and digital anomalies led to ultrasound detection of polycystic kidneys. The authors note that physicians should be aware of life-threatening anomalies possibly associated with the syndrome. A 2007 study of twin girls diagnosed with OFD type I identified a previously unreported missense mutation H81Q in the OFD1 gene, corresponding to a nucleotide change 243C>G in exon 3. A 2020 report describes an Indian child with sparse hair, facial milia, and absence of the corpus callosum, in whom next-generation sequencing found a frameshift pathogenic variant in exon 13 of the OFD1 gene.
A 2014 report describes a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas, features similar to variant forms called congenital heart defects, hamartomas of the tongue and polysyndactyly (OMIM 217085) and orocardiodigital syndrome. Whole exome sequencing showed compound heterozygosity for a frameshift mutation and a likely pathogenic sequence variant in WDPCP, a gene regulating planar cell polarity and ciliogenesis. Genotyping of parents and unaffected siblings was consistent with autosomal recessive inheritance. The authors suggest disruption of planar cell polarity and ciliogenesis may result in this unusual form of orofaciodigital syndrome.
A 1989 report describes a patient with orofaciodigital syndrome type IV, characterised by lobulated tongue, pseudo-cleft of lip, pre- and postaxial polydactyly of hands and feet, severe talipes equinovarus, mesomelic limb shortness with tibial hypoplasia, and severe bilateral deafness. Five similar cases including this patient were on record at that time, and autosomal recessive inheritance was considered likely.
No drug treatment is mentioned in any of these abstracts. What is missing for orofaciodigital syndrome type 18 specifically is any clinical trial, any preclinical drug study, any patient-derived cell work, and any funded research programme aimed at therapy. The genetic basis is heterogeneous, with at least two genes (OFD1, WDPCP) implicated in different subtypes, and the rarity of each type means no stratified patient cohort exists for a trial. No repurposing candidate 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.
American Journal of Medical Genetics Part A · 2014 · 32 citations
Compound heterozygosity for a frame shift mutation and a likely pathogenic sequence variant in the planar cell polarity—ciliogenesis gene <i>WDPCP</i> in a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas
AbstractWe report on a young girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. These features are similar to those reported in individuals with variant forms of orofaciodigital syndrome known as congenital heart defects, hamartomas of the tongue and polysyndactly (CHDHTP: OMIM 217085) [Örstavik et al., 1992] and orocardiodigital syndrome [Digilio et al., 1996]. Whole exome sequencing revealed that she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP, a gene that regulates planar cell polarity and ciliogenesis. Results of genotyping in her parents and unaffected siblings were consistent with autosomal recessive inheritance of the mutation and the WDPCP variant. These results suggest that disruption of planar cell polarity and ciliogenesis may result in this unusual form of orofaciodigital syndrome.
American Journal of Medical Genetics · 1989 · 22 citations
Orofaciodigital syndrome type IV: Report of a patient
AbstractWe describe a further patient with the orofaciodigital syndrome type IV. The clinical characteristics include lobulated tongue, pseudo-cleft of lip, pre- and postaxial polydactyly of hands and feet, severe talipes equinovarus, mesomelic limb shortness associated with tibial hypoplasia, and severe bilateral deafness. Five similar cases including the present patient are now on record. Autosomal recessive inheritance is likely.
The Cleft Palate-Craniofacial Journal · 2007 · 13 citations
Buccal Anomalies, Cephalometric Analysis and Genetic Study of Two Sisters with Orofaciodigital Syndrome Type I
AbstractOrofaciodigital syndromes have many clinical and cephalometric anomalies, including facial irregularities, oral cavity abnormalities, and malformations of fingers and toes. In this case of twin girls, buccal exploration, cephalometric examination, and genetic analysis were performed to diagnose Orofaciodigital I or Orofaciodigital II syndrome. Clinically, the twins had several dental and skeletal irregularities. Genetic analysis revealed a DNA segment abnormality corresponding to exon 3 and presence of nucleotide change, 243C>G, leading to the missense mutation H81Q. This causative mutation associated with the OFD1 gene has not been reported previously. Both patients were diagnosed as having Orofaciodigital I syndrome.
Ear Nose & Throat Journal · 2012 · 6 citations · open access
Orofaciodigital Syndrome
AbstractOrofaciodigital syndrome is a very rare entity with X-linked dominant inheritance characterized by oral, facial, and digital anomalies. Thirteen different types have been described in the literature to date. Of these, orofaciodigital syndrome type I has the highest incidence. Renal and central nervous system malformations may accompany the oral, facial, and digital anomalies. We report a case of orofaciodigital syndrome type I in a 9-year-old girl. The patient was admitted with a complaint unrelated to the syndrome. The coexistence of an oral anomaly with a digital anomaly in this patient led us to search for other possible anomalies. Ultrasonography revealed a diagnosis of polycystic kidneys. Physicians must be mindful of the external appearance of patients with this syndrome and be aware of life-threatening anomalies possibly associated with it.
American Journal of Medical Genetics Part A · 2020 · 0 citations
Indian child with novel variant in <scp>OFD1</scp> gene
AbstractOrofaciodigital syndrome (OFD) can have variable phenotype and presents with oral anomalies, facial dysmorphism, and digital malformations like syndactyly, and polydactyly. Other presentations also include renal and cardiac defects, and central nervous system anomalies like hydrocephalus and cerebellar abnormalities. OFD1 is a X-linked dominant form of the syndrome presenting in females with mutations in CXorf5 or OFD1 gene. We describe a young child with sparse hairs, milia over face and absence of corpus callosum. Next generation sequencing showed frameshift pathogenic variant in the exon 13 of the OFD1 gene, consistent with diagnosis of OFD1.
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.
