DeCure for Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 — 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 moduleShort stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 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 short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 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
bone morphogenetic protein 2 (BMP2) — BMP2 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 ndgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2GOO · 2.2 Å · ligand 2-acetamido-2-deoxy-alpha-D-glucopyranose (NDG). Experimental structure, not a prediction.
What the evidence adds up to
In a 2011 study of 186 children and young adults with mutation-proven cardio-facio-cutaneous (CFC) syndrome, BRAF mutations were found in about 75% (140 individuals) and MEK1 or MEK2 mutations in about 25% (46 individuals). Age ranged from 6 months to 32 years. Pulmonary stenosis was the only cardiac anomaly that showed a statistically significant genotype–phenotype correlation, being more common in those with a BRAF mutation. The authors note that 10–30% of individuals with a clinical diagnosis of CFC have no mutation found in the known causative genes.
Geleophysic dysplasia, described in fewer than 40 patients worldwide, is characterised by short stature, a characteristic facial phenotype, micromelia, joint contracture, and early cardiac valvular involvement. A 2013 report of three Saudi sisters with autosomal recessive geleophysic dysplasia documented different levels of severity of cardiac involvement among them. No numbers for survival or response to any treatment are given.
A 2021 case series from India describes short stature syndromes including Noonan syndrome, Williams syndrome, and Silver-Russell syndrome (SRS). SRS incidence is up to 1 in 100,000. The authors note that growth hormone therapy has been used to improve height gain in SRS patients, but provide no efficacy data from their own series. Noonan syndrome patients present with short stature with or without cardiac defect, and multiple autosomal dominant genetic variants contribute. The series reports that next-generation sequencing is identifying more genetic disorders causing short stature in different ethnic populations, such as Kabuki syndrome and Nance-Horan syndrome.
What is still missing: large, prospective natural history studies that stratify patients by specific gene mutation; standardised cardiac and growth outcome measures; and funding for trials that test any intervention against placebo or standard care in genetically defined subgroups.
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 C Seminars in Medical Genetics · 2011 · 94 citations · open access
Cardio‐facio‐cutaneous syndrome: Does genotype predict phenotype?
AbstractCardio-facio-cutaneous (CFC) syndrome is a sporadic multiple congenital anomalies/mental retardation condition principally caused by mutations in BRAF, MEK1, and MEK2. Mutations in KRAS and SHOC2 lead to a phenotype with overlapping features. In approximately 10–30% of individuals with a clinical diagnosis of CFC, a mutation in one of these causative genes is not found. Cardinal features of CFC include congenital heart defects, a characteristic facial appearance, and ectodermal abnormalities. Additional features include failure to thrive with severe feeding problems, moderate to severe intellectual disability and short stature with relative macrocephaly. First described in 1986, more than 100 affected individuals are reported. Following the discovery of the causative genes, more information has emerged on the breadth of clinical features. Little, however, has been published on genotype–phenotype correlations. This clinical study of 186 children and young adults with mutation-proven CFC syndrome is the largest reported to date. BRAF mutations are documented in 140 individuals (approximately 75%), while 46 (approximately 25%) have a mutation in MEK 1 or MEK 2. The age range is 6 months to 32 years, the oldest individual being a female from the original report [Reynolds et al. (1986); Am J Med Genet 25:413–427]. While some clinical data on 136 are in the literature, 50 are not previously published. We provide new details of the breadth of phenotype and discuss the frequency of particular features in each genotypic group. Pulmonary stenosis is the only anomaly that demonstrates a statistically significant genotype–phenotype correlation, being more common in individuals with a BRAF mutation.
Cardiac involvement in geleophysic dysplasia in three siblings of a Saudi family
AbstractGeleophysic dysplasia is an extremely rare acromelic skeletal dysplasia resembling lysosomal storage disease. It is characterised by characteristic facial phenotype, short stature, micromelia, joint contracture, and early cardiac valvular involvement. It has been described worldwide in <40 patients. Herein, we describe the cardiac features in three Saudi sisters with proved autosomal recessive geleophysic dysplasia who showed different levels of severity of their cardiac involvement.
Journal of Pediatric Genetics · 2021 · 2 citations · open access
Short Stature Syndromes: Case Series from India
AbstractSyndromes causing short stature include Noonan syndrome (NS), Williams syndrome, and Silver-Russell syndrome (SRS). SRS is a primordial dwarfism with genetic heterogeneity. The SRS children present with prenatal growth retardation, neonatal hypoglycemia, feeding difficulties, physical asymmetry, with scoliosis and cardiac defect in some cases. The incidence is up to 1 in 100,000. Uniparental disomy, methylation abnormalities, and variants in some genes have been found underlying such phenotype. Growth hormone therapy has been used to improve the height gain in these patients. NS has genetic heterogeneity and most patients present with short stature with or without cardiac defect. Multiple genetic variants, mostly autosomal dominant, contribute to the phenotype. With the availability of next-generation sequencing, more and more genetic disorders causing short stature are being identified in different ethnic populations like Kabuki syndrome and Nance-Horan syndrome. Here, we present some cases of SRS and other additional syndromes with dysmorphism seen in past 5 years.
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.
