DeCure for Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2
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 2 — 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 2 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 2 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
A 19-year-old male with frontometaphyseal dysplasia had a heart murmur since birth, 50–60% bilateral hearing loss, marked supraorbital ridge, wide nasal bridge, and small pointed chin; his parents and siblings were normal and consanguinity was denied. A 10-year-old boy with Floating-Harbor syndrome (short stature, very delayed bone age, expressive language delay, characteristic facial changes) had tetralogy of Fallot with atrial septal defect; prior to that report only one patient with pulmonic stenosis had been described in that syndrome.
Two unrelated patients with severe short stature resistant to growth hormone treatment were found to have de novo heterozygous FBN1 mutations (p.Tyr1696Asp and p.Cys1748Ser). Both had short hands and feet and joint limitation, but one had severe cardiac involvement while the other had tracheal stenosis requiring tracheostomy. The authors concluded that patients with severe dwarfism, skeletal anomalies, and features such as tracheal stenosis or cardiac valvulopathy should be tested for acromelic dysplasia syndromes.
A father and two daughters with short stature, craniofacial dysmorphism, and digital anomalies carried a heterozygous pathogenic BMP2 variant. The youngest daughter had a more severe phenotype; reanalysis of her exome data revealed a second, de novo likely pathogenic DVL1 variant, producing a blended phenotype of autosomal dominant Robinow syndrome plus the familial BMP2-related features. In a case series from India, short stature syndromes including Silver-Russell syndrome (prenatal growth retardation, neonatal hypoglycaemia, feeding difficulties, asymmetry, scoliosis, cardiac defect in some cases) and Noonan syndrome (short stature with or without cardiac defect) were described; growth hormone therapy was used for height gain in Silver-Russell syndrome. Two patients with Holt-Oram syndrome (atrial septal defect and upper limb deformities) survived to ages 11 and 29 years without diagnosis until cardiac surgery was needed.
What is still missing are prospective studies that stratify patients by the specific genetic variant (FBN1, BMP2, DVL1, or others) rather than by syndromic label alone, and trials that test whether growth hormone or other interventions alter outcomes in these molecularly defined subgroups. Funding for long-term natural history registries and for functional studies of the implicated genes in cardiac and skeletal development is 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.
American journal of diseases of children · 1969 · 96 citations
Frontometaphyseal Dysplasia
AbstractTHIS REPORT was prompted by the discovery of a patient with an unknown osseous dysplasia. We have chosen the namefrontometaphyseal dysplasiato designate this new syndrome of multiple bony defects which is apparently distinct from Pyle's disease, craniometaphyseal dysplasia, craniodiaphyseal dysplasia, and osteopetrosis. Report of a Case A 19-year-old white male patient was admitted for cardiac evaluation (Fig 1). On admission, he was noted to have multiple skeletal anomalies. The patient's father, mother, sister, and two brothers were normal. Consanguinity was denied. The patient was known to have a heart murmur since birth. Five years before admission, increased fatigability and exertional dyspnea were noted. Past history indicated that the patient had a 50% to 60% hearing loss bilaterally. Physical examination revealed a well-nourished boy with a marked supraorbital ridge, slight facial asymmetry, wide nasal bridge, mild antimongoloid obliquity, hirsutism above the eyebrows, and a small pointed chin (Fig 2).
American Journal of Medical Genetics · 1996 · 15 citations
The Floating Harbor syndrome with cardiac septal defect
AbstractThe Floating Harbor syndrome of short stature, very delayed bone age, expressive language delay, and characteristic facial changes has not been associated with cardiac anomalies, except for one patient with pulmonic stenosis. We report on a 10-year-old boy with the syndrome and tetralogy of Fallot with atrial septal defect.
Case Reports in Endocrinology · 2018 · 14 citations · open access
The Clinical Cases of Geleophysic Dysplasia: One Gene, Different Phenotypes
AbstractBackground . Geleophysic dysplasia is a rare multisystem disorder that principally affects the bones, joints, heart, and skin. This condition is inherited either in an autosomal dominant pattern due to FBN1 mutations or in an autosomal recessive pattern due to ADAMTSL2 mutations . Two patients with unaffected parents from unrelated families presented to their endocrinologist with severe short stature, resistant to growth hormone treatment. Routine endocrine tests did not reveal an underlying etiology. Exome sequencing was performed in each family. Our two patients, harboring de novo heterozygous FBN1 mutations p.Tyr1696Asp and p.Cys1748Ser, had common clinical symptoms such as severe short stature, characteristic facial features, short hands and feet, and limitation of joint movement. However, one patient had severe cardiac involvement whereas the other patient had tracheal stenosis requiring tracheostomy placement. Conclusions . Patients with severe dwarfism, skeletal anomalies, and other specific syndromic features (e.g., tracheal stenosis and cardiac valvulopathy) should undergo genetic testing to exclude acromelic dysplasia syndromes.
Molecular Syndromology · 2020 · 12 citations · open access
Robinow Syndrome and Brachydactyly: An Interplay of High-Throughput Sequencing and Deep Phenotyping in a Kindred
AbstractWe report a family with a spectrum of short stature, craniofacial dysmorphism, and digital anomalies in a father and 2 daughters, with the youngest (proband) displaying a severe phenotype. Clinically, autosomal dominant Robinow syndrome (ADRS) was diagnosed. Whole-exome sequencing identified a heterozygous pathogenic BMP2 variant in the father and his daughters. The phenotype of short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies related to BMP2 haploinsufficiency has some facial and digital resemblance to ADRS. Although this variant segregated in the affected members, it failed to explain the severe phenotype of the proband. A reanalysis of the girl's raw data confirmed 2 disorders: a de novo likely pathogenic DVL1 variant implicated in ADRS and the familial BMP2 variant. A close interplay of high-throughput sequencing and deep phenotyping unraveled the complexities of the blended phenotype in the proband.
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.
International Journal of Medicine and Surgery · 2015 · 0 citations · open access
Holt-Oram syndrome: a simple diagnosis that is often delayed
AbstractBackground: Holt-Oram syndrome is uncommon. It is characterized by heart disease and skeletal abnormalities of the hands and arms (upper limbs). This conditionis inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The most common problem is an atrial septal defect, and upper limb musculoskeletal deformities. These morphological characteristics should suggest a cardiac abnormality which is usually silent. Cases presentation: We report isolated cases with this syndrome. Tow patients with skeletal anomalies have been survived 11 and 29 years with their congenital cardiac defects without being diagnosed in despite of their obvious upper limbs deformities. In the two cases, the diagnosis of Holt-Oram syndrome was delayed and the cardiac defects have been revealed at the stage of surgery. We will discuss the variables of the musculoskeletal abnormalities and their association with the cardiac morphological defects. Conclusion: Holt-Oram syndrome is a rare inherited clinical disorder. Cardiac defect should be suspected in the presence of congenital upper limb abnormalities.
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.
