DeCure for Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for congenital heart defects, dysmorphic facial features, and intellectual developmental disorder — 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 moduleCongenital heart defects, dysmorphic facial features, and intellectual developmental disorder 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 congenital heart defects, dysmorphic facial features, and intellectual developmental disorder 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
cyclin dependent kinase 13 (CDK13) — CDK13 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5EFQ · 2.0 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Children with any type of congenital heart defect are at roughly double the risk of a developmental disability compared to children without major birth defects (relative risk 2.08, 95% CI 2.03–2.14, based on a population-level sample of nearly two million children). The elevated risk applies to critical and non-critical CHD alike, and includes intellectual disability, language impairment, and autism spectrum disorder in the atrial septal defect group. About 30% of newborns with CHD have an identifiable genetic syndrome, and in the neonatal period the dysmorphic features that might suggest a monogenic cause — ocular, ear, mouth, palate, and phalangeal anomalies — overlap heavily with those seen in genomic rearrangement syndromes, making early diagnosis difficult without molecular testing.
A 2016 exome-sequencing study of over 1,200 CHD family trios found that roughly 20% of children with severe CHD who also had neurodevelopmental disorders and other extracardiac anomalies carried an excess of harmful de novo mutations. Only 2% of children with isolated CHD had such an excess. The same study identified 85 mutations shared between children with CHD and children with neurodevelopmental disorders but no heart problems — more than double the number expected by chance. These mutations are not inherited but arise spontaneously during fetal development, and the finding suggests a common genetic origin for some heart and brain abnormalities.
A 2025 case report describes a 5.9-year-old boy with growth retardation, intellectual disability, ventricular and atrial septal defects, patent ductus arteriosus, scoliosis, finger contractures, and dysgenesis of the corpus callosum. He carried a de novo missense mutation (c.898C>G, p.Gln300Glu) in the ABL1 gene, expanding the known genetic spectrum of congenital heart defects and skeletal malformations syndrome. A separate 2022 case report describes Cayler cardio-facial syndrome, characterised by asymmetric crying facies and congenital heart defects, in a four-year-old boy. Both reports are single cases and do not provide data on treatment or outcomes beyond the description of the phenotype.
What is still missing is a prospective trial that tests whether early genetic screening in newborns with CHD leads to earlier developmental interventions and measurable improvements in cognitive or motor outcomes. The population-level data show increased risk but do not tell us which children will benefit from which intervention, and the genetic studies have not yet been translated into a validated clinical test that alters management. Funding for such a trial, and for the development of a reliable polygenic or mutation-specific risk score, remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Birth Defects Research · 2023 · 7 citations · open access
Elevated risk for developmental disabilities in children with congenital heart defects
AbstractBACKGROUND: This study examined risk for developmental disabilities in preschool-aged children with a congenital heart defect (CHD) at the population level. METHODS: Statewide birth, birth defects, and preschool developmental disability records were integrated. The final sample included 1,966,585 children (51.0% male). Children were grouped by type(s) of CHD: critical CHD, noncritical CHD, atrial septal defect, or no major birth defects (groups were mutually exclusive). RESULTS: Children with a CHD (any type) were at increased risk for developmental disability (any type) (RR 2.08, 95% CI 2.03-2.14, P < .001). Children in the critical CHD, noncritical CHD, and atrial septal defect groups were at increased risk for developmental delay, intellectual disability, language impairment, other health impairment, and any disability. Children in the atrial septal defect group were at increased risk for autism spectrum disorder and speech impairment. For all CHD groups, risk was greatest for other health impairment and intellectual disability. CONCLUSIONS: Increased risk for developmental disabilities was identified for children with less severe CHDs as well as for children with more severe (critical) CHDs. All children with CHDs should be closely monitored so that appropriate interventions can be initiated as early as possible to maximize learning outcomes.
Journal of Pediatric Genetics · 2021 · 5 citations · open access
Monogenic Syndromes with Congenital Heart Diseases in Newborns (Diagnostic Clues for Neonatologists): A Critical Analysis with Systematic Literature Review
AbstractCongenital heart disease (CHD), the most common major congenital anomaly, is associated with a genetic syndrome (chromosomal anomalies, genomic disorders, or monogenic disease) in 30% of patients. The aim of this systematic review was to evaluate if, in the neonatal setting, clinical clues that orient the diagnostic path can be identified. For this purpose, we revised the most frequent dysmorphic features described in newborns with CHD, comparing those associated with monogenic syndromes (MSG) with the ones reported in newborns with genomic disorders. For this systematic review according to PRISMA statement, we used PubMed, Medline, Google Scholar, Scopus database, and search terms related to CHD and syndrome. We found a wide range of dysmorphisms (ocular region, ears, mouth, and/or palate and phalangeal anomalies) detected in more than half of MSGs were found to be associated with CHDs, but those anomalies are also described in genomic rearrangements syndromes with equal prevalence. These findings confirmed that etiological diagnosis in newborns is challenging, and only the prompt and expert recognition of features suggestive of genetic conditions can improve the selection of appropriate, cost-effective diagnostic tests. However, in general practice, it is crucial to recognize clues that can suggest the presence of a genetic syndrome, and neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate.
American Journal of Medical Genetics Part A · 2025 · 1 citations
A Novel Missense Mutation of the <scp><i>ABL1</i></scp> Gene in a Child With Congenital Heart Defects and Skeletal Malformations Syndrome
AbstractCongenital heart defects and skeletal malformations syndrome (CHDSKM) is a rare autosomal dominant genetic disorder characterized by specific clinical features, including dysmorphic facial traits, congenital heart defects, skeletal abnormalities, joint issues, and failure to thrive. The novelty of this case lies in the identification of a novel mutation in the ABL1 gene, expanding the genetic spectrum associated with this syndrome. A 5.9-year-old boy was referred to the clinic due to growth retardation and intellectual disability. Clinical evaluation revealed several hallmark features of CHDSKM, including distinct facial dysmorphisms such as a broad forehead, frontal bossing, micrognathia, low-set ears, and short palpebral fissures. The patient was diagnosed with congenital heart defects, including a ventricular septal defect, atrial septal defect, and patent ductus arteriosus. Skeletal malformations included scoliosis and finger contractures. Additionally, he exhibited developmental delay, gastrointestinal issues such as umbilical hernia and intestinal malrotation, intellectual disability, and dysgenesis of the corpus callosum, which are atypical for this syndrome. Molecular genetic analysis identified a de novo mutation (c.898C>G) in exon 5 of the ABL1 gene, resulting in a novel missense mutation (p.Gln300Glu). This case emphasizes the importance of considering CHDSKM in the differential diagnosis of children with growth and developmental concerns. The identification of a novel mutation in the ABL1 gene highlights the critical role of early molecular genetic testing, which can facilitate improved management and support for affected individuals and their families.
Acquired Mutations Link Congenital Heart Disease, Neurodevelopmental Disorders
AbstractBack to table of contents Previous article Next article Clinical and Research NewsFull AccessAcquired Mutations Link Congenital Heart Disease, Neurodevelopmental DisordersNick ZagorskiNick ZagorskiPublished Online:4 Feb 2016https://doi.org/10.1176/appi.pn.2016.1b16AbstractAbout 20 percent of children with severe congenital heart disease have an excess of mutations that are also commonly found in children with developmental problems such as autism.A study published December 4 in Science suggests that neurodevelopmental abnormalities in children with congenital heart disease may arise from the acquisition of harmful de novo gene mutations. These are not inherited but rather spontaneously occur during fetal development. These abnormalities include cognitive, motor, social, and language impairments.Michelle Massi"Finding this strong association between the developing heart and brain was a bit surprising, for while the heart and brain are both complex organs, they do separate early in the development process," said study coauthor Jonathan Kaltman, M.D., who is the administrator of the National Heart, Lung, and Blood Institute's (NHLBI) Bench to Bassinet Program, which funded this study."At the same time, it makes sense clinically, given that there are several inherited disorders such as Down's syndrome or DiGeorge syndrome, which feature both cardiac and neurological problems."Investigators from the NHLBI's Pediatric Cardiac Genomics Consortium used a technique known as exome sequencing to scan all the protein-encoding regions of the genome in over 1,200 affected family trios (a child with congenital heart disease [CHD] and his or her parents) along with 900 control trios without CHD.They uncovered almost 400 potentially harmful de novo mutations that significantly contribute to the risk of co-occurring CHD and neurodevelopmental disorders.While an excess number of these harmful mutations were found in only 2 percent of patients who had isolated CHD, the prevalence rose in children with more complications. The mutations were present in about 10 percent of patients who also had neurodevelopmental disorders or other extracardiac congenital anomalies (such as limb or kidney defects), and 20 percent of patients who had both.When the researchers compared the genetic data from children with CHD and children with neurodevelopmental disorders but no heart problems, they found 85 mutations were present in both groups—more than twice as many as would be expected by random chance."These findings show enough statistical risk of developing neurodevelopmental disabilities when these particular gene mutations are present that we might consider developing a genetic test for patients with CHD," Kaltman told Psychiatric News. Such a test could help to identify high-risk children for early interventions that might help to limit developmental delays and improve functioning, he said.In addition to the NHLBI, this study was supported in part by the National Human Genome Research Institute, the Howard Hughes Medical Institute, and Simons Foundation for Autism Research. ■An abstract of "De Novo Mutations in Congenital Heart Disease With Neurodevelopmental and Other Congenital Anomalies" can be accessed here. ISSUES NewArchived
Scholars Journal of Medical Case Reports · 2022 · 0 citations · open access
Cayler Cardio-Facial Syndrome: A Rare Case Report
AbstractBackground: Cayler cardio-facial syndrome is a rare syndrome characterised by asymmetric crying facies with congenital heart defects. Syndrome may be associated with other dysmorphic features and systemic anomalies. Case Report: We report the clinical observation of a 04 years old boy presenting with Cayler cardio-facial syndrome.
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.
