DeCure for Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies — 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 moduleCardiac malformation, cleft lip/palate, microcephaly, and digital anomalies 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 cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies 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
Meis homeobox 2 (MEIS2) — MEIS2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3K2A · 1.95 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Among 191 patients with facial clefts studied in 1970, two-thirds of the 32 deceased children had severe heart disease. In the 150 living patients the incidence of cardiac malformations was 1.3%. Transposition of the great vessels and single ventricle were absent, possibly because the embryological defect for those lesions precedes palatal development by 1.5 to 2 weeks. Heart disease occurred in 20% of children dying with Pierre Robin syndrome but in 75% of deceased infants who had cleft palate without Pierre Robin syndrome.
A 1990 report on 78 patients with clefts and heart disease found that bilateral cleft lip and palate was much more common in those with heart lesions than in cleft patients with normal hearts. Cardiac defects were predominantly conotruncal: tetralogy of Fallot in 24%, with high rates of transposition, atrioventricular septal defect, and truncus arteriosus. Patients with conotruncal defects more often had unilateral or bilateral cleft lip and palate. Additional abnormalities in other systems were present in 87% of patients.
A retrospective evaluation of 1134 cleft patients from 2013 to 2016 found that 178 (15.6%) had cardiac anomalies, 57.3% male and 42.7% female. Cardiac anomalies were most often associated with combined cleft lip and palate (56.1% of the 178). Among cleft types, isolated cleft palate had the highest rate of syndromic association (28.9%). 41.6% of patients with cardiac anomalies had multiple cardiac defects. The most common anomaly was atrial septal defect, seen in 47.8%. A smaller cross-sectional study of 73 children aged 3 to 10 years found 13.7% had congenital cardiac anomalies: atrial septal defect 6.8%, ventricular septal defect 4.1%, and mitral regurgitation 2.7%. ASD was exclusive to males, VSD more common in females, and no significant association was found between cardiac anomalies and cleft type or socioeconomic status.
A Portuguese study of 588 patients from 1992 to 2018 reported 77 (13%) with cardiac anomalies, 53% male, 17% with affected relatives. Isolated cleft palate was the most common cleft type among those with cardiac anomalies (56%). Additional congenital anomalies were found in 89.7%, and a recognisable syndrome in 61.5%, most often Pierre Robin (n=22) then 22q11.2 microdeletion (n=9). The main cardiac anomalies were left-to-right shunts (n=47) and right ventricular outflow tract obstruction (n=14); 26 had ventricular septal defect, 15 atrial septal defect, and seven tetralogy of Fallot. Five patients had dysrhythmias. A Nigerian review of 93 cases found associated anomalies in 15%, with cardiac anomalies in all groups but mostly septal defects compatible with surgery; late detection of cardiac anomalies occurred in three cases. What remains missing is prospective, standardised echocardiographic screening across diverse populations, larger sample sizes to stratify by cleft type and syndrome, and funding for multicentre registries that can link cardiac findings to surgical timing and long-term outcomes.
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 · 1970 · 48 citations
Cardiac Malformations With Facial Clefts
AbstractAmong 191 patients with facial clefts (cleft lip and/or cleft palate), the incidence of congenital heart defects was increased. Two-thirds (21 of 32) of the dead children had severe heart disease. In 150 living patients with facial clefts, the incidence of congenital cardiac malformations was 1.3%. In the 31 patients concordant for facial clefts and heart disease, transposition of the great vessels and single ventricle were unexpectedly absent, probably because the embryological defect responsible for these two cardiac lesions precedes palatal development by 1½ to 2 weeks. The incidence of heart disease, while high (20%) in children dying with the Pierre Robin syndrome, was greater (75%) in deceased infants who had cleft palate without the Pierre Robin syndrome.
Detection of a 22q11.2 Deletion in Cardiac Patients Suggests a Risk for Velopharyngeal Incompetence
AbstractOBJECTIVE: Conotruncal cardiac anomalies frequently occur in patients with DiGeorge or velocardiofacial syndrome. Additionally, these patients may have overt or submucousal cleft palate, as well as velopharyngeal incompetence (VPI). Previous studies have demonstrated that the majority of these patients have a submicroscopic deletion of chromosome 22q11.2. We hypothesized that a subpopulation of newborns and children with congenital heart defects caused by a 22q11.2 deletion are at a high risk for having unrecognized palatal abnormalities. Therefore, we proposed to evaluate a cohort of patients with conotruncal cardiac malformations associated with a 22q11.2 deletion to determine the frequency of palatal abnormalities. METHODS: We identified 14 deletion-positive patients with congenital cardiac defects who had no overt cleft palate. Of the 14 patients evaluated for the 22q11.2 deletion, 8 patients were recruited from a previous study looking for deletions among patients with isolated conotruncal cardiac anomalies. Informed consent was obtained in these cases. The remaining patients had the deletion study on a clinical basis, ie, conotruncal cardiac defect and an absent thymus, immunodeficiency, or minor dysmorphia appreciated by the clinical geneticist. These patients were evaluated by a plastic surgeon and speech pathologist looking for more subtle palatal anomalies such as a submucousal cleft palate, absence of the musculous uvuli, and VPI. Some patients underwent videofluoroscopy or nasendoscopy depending on their degree of symptoms and age. VPI was not ruled out until objective evaluation by a speech pathologist and plastic surgeon was obtained. In addition, the child had to be old enough to provide an adequate speech sample. RESULTS: Of the 14 patients evaluated, 6 patients older than 1 year were found to have VPI. It is noteworthy that 3 of these patients were older than 5 years and had remained unrecognized until this study. The remaining 6 patients had inconclusive studies based on their age (younger than 26 months) and their inability to participate in adequate speech evaluations. Two of these patients, however, had histories of nasal regurgitation suggesting VPI and, in addition, had incomplete closure of the velopharyngeal mechanism during crying and swallowing observed during nasendoscopic examination-consistent with the diagnosis of VPI. Thus, 8 of 14 patients evaluated had evidence of VPI by history and examination. The remaining 6 patients will require further study when they are older before a definitive palatal diagnosis can be made. CONCLUSIONS: A significant number of patients with a 22q11.2 deletion in a cardiac clinic may have unrecognized palatal problems. Recognition of such abnormalities will afford patients the opportunity for intervention as needed, ie, speech therapy and/or surgical intervention. Notably, two of our patients with findings suggesting VPI were infants and will, therefore, be afforded the opportunity for close follow-up and early intervention. Furthermore, three school-aged children had palatal abnormalities that were unrecognized until this study. Thus, we recommend 22q11.2 deletion studies in patients with conotruncal cardiac malformations, followed by extensive palatal and speech evaluations when a deletion is present.
The Cleft Palate-Craniofacial Journal · 1990 · 27 citations
Congenital Heart Anomalies in Patients with Clefts of the Lip and/or Palate
AbstractThe nature and severity of congenital heart disease in 78 patients who presented with clefts of the lip and/or palate is reported. The prevalence of bilateral cleft lip and palate in patients with heart lesions was much higher than in cleft patients with normal hearts. Cardiac defects were predominantly conotruncal. Tetralogy of Fallot was present in 24 percent of patients; the prevalence of transposition, atrioventricular septal defect, and truncus arteriosus was also disproportionately high. Patients with conotruncal defects had a greater prevalence of either unilateral or bilateral cleft lip and palate. Most patients with congenital heart disease and clefting had additional abnormalities. Anomalies of other systems were found to be present in 87 percent of patients.
Congenital Cardiac Tumors in Association with Orofacial Clefts
AbstractThe case of an infant with a complete cleft of the primary and secondary palate (class III) and right unilateral complete cleft lip who demonstrated failure to thrive due to a primary congenital cardiac fibroma is described. This tumor required cardiac transplantation for effective treatment. A review of the literature, although replete with associations of cleft lip/palate and congenital heart disease, does not reveal a congenital cardiac tumor/orofacial cleft association or syndrome. Failure to thrive, however, which is common in such infants, may well be associated with congenital cardiac anomalies and should be carefully ruled out. Treatment of cardiac fibromas is discussed along with the usefulness of two-dimensional echocardiography and the importance of the team approach in the management of these infants.
Turkish Journal of Plastic Surgery / Türk Plastik Rekonstrüktif ve Estetik Cerrahi Dergisi · 2017 · 1 citations
Evaluation of the Variety and Incidence of Cardiac Anomalies Associated with Cleft Lip and Palate: A Retrospective Evaluation of 1134 Patients
AbstractObjective: To perform a retrospective analysis of patients with cleft lip and palate admitted to the Hacettepe University Department of Plastic Reconstructive and Aesthetic Surgery in the years 2013–2016, and to determine the overall prevalence and variety of associated congenital cardiac anomalies. Materials and Methods: Demographic variables of 1134 cleft patients admitted between July 1, 2013 and April 15, 2016 were retrospectively evaluated. Gender, cleft type, associated syndromes, type of associated congenital cardiac anomaly were recorded. Results: Of the 1134 patients, 178 (15.6%) had cardiac anomalies, of which 102 patients (57.3%) were male and 76 (42.7%) were female. Congenital cardiac anomalies were mostly associated with concomitant presentation of cleft lip and palate at a rate of 56.1% (100/178 patients). Among the patients with various cleft types, 28.9% with isolated cleft palate had the highest rate of syndromic association, and 74 (41.6%) had multiple cardiac anomalies. The most common cardiac anomaly was atrial septal defect, seen in 47.8% of the patients. Conclusion: As cleft lip and palate are one of the most common congenital anomalies worldwide, associated cardiac anomalies are healthcare problems that require attention.
Anomalies associated with cleft lip and palate in patients seen at the National Orthopaedic Hospital, Enugu
AbstractBackground: Cleft deformities of the face are one of the major congenital anomalies seen in our environment. No information is available in this centre on the incidence of the deformities and associated anomalies which influence management and outcomes. This paper hopes to contribute to this. Materials and methods The records of all patients with cleft lip and palate seen in the National Orthopaedic Hospital, Enugu from January 1993 to December 1999 were reviewed retrospectively. Results: There were 93 cases. Fourteen were isolated cleft palate; 37, isolated cleft lip and 42 were combined cleft lip and palate. There were associated anomalies in 15%. These occurred most commonly in isolated cleft palate and combined cleft lip and palate patients and least among the isolated cleft lip patients. Multiple anomalies were present in all groups but commonest in combined lip and palate patients. Cardiac anomalies were noted in all groups. Late diagnosis of associated cardiac anomalies was noted in three cases. When characterized they were mostly septal defects compatible with surgery. Late detection was noted in some cardiac anomalies. Conclusion: Routine paediatric evaluation of all cleft patients and the establishment of cleft centres are advocated. Keywords: cleft lip and palate, associated anomaly. Nigerian Journal of Plastic Surgery Vol. 3 (2) 2007: pp. 31-35
Biological and Clinical Sciences Research Journal · 2024 · 1 citations · open access
FREQUENCY OF CARDIAC ANOMALIES IN PATIENTS WITH CLEFT LIP AND PALATE PRESENTED AT HAYATABAD MEDICAL COMPLEX
AbstractCleft lip and/or palate are among the most common congenital craniofacial anomalies and are often associated with other systemic anomalies, including congenital cardiac anomalies (CCAs). The identification of CCAs in these patients is crucial for optimizing surgical outcomes and long-term health. Objective: To determine the frequency and types of congenital cardiac anomalies (CCAs) in patients with cleft lip and/or palate. Methods: This cross-sectional study was conducted at the burns and plastic surgery unit, Hayatabad Medical Complex, Peshawar. Children aged 3 to 10 years with cleft lip, cleft palate, or both were included. All patients underwent a detailed echocardiographic evaluation to identify CCAs, which were categorized as Atrial septal defect (ASD), Ventricular septal defect (VSD) and Mitral regurgitation. Results: Out of 73 patients included, 13.7% were found to have CCAs. The most common anomalies were atrial septal defect (6.8%), ventricular septal defect (4.1%), and mitral regurgitation (2.7%). ASD was observed exclusively in males, while VSD was more common in females. The younger age group (3–6 years) showed a higher prevalence of ASD. No significant associations were observed between CCAs and socioeconomic status or cleft type. Conclusion: Congenital cardiac anomalies are prevalent in patients with cleft lip and palate, with atrial septal defect and ventricular septal defect being the most common.
Scientia Medica · 2021 · 0 citations · open access
Orofacial clefts associated with cardiac anomalies
AbstractAIMS: Orofacial clefts (OFC) are a heterogeneous group of birth defects arising in about 1.7/1000 newborns. They can occur with other congenital anomalies, including heart defects. We aim to describe a population with orofacial clefts and associated cardiac anomalies.METHODS: Retrospective study of patients attended in the Cleft Lip and Palate Multidisciplinary Group outpatient clinic at Hospital Universitario São João, Porto-Portugal. Medical records from January 1992 through December 2018 were reviewed. Patients were divided into four groups according to the Spina classification: cleft lip (CL), cleft lip and palate (CLP), isolated cleft palate (CP) and atypical cleft (AC). Further categorization included gender, affected relatives, associated congenital anomalies and syndromes.RESULTS: From the 588 patients included, 77 (13%) presented cardiac anomalies. Of those with orofacial cleft and cardiac anomalies, 53% were males and 17% had known affected relatives. CP was the most common cleft among patients with cardiac anomaly (~56%). Additional congenital anomalies were found in 89.7% of patients, namely facial defects, central nervous system, renal and skeletal malformations. A recognizable syndrome was identified in 61.5%, being Pierre-Robin the most common (n=22), followed by 22q11.2 microdeletion (n=9). Both additional congenital anomalies and recognizable syndromes were significantly more prevalent in patients with heart disease (p<0.05). The main groups of cardiac anomalies were left-to-right shunt (n=47) and right ventricular outflow tract obstruction (n=14). From these, 26 had a ventricular septal defect, 15 atrial septal defect and seven patients had tetralogy of Fallot. Five patients had dysrhythmias.CONCLUSIONS: Due to the high prevalence of cardiac anomalies in the cleft population, a routine cardiac evaluation should be performed in all these patients.
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.
