DeCure for Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for neurodevelopmental disorder with dysmorphic facies and thin corpus callosum — 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 moduleNeurodevelopmental disorder with dysmorphic facies and thin corpus callosum 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 neurodevelopmental disorder with dysmorphic facies and thin corpus callosum 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
In 135 children with structural CNS defects on MRI, agenesis of the corpus callosum was found in 7. All seven had dysmorphic features and psychomotor retardation; six had epileptic seizures, and all had abnormal neurologic examinations. The established causes in four of these children were partial trisomy 13, partial duplication of 10q, Aicardi syndrome, and fetal intracranial bleeding from injury. A fifth child had a coexisting Dandy-Walker malformation, suggesting a genetic cause. In a separate series of 2164 children who underwent CT brain, 22 (1%) had corpus callosum agenesis; 64% were male, most were not syndromic, and about one third had epileptic disorders.
A girl with dysmorphic features, infantile-onset seizures, hypotonia, marked developmental delay, and dysgenesis of the corpus callosum was found to have a de novo 1.47 Mb deletion at 1q44 that included ZNF238 but not CEP170 or AKT3. This provided evidence that haploinsufficiency of ZNF238, not AKT3, is causative of corpus callosum abnormalities in patients with terminal 1q deletions. A 15-year-old boy with neurodevelopmental disorder and brain malformations carried a heterozygous missense variant in NFIB, which he inherited from his substantially healthy mother who had only minor physical and neuroanatomical defects, demonstrating marked intrafamilial variability in NFIB-related developmental disorder.
Two reviews summarise that agenesis of the corpus callosum can occur in isolation or as part of congenital syndromes, and that copy number variations and single gene mutations have been rapidly identified through improved genetic studies, mouse models, and neuroimaging. One review covers callosal involvement in genetic disorders (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams syndrome, fragile X) and prenatal injuries (premature birth, fetal alcohol syndrome), as well as in developmental disorders defined by behaviour (language delay, dyslexia, ADHD, autism, Tourette syndrome). The other provides a classification of clinical and genetic features of syndromes associated with callosal agenesis.
What remains missing is a unified genetic and developmental framework that can guide therapy development for callosal agenesis or related neurodevelopmental disorders. No drug treatment is mentioned in any of these abstracts. The field still lacks prospective trials, patient stratification by molecular subtype, and funding to move from genetic discovery to intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 2014 · 356 citations
Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes
AbstractThe corpus callosum is the largest fibre tract in the brain, connecting the two cerebral hemispheres, and thereby facilitating the integration of motor and sensory information from the two sides of the body as well as influencing higher cognition associated with executive function, social interaction and language. Agenesis of the corpus callosum is a common brain malformation that can occur either in isolation or in association with congenital syndromes. Understanding the causes of this condition will help improve our knowledge of the critical brain developmental mechanisms required for wiring the brain and provide potential avenues for therapies for callosal agenesis or related neurodevelopmental disorders. Improved genetic studies combined with mouse models and neuroimaging have rapidly expanded the diverse collection of copy number variations and single gene mutations associated with callosal agenesis. At the same time, advances in our understanding of the developmental mechanisms involved in corpus callosum formation have provided insights into the possible causes of these disorders. This review provides the first comprehensive classification of the clinical and genetic features of syndromes associated with callosal agenesis, and provides a genetic and developmental framework for the interpretation of future research that will guide the next advances in the field.
Journal of Neurodevelopmental Disorders · 2010 · 265 citations · open access
Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement
AbstractThis review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)-the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome).
Agenesis of Corpus Callosum: Clinical Description and Etiology
AbstractIn 135 children (aged 3 months to 15 years) with structural defects of the central nervous system found on magnetic resonance imaging, agenesis of the corpus callosum was evident in 7. The etiology of agenesis of the corpus callosum has been established in four children: partial trisomy of chromosome 13, partial duplication of the long arm of chromosome 10, Aicardi's syndrome, and intracranial bleeding during the fetal period as a result of injury. Agenesis of the corpus callosum coexisted with a Dandy-Walker malformation in one other patient, which suggests a genetic etiology. In spite of these variable etiologies, dysmorphic features were identified in all seven patients, as was psychomotor retardation. Epileptic seizures had occurred in six patients, and all manifested abnormalities on neurologic examination.
American Journal of Medical Genetics Part A · 2013 · 28 citations
Haploinsufficiency of <i>ZNF238</i> is associated with corpus callosum abnormalities in 1q44 deletions
AbstractA variety of candidate genes have been proposed to cause corpus callosum abnormalities (CCAs) in patients with terminal chromosome 1q deletions. Recent data excluded AKT3 and implicated ZNF238 and/or CEP170 as genes causative of corpus callosum anomalies in patients with 1q43-1q44 deletions. We report on a girl with dysmorphic features, seizures beginning in infancy, hypotonia, marked developmental delay, and dysgenesis of the corpus callosum. Chromosomal microarray analysis detected a de novo 1.47 Mb deletion at 1q44. The deleted interval encompasses the ZNF238 gene but not the CEP170 or AKT3 genes, thus providing additional evidence for the former and against the latter as being causative of corpus callosum anomalies in patients with such deletions.
AbstractOBJECTIVE: The objectives are to analyse corpus callosum agenesis in children with various neurological problems in a hospital set-up, and to study the neurological and systemic abnormalities associated with this condition. METHODS: The children with various neurological problems who underwent computerized tomography brain from January 1993 to December 1997, and were found to have corpus callosum agenesis, formed the subjects of this study. These children were examined for any syndromic association, congenital infections or metabolic defects. RESULTS: Out of 2164 children who underwent computerized tomography brain, 22 had corpus callosum agenesis (1%). Most cases were not syndromic and 64% were males. Epileptic disorders were noted in about one third of cases. CONCLUSION: Corpus callosum agenesis an important anomaly in children with neurodevelopment handicaps, usually detected by neuroradiology.
American Journal of Medical Genetics Part A · 2023 · 3 citations · open access
Marked intrafamilial variability of clinical and neuroimaging manifestations in <i>NFIB</i>‐related developmental disorder
AbstractNFIB belongs to the nuclear factor I (NFI) family of transcription factors that, by activating or repressing gene expression during embryogenesis, has a relevant role in the development of several organs including the brain. Heterozygous pathogenic variants of NFIB have recently been associated with developmental delay and mild-to-moderate intellectual disability, macrocephaly, nonspecific facial dysmorphisms, and corpus callosum dysgenesis. We identified a heterozygous missense variant in the NFIB gene in a 15-year-old boy with neurodevelopmental disorder and brain malformations, who inherited the variant from his substantially healthy mother presenting only minor physical and neuroanatomical defects.
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.
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