DeCure for Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for neurodevelopmental disorder with dysmorphic facies and distal limb anomalies — screening already-approved drugs against its 10-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 distal limb anomalies maps to a 10-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 distal limb 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
SET domain containing 1A, histone lysine methyltransferase (SETD1A) — SETD1A 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3S8S · 1.3 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
Four children with severe learning disability, motor delay, hypotonia, delayed visual maturation, postural asymmetry and epilepsy were found to have a submicroscopic deletion of chromosome 1p36.3 after conventional cytogenetic examination had been normal. Their physical features included body asymmetry, microcephaly, deep-set eyes, sharply defined eye sockets and mid-face hypoplasia. No drug or treatment was studied.
Twenty-five novel individuals with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) caused by 20 distinct heterozygous variants in the BPTF gene were described, bringing the total reported cases to 36. In addition to the previously known developmental delay, intellectual disability, speech delay, postnatal microcephaly and dysmorphic features, this cohort showed mild brain abnormalities, seizures, scoliosis and a variety of ophthalmologic complications. Four of the 25 individuals had inherited BPTF changes. No drug or treatment was studied.
Three cases from one family carried a homozygous likely pathogenic variant in the POP1 gene, which is usually associated with anauxetic dysplasia, a skeletal condition with normal neurodevelopment. The proband had global developmental delay, autism, microcephaly, dysmorphic features and multiple congenital anomalies. Two subsequent pregnancies were terminated because of multiple congenital malformations; fetal DNA showed the same homozygous POP1 variant. Expression of RMRP was reduced in the proband compared with control and slightly reduced in both heterozygous parents. No drug or treatment was studied.
No clinical trial, no drug intervention, no survival or response rate data exist for any of these genetic neurodevelopmental disorders. What is missing is any attempt to repurpose an existing drug, any preclinical model work testing a compound, any patient stratification beyond genetic diagnosis, and any funding for a treatment trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Developmental Medicine & Child Neurology · 2000 · 32 citations
Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3
AbstractWe describe four children with dysmorphic syndrome with severe learning disability (SLD). Their chromosomes had been normal on conventional cytogenetic examination. However, screening using a multiprobe fluorescence in situ hybridisation (FISH) technique for subtelomeric abnormalities revealed a deletion of the p arm of chromosome 1. The physical features include body asymmetry, microcephaly, distinctive facies with deep-set eyes, sharply defined eye sockets, and mid-face hypoplasia; the neurodevelopmental profile was characterised by SLD, motor delay with hypotonia, markedly delayed visual maturation, and postural asymmetry together with epilepsy. This phenotype is consistent with that described for partial monosomy for 1p36.3.
American Journal of Medical Genetics Part A · 2021 · 28 citations · open access
Phenotypic expansion of the <scp><i>BPTF</i></scp>‐related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
AbstractNeurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.
Developmental Medicine & Child Neurology · 2000 · 13 citations
Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3
AbstractWe describe four children with dysmorphic syndrome with severe learning disability (SLD). Their chromosomes had been normal on conventional cytogenetic examination. However, screening using a multiprobe fluorescence in situ hybridisation (FISH) technique for subtelomeric abnormalities revealed a deletion of the p arm of chromosome 1. The physical features include body asymmetry, microcephaly, distinctive facies with deep‐set eyes, sharply defined eye sockets, and mid‐face hypoplasia; the neurodevelopmental profile was characterised by SLD, motor delay with hypotonia, markedly delayed visual maturation, and postural asymmetry together with epilepsy. This phenotype is consistent with that described for partial monosomy for 1p36.3.
Clinical Genetics · 2024 · 2 citations · open access
Novel phenotype associated with homozygous likely pathogenic variant in the <scp>POP1</scp> gene
AbstractThe biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies. Two subsequent pregnancies were terminated due to multiple congenital malformations. Fetal DNA samples revealed the same homozygous variant in the POP1 gene. Expression of the RMRP was reduced in the proband compared with control and slightly reduced in both heterozygous parents, carriers for this variant. To our knowledge, this is the first report of this new phenotype, associated with a novel likely pathogenic variant in POP1. Our findings expand the phenotypic spectrum of POP1-related disorders.
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.
