DeCure for Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability — 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 moduleMicrocephaly with or without chorioretinopathy, lymphedema, or intellectual disability 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 microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability 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
kinesin family member 11 (KIF11) — KIF11 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3HQD · 2.19 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (MCLMR) is caused by heterozygous mutations in KIF11, a gene encoding a spindle motor protein. A 2025 systematic review of published MCLMR cases identified 55 pathogenic KIF11 variants distributed throughout the gene, with a recurrent mutational hotspot at c.1159 C>T (p.Arg238*). Frameshift and splicing variants together account for over 50% of cases. Missense variants are associated with more severe phenotypic manifestations, suggesting a genotype-phenotype correlation. A 2022 report described a 3-year-old girl with a novel de novo KIF11 duplication variant (c.2409dupA, p.Leu804ThrfsTer13) who had isolated microcephaly and normal motor development, demonstrating that KIF11 mutation can present without the full syndrome.
The hallmark features—microcephaly, chorioretinopathy, and lymphedema—are frequently recognised at birth, but chorioretinopathy may develop later. A 1999 family study recommended fundoscopic examination in all patients with microcephaly with or without lymphedema. A 2014 report of five individuals with de novo novel KIF11 mutations described severe microcephaly, marked simplification of the gyral pattern on neuroimaging, bilateral chorioretinopathy, and developmental delay; three had congenital lymphedema, and one had congenital bilateral sensorineural hearing loss. A 2017 report of two patients added congenital heart defects and, in one case, lissencephaly as rare associated findings. A 2025 case report described an 8-year-old boy with microcephaly, characteristic chorioretinopathy, mild developmental delay, special facial features, bilateral simian crease, and metabolic abnormalities including elevated urine glucose and ketone bodies despite normoglycemia; brain MRI showed simplified gyration, delayed myelination, and cortical thickening.
The clinical spectrum is wide, ranging from isolated microcephaly to the full triad plus intellectual disability, heart defects, hearing loss, and metabolic anomalies. No treatment is described in any of these reports. What remains missing are prospective natural history studies with standardised phenotyping, larger cohorts to validate the proposed genotype-phenotype correlations, and any preclinical or clinical work aimed at therapeutic 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.
American Journal of Medical Genetics Part A · 2014 · 55 citations
Congenital microcephaly and chorioretinopathy due to de novo heterozygous <i>KIF11</i> mutations: Five novel mutations and review of the literature
AbstractThe microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a distinct microcephaly syndrome. The hallmark features, microcephaly, chorioretinopathy, and lymphedema are frequently recognized at birth. Another clinical entity, the chorioretinal dysplasia, microcephaly and mental retardation syndrome (CDMMR) is a highly overlapping syndrome characterized by more variable lymphedema. Recently, heterozygous mutations in KIF11, a gene encoding a critical spindle motor protein of the Kinesin family, have been reported in individuals with MLCRD, and in individuals with CDMMR. This finding is suggestive of a single clinically variable spectrum. Here, we report on de novo novel mutations of KIF11 in five individuals with severe microcephaly, marked simplification of the gyral pattern on neuroimaging, bilateral chorioretinopathy, and developmental delay. Three patients had congenital lymphedema, and one had congenital bilateral sensorineural hearing loss. This report, therefore, further expands the clinical and molecular spectrum of KIF11-associated microcephaly.
American Journal of Medical Genetics · 1999 · 31 citations
Microcephaly-lymphedema-chorioretinal dysplasia: A unique genetic syndrome with variable expression and possible characteristic facial appearance
AbstractWe report on a follow-up examination of a family with microcephaly and lymphedema. The finding of chorioretinal dysplasia with variable visual deficit in multiple relatives, which was not previously discovered, supports the concept of microcephaly, lymphedema, and chorioretinopathy as being a single autosomal dominant genetic entity with variable expression. We recommend that fundoscopic examination be performed in all patients with microcephaly with or without lymphedema.
International Journal of Clinical Pediatrics · 2017 · 1 citations · open access
Microcephaly-Lymphedema-Chorioretinal Dysplasia Syndrome: Two Case Reports
AbstractMicrocephaly-lymphedema-chorioretinal dysplasia is a rare syndrome in which the component of chorioretinopathy may develop later. We describe two patients with microcephaly-lymphedema-chorioretinal dysplasia syndrome who had characteristic facial features and congenital heart defects. Second patient had also lissencephaly which was very rarely reported before. Int J Clin Pediatr. 2017;6(3-4):42-45 doi: https://doi.org/10.14740/ijcp275w
Journal of Head & Neck Physicians and Surgeons · 2022 · 1 citations · open access
Identification of a Novel KIF11 Variant p.(Leu804Thrfs Ter13) in a Case with Isolated Microcephaly
AbstractMicrocephaly is a rare neurological condition, and it is characterized by a smaller head than other children of the same age and sex. Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MLCRD) is a syndrome with a varying spectrum that occurs as a result of variants of KIF11 gene. A 3-year-old girl was presented to our clinic with microcephaly; she had no motor or growth retardation except microcephaly. After obtaining a normal karyotype and microarray result, Trusight One-Expanded Panel analysis showed NM_004523.4 ( KIF11 ): c. 2409dupA (p. Leu804Thrfs Ter13) heterozygous pathogenic novel variant. Patients who have KIF11 mutation often also have different clinical features; in our case, the motor development is consistent with its peers and has a history of prenatal and postnatal microcephaly. Microcephaly can be caused by a variety of genetic mutations. In our case, firstly we identify the association of a novel de novo KIF11 gene duplication variant related to isolated microcephaly.
BMC Ophthalmology · 2025 · 0 citations · open access
Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation associated with KIF11 pathogenic variant: case report and genotype-phenotype correlation analysis
AbstractBACKGROUND: Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) is a rare autosomal dominant disease caused by variants in the KIF11 gene. Additionally, recent advances in genetic testing have led to the increasing identification of KIF11 gene variants in FEVR patients. Harboring similar point variants in the KIF11 gene, patients exhibit striking variability in clinical manifestations. However, comprehensive clinical characterization of MCLMR patients with KIF11 variants are only mentioned by a few case reports and the genotypic and phenotypic variability in KIF11-associated disease was not thoroughly investigated. Therefore, one case is discussed alongside a systematic review of published MCLMR cases to clarify genotype-phenotype correlations. CASE PRESENTATION: An 8-year-old boy was referred to our clinic due to poor vision. Clinical evaluation revealed microcephaly, characteristic chorioretinopathy and mild developmental delay, in the absence of primary lymphedema. Additional findings included special facial features, bilateral simian crease and metabolic abnormalities featuring elevated urine glucose and ketone bodies despite normoglycemia. Brain magnetic resonance imaging (MRI) demonstrated microcephaly with simplified gyration, delayed myelination, and cortical thickening. Whole exome sequencing (WES) identified a previously reported synonymous variant in KIF11 (c.2922G > A, p.Pro974=), which was confirmed and co-segregated by Sanger sequencing. CONCLUSIONS: A Chinese boy was diagnosed with MCLMR following the identification of a pathogenic KIF11 gene point variant, as classified according to ACMG guidelines. Combined with previously reported literature, a total of 55 pathogenic KIF11 variants have been identified, distributed throughout the entire gene. A recurrent mutational hotspot (c.1159 C > T, p.Arg238*) was observed. Additionally, frameshift and splicing variants collectively account for over 50% of cases. Notably, missense variants are associated with more severe phenotypic manifestations, suggesting a genotype-phenotype correlation. This case, supported by comprehensive clinical data, contributes to a more complete elucidation of the phenotypic spectrum of KIF11-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.
