DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Malan overgrowth syndrome — 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 moduleMalan overgrowth syndrome 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 malan overgrowth syndrome 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
nuclear factor I X (NFIX) — NFIX 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 9WA7 · 2.31 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Malan syndrome is a rare overgrowth disorder caused by haploinsufficiency of the NFIX gene, located on chromosome 19 at p13.2. The syndrome results from heterozygous loss-of-function mutations, microdeletions, or, as reported in one 2024 case, an intragenic duplication of exons 6 and 7 that also leads to NFIX haploinsufficiency. NFIX encodes a DNA-binding transcription factor in the nuclear factor one family that regulates growth of connective tissues. Malan syndrome is allelic to Marshall-Smith syndrome, but the two are clinically distinct because Marshall-Smith variants cluster between exons 6 and 10 and can escape nonsense-mediated decay, producing a dominant-negative effect and a more severe phenotype. Malan syndrome variants are typically missense changes in exon 2 or protein-truncating variants that trigger nonsense-mediated decay.
The clinical phenotype includes macrocephaly, a long and slender body habitus, skeletal abnormalities, intellectual disability, dysmorphic facial traits, visual problems, and advanced bone age. Overgrowth can be present at birth, especially as large head circumference, and continues after birth, though statural growth velocity decreases with age. A 2024 longitudinal case report covering 15 years of follow-up described a single patient’s presentation, management, and neurocognitive development, noting improvements over time with early intervention and personalised therapeutic strategies. That report did not provide quantitative outcome measures such as survival or response rates, and no controlled treatment data exist.
No drug treatment for Malan syndrome is described in any of these abstracts. The 2016 review of overgrowth in children and adolescents discusses diagnosis and treatment broadly but does not name any specific drug or therapy for Malan syndrome. The 2012 review summarises overgrowth syndromes without mentioning any pharmacological intervention. What is missing is any clinical trial, any tested drug, any quantitative evidence of treatment efficacy, and any patient stratification beyond the single case report. No funding for a drug-repurposing trial in Malan syndrome is mentioned.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Fetal and Pediatric Pathology · 2012 · 5 citations
Commonest Overgrowth Syndromes
AbstractOvergrowth syndromes, although rare, are diagnosed more frequently lately. Major progress, such as the identification of genetic causes, has recently enhanced the delineation of the characteristic and noncharacteristic manifestations, phenotype-genotype correlations and knowledge of the underlying pathophysiologic mechanisms. This review provides a summary of the most important overgrowth syndromes aiming to familiarize the treating physician with the cardinal clinical features involved in these syndromes that encompass overgrowth, but also have a variety of other clinical manifestations (neurologic, musculoskeletal, skin, and accompanying tumors).
Journal of Clinical Medicine · 2024 · 4 citations · open access
A Patient Case of Malan Syndrome Involving 19p13.2 Deletion of NFIX with Longitudinal Follow-Up and Future Prospectives
AbstractBackground and Objectives: Malan syndrome is a rare overgrowth syndrome resulting from NFIX haploinsufficiency due to heterozygous loss-of-function mutations or microdeletions of NFIX on chromosome 19 at p13.2. Phenotypic presentation can vary but is characterized by macrocephaly, long and slender body habitus, skeletal abnormalities, and intellectual disability. Methods: Here, we report on the presentation, management, and development of a patient with Malan syndrome, highlighting the clinical and behavioral aspects of this syndrome, therapeutic interventions employed, and the course of disease over a 15-year period. We review medical records, cytogenetic analysis and neuropsychologic testing results, as well as speech pathology, optometric, and medical reports. In addition, we discuss personalized therapeutic strategies that could potentially be exploited in the future for such overgrowth syndromes. Results: To our knowledge, this is the first longitudinal follow-up report of a case of Malan syndrome to highlight the clinical course, interventions employed, and resulting improvements in neurocognitive function over time. Conclusions: This case highlights the importance of early diagnosis, intervention, and preventative care in overgrowth syndromes, as well as the potential for therapeutic intervention in the future.
American Journal of Medical Genetics Part A · 2024 · 3 citations · open access
Novel molecular mechanism in Malan syndrome uncovered through genome sequencing reanalysis, exon‐level Array, and <scp>RNA</scp> sequencing
AbstractThe NFIX gene encodes a DNA-binding protein belonging to the nuclear factor one (NFI) family of transcription factors. Pathogenic variants of NFIX are associated with two autosomal dominant Mendelian disorders, Malan syndrome (MIM 614753) and Marshall-Smith syndrome (MIM 602535), which are clinically distinct due to different disease-causing mechanisms. NFIX variants associated with Malan syndrome are missense variants mostly located in exon 2 encoding the N-terminal DNA binding and dimerization domain or are protein-truncating variants that trigger nonsense-mediated mRNA decay (NMD) resulting in NFIX haploinsufficiency. NFIX variants associated with Marshall-Smith syndrome are protein-truncating and are clustered between exons 6 and 10, including a recurrent Alu-mediated deletion of exons 6 and 7, which can escape NMD. The more severe phenotype of Marshall-Smith syndrome is likely due to a dominant-negative effect of these protein-truncating variants that escape NMD. Here, we report a child with clinical features of Malan syndrome who has a de novo NFIX intragenic duplication. Using genome sequencing, exon-level microarray analysis, and RNA sequencing, we show that this duplication encompasses exons 6 and 7 and leads to NFIX haploinsufficiency. To our knowledge, this is the first reported case of Malan Syndrome caused by an intragenic NFIX duplication.
Oxford University Press eBooks · 2019 · 0 citations
Malan Syndrome
AbstractThe chapter discusses the clinical phenotype and the molecular abnormalities in Malan syndrome, an overgrowth condition caused by mutations in the <italic>NFIX</italic> gene. Overgrowth in Malan syndrome can be present at birth, especially in terms of large head circumference, and it continues after birth, although statural growth velocity decreases with age. The syndrome is also characterized by dysmorphic facial traits, skeletal abnormalities, intellectual disability, visual problems, and advanced bone age. This condition is allelic to another overgrowth disorder, Marshall-Smith syndrome, with which it shares several clinical features and should be considered in the differential diagnosis. The causative gene for both conditions, <italic>NFIX</italic>, encodes the nuclear factor one X-type transcription factor, which regulates the growth of several types of connective tissues.
Clinical diagnosis and treatment progress of overgrowth in children and adolescents
AbstractOvergrowth in children and adolescents are not rare.The cause of overgrowth includes physiological and pathological growth accelerating.Physiological overgrowth contains familial tall stature and obesity.Pathological overgrowth includes endocrine metabolism diseases, chromosomal abnormalities, and a variety of genetic syndromes.Most patients were neglected.The standardized diagnosis and treatment for overgrowth is especially essential.In this review, the etiology and the progress of diagnosis and treatment for overgrowth were concluded in children and adolescents.
Key words:
Overgrowth; Etiology; Syndrome; Treatment
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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