DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for van Maldergem syndrome 2 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleVan Maldergem syndrome 2 maps to a 2-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 van maldergem syndrome 2 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
FAT atypical cadherin 4 (FAT4) — FAT4 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 cacdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8EGW · 2.3 Å · ligand CACODYLATE ION (CAC). Experimental structure, not a prediction.
What the evidence adds up to
Van Maldergem syndrome is an autosomal disorder reported in only 13 patients as of 2017, characterised by intellectual disability, typical craniofacial features, auditory malformations, hearing loss, skeletal and limb malformations, and brain abnormalities including periventricular neuronal heterotopia. The first description in 1992 involved a girl with facial abnormalities (telecanthus, epicanthus, broad flattened nose, large inverted W-shaped mouth, malformed ears), hand malformations (camptodactyly, clinodactyly, interdigital webbing), joint hyperlaxity, and mental retardation. A 1997 report of a male patient with consanguineous parents added genital malformations (micropenis, bifid scrotum, cryptorchidism), inguinal hernia, pharyngeal instability requiring tracheostomy, hip subluxation, small kidneys, severe feeding difficulties requiring permanent tube feeding, and talipes equinovarus. Metabolic tests and chromosomal analysis (450-500 bands; 46,XY) were normal; molecular karyotyping found two parental CNVs (paternal 9q33.1 deletion, maternal 11p15.1 duplication) considered unlikely to contribute to the phenotype.
A 2017 case report described a female patient with compound heterozygous variants in DCHS1 (rs145099391:G>A, p.P197L and rs753548138:G>A, p.T2334M), diagnostic of van Maldergem syndrome type 1. At age 4 she had intellectual disability, craniofacial features, and auditory malformations. At age 15 she had no breast development and findings consistent with hypogonadotropic hypogonadism. At age 37 whole exome sequencing identified the DCHS1 variants. The authors noted that two previously published patients with van Maldergem syndrome may also have had hypogonadotropic hypogonadism, but endocrine abnormalities were not evaluated or mentioned in those earlier reports. The molecular genetic basis for the endocrine anomalies observed in some patients remains unexplained.
No drug treatments are mentioned in any of these abstracts. The syndrome is defined entirely by its clinical features and, in one case, by DCHS1 mutations. What is missing is any systematic investigation of endocrine function across patients, any molecular explanation for the endocrine findings, any animal model work, and any therapeutic trials. The total number of reported patients is too small for natural history studies, and no patient stratification by genotype or endocrine status has been attempted. Funding for such rare-disease work is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Texas Journal of Science · 1997 · 41 citations
Trinacromerum bonneri, new species, last and fastest pliosaur of the western interior seaway
AbstractWe report on a male patient with the proposed diagnosis of the rare but very distinct entity of van Maldergem syndrome. His parents are first cousins. At the age of 4 years the boy presented with severe developmental delay, talipes equinovarus, finger camptodactyly with interphalangeal pterygium, joint laxity, bilateral microtia, and a dysmorphic facies. He showed bilateral epicanthus, telecanthus, short palpebral fissures, broad flat nasal bridge, and dental malocclusion. The combination of the specific facial features with camptodactyly, interphalangeal pterygium, joint laxity and developmental delay led to the diagnosis of van Maldergem syndrome. The medical history was further on significant for pharyngeal instability requiring the placement of a tracheostomy tube, an inguinal hernia, hip subluxation, small kidneys and genital abnormalities (micropenis, bifid scrotum, cryptorchidism). Due to severe feeding difficulties permanent tube feeding was required. Metabolic tests (newborn metabolic screening, 7-dehydrocholesterol, amino acids, organic acids in urine) and chromosomal analysis (450-500 bands; 46,XY) were normal. Molecular karyotyping revealed two parental CNVs (paternal deletion of 9q33.1; maternal duplication of 11p15.1), which are unlikely to contribute to the patient's phenotype. Taken together, the report on a further patient with van Maldergem syndrome expands the clinical spectrum of the condition by adding genital malformations, hernia, pharyngeal instability, and subluxation of the hip.
Mental retardation with blepharo‐naso‐facial abnormalities and hand malformations: a new syndrome?
AbstractVan Maldergem L, Wetzburger C, Verloes A, Fourneau C, Gillerot Y. Mental retardation with blepharo‐naso‐facial abnormalities and hand malformations: a new syndrome. Clin Genet 1992:41: 22–24. A syndrome involving facial abnormalities (telecanthus, epicanthus, broad flattened nose, large inverted W‐shaped mouth and malformed ears), malformed extremities (camptodactyly, clinodactyly, interdigital webbing and joint hyperlaxity) and mental retardation is described in a girl at birth and at 11 years old. A comparison with Pashayan‐Pruzansky syndrome, fetal alcohol syndrome, VATER association, Marden‐Walker syndrome and Tel‐Hashomer syndrome is discussed. We suggest this patient represents a new malformation syndrome or an extreme pheno‐typic variant of one of the above‐mentioned syndromes.
A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia
AbstractAbstract Background We report a female patient with endocrine abnormalities, hypogonadotropic hypogonadism and amazia (breasts aplasia/hypoplasia but normal nipples and areolas) in a rare syndrome: Van Maldergem syndrome (VMS). Case presentation Our patient was first evaluated at age 4 for intellectual disability, craniofacial features, and auditory malformations. At age 15, she presented with no breast development and other findings consistent with hypogonadotropic hypogonadism. At age 37, she underwent whole exome sequencing (WES) to identify pathogenic variants. WES revealed compound heterozygous variants in DCHS1 (rs145099391:G > A, p.P197L & rs753548138:G > A, p.T2334 M) [RefSeq NM_003737.3], diagnostic of Van Maldergem syndrome (VMS-1). VMS is a rare autosomal disorder reported in only 13 patients, characterized by intellectual disability, typical craniofacial features, auditory malformations, hearing loss, skeletal and limb malformations, brain abnormalities with periventricular neuronal heterotopia and other variable anomalies. Our patient had similar phenotypic abnormalities. She also had hypogonadotropic hypogonadism and amazia. Based on the clinical findings reported, two previously published patients with VMS may also have been affected by hypogonadotropic hypogonadism, but endocrine abnormalities were not evaluated or mentioned. Conclusion This case highlights an individual with VMS, characterized by compound heterozygous variants in DCHS1. Our observations may provide additional information on the phenotypic spectrum of VMS, including hypogonadotropic hypogonadism and amazia. However, the molecular genetic basis for endocrine anomalies observed in some VMS patients, including ours, remains unexplained.
A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia
AbstractAbstract Background We report a female patient with endocrine abnormalities, hypogonadotropic hypogonadism and amazia (breasts aplasia/hypoplasia but normal nipples and areolas) in a rare syndrome: Van Maldergem syndrome (VMS). Case presentation Our patient was first evaluated at age 4 for intellectual disability, craniofacial features, and auditory malformations. At age 15, she presented with no breast development and other findings consistent with hypogonadotropic hypogonadism. At age 37, she underwent whole exome sequencing (WES) to identify pathogenic variants. WES revealed compound heterozygous variants in DCHS1 (rs145099391:G > A, p.P197L & rs753548138:G > A, p.T2334 M) [RefSeq NM_003737.3], diagnostic of Van Maldergem syndrome (VMS-1). VMS is a rare autosomal disorder reported in only 13 patients, characterized by intellectual disability, typical craniofacial features, auditory malformations, hearing loss, skeletal and limb malformations, brain abnormalities with periventricular neuronal heterotopia and other variable anomalies. Our patient had similar phenotypic abnormalities. She also had hypogonadotropic hypogonadism and amazia. Based on the clinical findings reported, two previously published patients with VMS may also have been affected by hypogonadotropic hypogonadism, but endocrine abnormalities were not evaluated or mentioned. Conclusion This case highlights an individual with VMS, characterized by compound heterozygous variants in DCHS1. Our observations may provide additional information on the phenotypic spectrum of VMS, including hypogonadotropic hypogonadism and amazia. However, the molecular genetic basis for endocrine anomalies observed in some VMS patients, including ours, remains unexplained.
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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