DeCure for Terminal osseous dysplasia-pigmentary defects syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for terminal osseous dysplasia-pigmentary defects 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 moduleTerminal osseous dysplasia-pigmentary defects 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 terminal osseous dysplasia-pigmentary defects 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
filamin A (FLNA) — FLNA 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 diodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2J3S · 2.5 Å · ligand 1,4-DIETHYLENE DIOXIDE (DIO). Experimental structure, not a prediction.
What the evidence adds up to
Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome. A 2010 study of a four-generation pedigree reported that the phenotype is highly variable, suggesting X-inactivation plays an important role. The same study refined the linkage region to Xq28 and excluded two candidate genes, FLNA and FAM58A. A 2014 study then identified a recurrent mutation, c.5217G>A, in the FLNA gene in three families with TODPD, and found possible germline and somatic mosaicism in two of those three families. A 2013 case report states that FLNA gene mutation, with X-linked dominant transmission, is the aetiology of this pathology, and that the gene codes for filamin A, a protein essential in cytoskeleton formation.
The 2010 follow-up of the first reported family noted that although the most striking features involve the hands and feet, the skeletal involvement is more generalised and affects many other areas. The 2013 case report describes published cases as rare, with only 19 patients from nine different families at that time, plus exceptional isolated cases. Clinical findings defining the condition include multiple digital fibromas, dental anomalies, osseous alterations, and dysmorphic changes. The 2014 study states that the occurrence of somatic and germline mosaicism indicates caution should be taken in counselling recurrence risks upon presentation of an isolated case.
Regarding treatment, the 2013 case report notes that fibromas associated with infantile digital fibromatosis have a high risk of recurrence when removed and tend to autoresolve with time. For fibromas associated with digitocutaneous dysplasia, the response to excision or other treatments is still not well defined. A 2021 paper on surgical management of craniomaxillofacial features in the broader otopalatodigital spectrum disorders describes a four-step treatment of malformations with good outcomes both aesthetically and functionally, without complication, in two patients with FLNA mutations, but this is not specific to TODPD.
What is still missing is a specific treatment for TODPD itself. No drug therapy is mentioned in any of these abstracts. The natural history of the digital fibromas—whether they autoresolve in TODPD as they do in isolated infantile digital fibromatosis—remains unclear. The small number of reported patients limits any systematic trial. Patient stratification by specific FLNA mutation and by the degree of somatic mosaicism would be needed before any intervention could be tested.
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 · 2010 · 10 citations · open access
Terminal osseous dysplasia with pigmentary defects (TODPD): Follow‐up of the first reported family, characterization of the radiological phenotype, and refinement of the linkage region
AbstractTerminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies and pigmentary skin defects. We have previously described this syndrome in several females from a large, four-generation pedigree. The presentation in the affected patients included multiple anomalies, hypertelorism, iris colobomas, punched-out pigmentary abnormalities over the face and scalp, brachydactyly, and digital fibromatosis. The phenotype was highly variable thus suggesting that X-inactivation plays an important role in the expression of the disease. Following our initial description of this condition there have been reports of more cases supporting the initial phenotypic description of this disease. We report on the follow-up of this family at about 10 years from the first evaluation. A detailed clinical follow-up and a review of the skeletal surveys suggests that although the most striking features involves the hands and feet, the skeletal involvement is more generalized and affects many other areas. Our previous linkage analysis has demonstrated mapping to Xq27.3-Xq28. Using a 6,056 SNP array, we have further refined the critical region within the Xq28 region. We have also excluded two candidate genes (FLNA and FAM58A) mapping in the critical region. The identification of the gene responsible for this rare condition will shed light on the molecular pathways leading to the various congenital anomalies of TODPD and will allow a more accurate genetic counseling to the affected individuals.
Diagnosis and Treatment of Digitocutaneous Dysplasia, a Rare Infantile Digital Fibromatosis: A Case Report
AbstractDigitocutaneous dysplasia, also termed osseous terminal dysplasia with pigmentary defects, is a recently described pathology. In 1974, Bloem et al. [5] discussed the association between digital fibromas and pigmentary lesions. In 1998, Horii et al. [13] published a case report with similar characteristics associated with facial dysmorphia and metacarpal involvement. These authors were the first to describe a syndrome that embraced all these features. Recently, in 2010, Sun et al. [28] published the etiology of this pathology, FLNA gene mutation, with X-linked dominant transmission. This gene codifies filamin A, a protein essential in cytoskeleton formation.
Published cases with digitocutaneous dysplasia are rare, with only 19 patients from nine different families [2, 3, 6, 7, 19, 21, 30], with exceptional isolated cases [15, 20]. In all of these cases, there were similar clinical findings that defined digitocutaneous dysplasia, such as multiple digital fibromas, dental anomalies, osseous alterations, and dysmorphic changes [13].
Fibromas associated with infantile digital fibromatosis have a high risk of recurrence when they are removed and they tend to autoresolve with time [20]. For fibromas associated with dysplasia digitocutaneous, the response to excision or other treatments is still not well defined. Consultation of a newborn female in our center, who presented with severe digital fibromas, encouraged us to carefully review the literature and examine the therapeutic possibilities.
Molecular Genetics & Genomic Medicine · 2014 · 4 citations · open access
Terminal osseous dysplasia with pigmentary defects (<scp>TODPD</scp>) due to a recurrent filamin A (<scp>FLNA</scp>) mutation
AbstractTerminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies, pigmentary skin defects, digital fibromas, and generalized bone involvement due to a recurrent mutation in the filamin A (FLNA) gene. We here report the mutation c.5217G>A in FLNA in three families with TODPD and we found possible germline and somatic mosaicism in two out of the three families. The occurrence of somatic and germline mosaicism for TODPD indicates that caution should be taken in counseling recurrence risks for these conditions upon presentation of an isolated case.
Journal of Craniofacial Surgery · 2021 · 0 citations
Surgical Management of Craniomaxillofacial Features in the Otopalatodigital Spectrum Disorders
AbstractABSTRACT: Otopalatodigital syndrome spectrum disorders are caused by Filamin A (FLNA) gene mutations. Otopalatodigital syndrome spectrum disorders are a group of rare congenital skeletal dysplasia, with specific craniomaxillofacial features including otopalatodigital syndrome type 1 and type 2, Melnick-Needles syndrome, frontometaphyseal dysplasia, terminal osseous dysplasia with pigmentary defects. The authors describe cases of a young girl with Melnick-Needles syndrome and a young boy with frontometaphyseal dysplasia treated in the Oral and Maxillofacial Surgery Department. Both patients had FLNA gene mutation confirmed with molecular genetic analysis. The authors proposed a 4 step treatment of the malformations with good outcomes both aesthetically and functionally, without complication.
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.
