DeCure for Split hand-foot malformation 1 with sensorineural hearing loss
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for split hand-foot malformation 1 with sensorineural hearing loss — 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 moduleSplit hand-foot malformation 1 with sensorineural hearing loss 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 split hand-foot malformation 1 with sensorineural hearing loss 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
distal-less homeobox 5 (DLX5) — DLX5 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 4RDU · 1.85 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Split hand-foot malformation 1 with sensorineural hearing loss is a rare autosomal dominant condition linked to the SHFM1 locus on chromosome 7q21. In two unrelated families reported in 2001, split foot malformations were found in 6 of 11 gene carriers in the larger family, with mild-to-moderate sensorineural hearing loss in 4; one individual also had split hand and cleft lip/palate, and another had tibial deficiency. In the second family, variable split foot was seen in 3 of 4 gene carriers, sensorineural deafness in 3, and one gene carrier had only deafness. The combined maximum LOD score was 4.37 at theta = 0.0 for marker D7S527 at 80% penetrance. A 2000 report described a father and daughter with bilateral foot ectrodactyly, minor fifth finger abnormalities, and severe sensorineural hearing loss, with no cytogenetic structural aberrations.
A 2023 study identified a 7q21.13-q21.3 deletion in a patient with SHFM1 and deafness that did not include the DLX5/6 genes but removed exons 15 and 17 of DYNC1I1, which act as exonic enhancers for DLX5/6. Reduced DLX5/6 expression was confirmed by RT-PCR in a patient-derived lymphoblastoid cell line. The authors found no evidence that DLX5/6 are imprinted in humans. This suggests that disruption of regulatory elements, not just the genes themselves, can cause the phenotype.
Two 2024 papers address hearing loss treatment but not the genetic syndrome directly. One describes a single infant with sensorineural hearing loss treated with foot reflexology, with brain activity changes seen on fMRI; the other reports on surgical ossicular chain reconstruction in eight children (10 ears) with congenital malformations. Average hearing threshold improved from 51.25 dB preoperatively to 31.94 dB postoperatively. Better outcomes were seen with mobile stapes footplates and without external ear malformations. No drug treatment is described in any of these abstracts.
What remains missing is a specific molecular therapy for SHFM1 with hearing loss. The causal gene or regulatory mechanism is still being defined, and no targeted treatment exists. Patient stratification by deletion type or DLX5/6 expression level has not been attempted in a clinical trial. Funding for functional studies of the 7q21 regulatory landscape and for any preclinical work on gene or enhancer therapy 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.
Clinical Genetics · 2001 · 52 citations · open access
Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21
AbstractDevelopmental anomalies of the appendicular skeleton are among the most common and easily ascertained birth defects. Split hand/split foot malformations, distinctive in having deficiency of the central rays, occur as isolated anomalies and as one component of multisystem syndromes. The clinical and molecular characterization of a new syndrome, found in two unrelated families, consisting of split foot with hearing loss, is presented here. As in other split hand/split foot conditions, variable expression and reduced penetrance is notable. In the larger family, variably expressed split foot malformations were found in 6 of 11 gene carriers. and mild-to-moderate sensorineural hearing loss in 4. Split hand and cleft lip/palate in one individual and tibial deficiency in another suggest that these malformations are uncommon components of the syndrome. Ectodermal abnormalities did not occur. In the second family, variable split foot was observed in 3 of 4 gene carriers, and sensorineural deafness was present in 3. Split hand was only seen in a gene carrier who also had split foot and deafness. One gene carrier only had deafness. The gene for split hand split foot with sensorineural hearing loss was linked to markers in 7q21 in both families, with a combined (maximum LOD score of 4.37 at theta = 0.0 for locus D7S527) at 80% penetrance. Efforts to identify the responsible gene have not yet been successful.
Split Hand-Foot and Deafness in a Patient with 7q21.13-q21.3 Deletion Not Including the DLX5/6 Genes
AbstractSplit Hand-Foot Malformation (SHFM) is a congenital limb defect characterized by a median cleft of the hands and/or feet due to the absence/hypoplasia of the central rays. It may occur as part of a syndromic condition or as an isolated malformation. The most common of the six genetic loci identified for this condition is correlated to SHFM1 and maps in the 7q21q22 region. SHFM1 is characterized by autosomal dominant transmission, incomplete penetrance and variable expressivity. Associated features often include hearing loss, intellectual disability/developmental delay and craniofacial abnormalities. Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype. Through SNP array, we analyzed a patient affected by SHFM1 associated with deafness and an abnormality of the inner ear (incomplete partition type I); we identified a deletion in 7q21, not involving the DLX5/6 genes, but including exons 15 and 17 of DYNC1I1, known to act as exonic enhancers (eExons) of the DLX5/6 genes. We further demonstrated the role of DYNC1I1 eExons in regulating DLX5/6 expression by means of showing a reduced expression of the DLX5/6 genes through RT-PCR in a patient-derived lymphoblastoid cell line. Furthermore, our data and a review of published cases do not support the hypothesis that DLX5/6 are imprinted in humans. This work is an example of how the disruption of regulatory elements can be responsible for congenital malformations.
Autosomal dominant ectrodactyly with sensorineural deafness
AbstractEctrodactyly or split hand/split foot malformation as it is now known, is a rare developmental disorder sometimes associated with other systemic malformations. Very few cases of congenital hearing loss coexisting with ectrodactyly have been reported world-wide. We profile one such family with the father and daughter being affected with bilateral foot ectrodactyly minor abnormalities of the 5th fingers and severe sensorineural hearing loss (SNHL). The inheritance in this family was likely to be autosomal dominant. There were no cytogenetically demonstrable structural aberrations in either case.
World Journal of Clinical Cases · 2024 · 0 citations · open access
Additional comments on foot reflexology treatment for sensorineural hearing loss in infant
AbstractCurrently, treatment options for infant sensorineural hearing loss (SNHL) are limited. This article describes a novel case of SNHL in an infant successfully treated with foot reflexology, along with observed brain activity changes before and after treatment, as indicated by functional magnetic resonance imaging. Hence, this commentary discusses the case and our viewpoints regarding foot reflexology for treating SNHL.
Ear Nose & Throat Journal · 2024 · 0 citations · open access
Evaluation of the Curative Effects of Surgical Intervention in Cases of Congenital Malformation of the Ossicular Chain in Children
AbstractPurpose: Congenital malformation of the ossicular chain results in challenges with hearing and language development in children. We aimed to analyze the clinical characteristics, prognosis, and surgical treatments of different types of congenital ossicular chain malformations in children. Methods: Eight cases (10 ears) treated between October 2019 and February 2022 were analyzed retrospectively. Patients were divided according to the location of the ossicular chain malformation and whether it was complicated by external ear malformation. Imaging, audiological examination, intraoperative exploration of the middle ear, and postoperative outcomes were recorded. Results: Group 1 incudostapedial joint deformity): 6 ears/60%; Group 2 (simple incus deformity): 2 ears/20%; Group 3 (simple malleus deformity): 2 ears/20%; Group A (with external ear malformations): 4 ears/40%; Group B (without external ear malformations): 6 ears/60%. The average hearing threshold before and after the operation was 51.25 ± 12.88 and 31.94 ± 12.96 dB, respectively. There were differences in the intervention effects of different malformed sites (Group 1: t = 5.139, P = .004; Group 2: t = 13.500, P = .047; Group 3: t = 15.000, P = .042). The effect of the intervention in cases of malformation with mobile stapes footplates was better than that with immobile stapes footplates ( t = 4.082, P = .027). The effect of the intervention without external ear malformations was better than that with external ear malformations ( t = 7.706, P = .001). Conclusions: The intervention yielded superior results in cases of malformation with mobile stapes footplates compared to those with immobile stapes footplates. Different intervention strategies should be determined through precise deformity assessments, with the degree of stapes mobility serving as a crucial factor in improving the prognosis.
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.
