DeCure for Skin creases, congenital symmetric circumferential, 2
DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for skin creases, congenital symmetric circumferential, 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 moduleSkin creases, congenital symmetric circumferential, 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 skin creases, congenital symmetric circumferential, 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
tubulin beta class I (TUBB) — TUBB 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7TTT · 2.9 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Mutations in fibrillin-1 cause stiff skin syndrome, an autosomal dominant congenital form of scleroderma. The mutations occur in the Arg-Gly-Asp sequence-encoding domain that mediates integrin binding. In stiff skin syndrome, altered cell-matrix interactions accompany excessive microfibrillar deposition, impaired elastogenesis, and increased TGFbeta concentration and signalling in the dermis. Similar findings have been observed in systemic sclerosis, a more common acquired form of scleroderma. A 3-year-old boy with circumferential skin creases, hearing impairment, undescended testes, short stature, and mental handicap was reported in 2003. Skin biopsy from his inguinal region showed degenerative collagen, which had not been found in Michelin tire baby syndrome. The authors proposed the acronym HITCH syndrome for this combination of features.
A 7-month-old girl described in 2011 had symmetrical congenital circumferential skin folds, dysmorphic features, nasal pyriform aperture stenosis, ventricular septal defect, absent spleen, camptodactyly, and severe psychomotor retardation. Skin biopsy showed subcutaneous fat extending into the superficial and deep reticular dermis. Sequencing of CDON, SHH, ZIC2, SIX3, and TGIF genes did not reveal pathogenic alterations. The authors stated that an extensive review of previously described syndromic cases did not find a similar combination of clinical and histopathological findings. No drug treatment is mentioned in any of these reports.
A 2002 surgical paper describes axillary skin crease incision for thoracotomies in 26 neonates and children, used for oesophageal atresia, patent ductus arteriosus, congenital cystic adenomatoid malformation, neuroblastoma, teratoma, and pulmonary operations including lobectomies. In a comparison of seven neonates with oesophageal atresia operated through axillary skin crease incision versus seven through postero-lateral incision, there were no significant differences in duration of procedure, duration of postoperative ventilation, or incidence of anastomosis stricture. This paper concerns surgical technique, not drug treatment for the underlying condition.
What is missing: no drug has been studied for this disease. No clinical trial, no patient stratification, no funding for a therapeutic approach. The genetic and histopathological findings point to fibrillin-1, TGFbeta signalling, and collagen abnormalities, but no compound has been tested in patients with congenital circumferential skin folds.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science Translational Medicine · 2010 · 241 citations
Mutations in Fibrillin-1 Cause Congenital Scleroderma: Stiff Skin Syndrome
AbstractThe predisposition for scleroderma, defined as fibrosis and hardening of the skin, is poorly understood. We report that stiff skin syndrome (SSS), an autosomal dominant congenital form of scleroderma, is caused by mutations in the sole Arg-Gly-Asp sequence-encoding domain of fibrillin-1 that mediates integrin binding. Ordered polymers of fibrillin-1 (termed microfibrils) initiate elastic fiber assembly and bind to and regulate the activation of the profibrotic cytokine transforming growth factor-beta (TGFbeta). Altered cell-matrix interactions in SSS accompany excessive microfibrillar deposition, impaired elastogenesis, and increased TGFbeta concentration and signaling in the dermis. The observation of similar findings in systemic sclerosis, a more common acquired form of scleroderma, suggests broad pathogenic relevance.
European Journal of Pediatric Surgery · 2002 · 22 citations
The Use of Axillary Skin Crease Incision for Thoracotomies of Neonates and Children
AbstractUNLABELLED: Because of the complications due to "standard" postero-lateral thoracotomy, i.e. winged scapula, scoliosis etc., different muscle-sparing approaches have been published. In 1998 Bianchi et al published their work on axillary skin crease incision for neonates, primarily for the treatment of oesophageal atresia. AIM OF THE STUDY: To assess the usefulness of axillary skin crease incision in paediatric surgery. METHODS: Data of 26 cases with axillary skin crease incision were reviewed and the results compared to those of postero-lateral incisions. RESULTS: Axillary skin crease incision in both neonates and children (up to the age of 15 years) was used to treat both pulmonary and mediastinal lesions and both benign and malignant diseases. The authors performed 17 operations in neonates (8 oesophageal atresia with tracheo-oesophageal fistula, 8 patent ductus arteriosus, 1 congenital cystic adenomatoid malformation) and 9 operations in children (3 neuroblastoma, 1 teratoma, 5 pulmonary operations including lobectomies). The authors were able to perform all operations with unrestricted access through the axillary skin crease incision when the 3rd or 4th intercostal space was necessary for the thoracotomy. The authors compared patients operated with oesophageal atresia through an axillary skin crease incision with patients operated through a postero-lateral incision - seven neonates each. There were no significant differences in the results regarding duration of procedure, duration of postoperative ventilation or the incidence of anastomosis stricture. CONCLUSIONS: Although further long-term studies are necessary to evaluate the axillary skin crease incision, the authors believe that axillary skin crease incision should become the standard method for 3rd and 4th intercostal space thoracotomies in neonates and children.
American Journal of Medical Genetics Part A · 2003 · 14 citations
Hearing impairment, undescended testis, circumferential skin creases, and mental handicap (HITCH) syndrome: A case report
AbstractWe report on a 3-year-old boy with circumferential skin creases as seen in Michelin tire baby syndrome (MTBS), hearing impairment, undescended testes, short stature, and mental handicap. Skin biopsy from the inguinal region showed degenerative collagen, which has never been found in MTBS. Similar clinical manifestations shared by our patient and a boy reported previously suggest a new clinical entity, in which degenerative collagen is etiologically involved. We propose an acronym to designate it: hearing impairment, undescended testis, circumferential skin creases, and mental handicap (HITCH) syndrome.
New Syndrome of Congenital Circumferential Skin Folds Associated with Multiple Congenital Anomalies
AbstractCongenital circumferential skin folds can be found in individuals with no additional defects, as well as in patients with multiple congenital anomalies and developmental abnormalities. Current data point to etiological heterogeneity of syndromic cases. We describe a 7-month-old girl with a novel combination of symmetrical congenital circumferential skin folds, dysmorphic features, and multiple congenital abnormalities. Examination of the patient revealed symmetrical congenital circumferential skin folds and dysmorphic features, as well as multiple congenital anomalies including nasal pyriform aperture stenosis, ventricular septal defect, absent spleen, camptodactyly, and severe psychomotor retardation. Skin biopsy demonstrated subcutaneous fat extending into the superficial and deep reticular dermis. Sequencing of the CDON, SHH, ZIC2, SIX3, and TGIF genes (associated with holoprosencephaly) did not disclose pathogenic alterations. Extensive review of previously described cases of syndromic congenital circumferential skin folds did not reveal a similar combination of clinical and histopathological findings.
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.
