DeCure for Contractures, pterygia, and variable skeletal fusions syndrome 1B
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for contractures, pterygia, and variable skeletal fusions syndrome 1B — 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 moduleContractures, pterygia, and variable skeletal fusions syndrome 1B 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 contractures, pterygia, and variable skeletal fusions syndrome 1b 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.
What the evidence adds up to
Contractures, pterygia, and variable skeletal fusions syndrome 1B is a condition that overlaps with the multiple pterygium syndromes described in a 1982 review of over 350 infants with arthrogryposis. Among those infants, seven had the autosomal recessively inherited multiple pterygium syndrome, including three sibs, one child of consanguineous parents, and three isolated cases. These seven patients had multiple joint webs, unusual finger contractures, syndactyly, rocker bottom feet, ptosis, antimongoloid slant of palpebral fissures, epicanthal folds, highly arched palate, scoliosis, and short stature, with intrafamilial variability noted. Three patients from one family had a lethal multiple pterygium syndrome, including monozygotic twins with webbing and contractures of elbows, knees, neck, and fingers, calcaneovalgus foot deformity, hypertelorism, flat nose, antimongoloid slant, low-set ears, and internal malformations such as bilateral pulmonary hypoplasia, small heart, absence of the appendix, and attenuation of the ascending and transverse colon. One sporadic case of lethal popliteal pterygium with facial clefts was also reported, with ankyloblepharon filiforme adnatum, hypoplasia of nasal cartilages, frenula, clefts into the oropharynx, large popliteal pterygia, syndactyly with fusion of all digits, and hypoplastic labia.
A 2024 report identified biallelic variants in MYH3 as a cause of recessively inherited arthrogryposis in two affected sibs born to unaffected, distantly related parents. Both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro), and sequencing of 169 other arthrogryposis genes yielded no other compelling candidate variants. This was the first report of biallelic MYH3 variants causing a distal arthrogryposis phenotype without the additional features of contractures, pterygia, and spondylocarpotarsal fusion syndromes (CPSFS), which are also caused by MYH3 variants in both dominant and recessive forms. Heterozygous MYH3 variants had previously been linked to dominantly inherited distal arthrogryposis conditions including Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome.
A 2014 prenatal sonography case study described multiple pterygia, flexion contractures, and skeletal abnormalities consistent with multiple pterygium syndrome or Escobar syndrome, noting that differentiating lethal from nonlethal skeletal dysplasias prenatally can improve patient care. No treatment or intervention is reported in any of these abstracts. What remains missing are prospective natural history studies with standardised phenotyping, functional validation of the specific MYH3 variants, and any clinical trial infrastructure for this ultra-rare recessive condition.
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 · 1982 · 173 citations
Limb pterygium syndromes: A review and report of eleven patients
AbstractConditions with limb pterygia and congenital contractures were reviewed as part of a study of over 350 infants with arthrogryposis. Emphasis was placed on inheritance and variability of distinct pterygium conditions. Eleven patients with limb pterygia were recognized in our study and are described here. Seven of the 350 patients with congenital contractures had the autosomal recessively inherited multiple pterygium syndrome (Patients 1-7). Three of the seven are sibs, a fourth was born to consanguineous parents, and three were chance isolated cases. These seven had multiple joint webs, unusual finger contractures, syndactyly, rocker bottom feet, ptosis, antimongoloid slant of palpebral fissures, epicanthal folds, highly arched palate, scoliosis, and short stature. There is intrafamilial variability. Three patients from one family had a lethal multiple pterygium syndrome. Two were monozygotic twins. They had webbing and contractures of the elbows, knees, neck, and fingers, calcaneovalgus deformity of the feet, and an unusual facial appearance: hypertelorism, flat nose, antimongoloid slant of palpebral fissures, apparently low-set ears. One had a cleft palate. Internal malformations included: bilateral pulmonary hypoplasia, small heart, absence of the appendix, and attenuation of the ascending and transverse colon. One sporadic case of lethal popliteal pterygium with facial clefts was studied. Multiple anomalies included: ankyloblepharon filiforme adnatum, upslanting palpebral fissures, hypoplasia of nasal cartilages, frenula, clefts into the oropharynx lateral to the mouth, apparently low-set ears with slit-like canals, large popliteal pterygia, syndactyly with fusion of all digits in hands and feet, and hypoplastic labia.
Clinical Genetics · 2024 · 3 citations · open access
Bi‐allelic variants in <scp>MYH3</scp> cause recessively‐inherited arthrogryposis
AbstractArthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.
Journal of diagnostic medical sonography · 2014 · 2 citations · open access
Prenatal Sonographic Detection of Skeletal Dysplasias
AbstractSkeletal dysplasias are a genetically heterogeneous group of disorders that can be diagnosed prenatally by sonography. Differentiating these disorders in the prenatal period can be difficult. However, differentiating known lethal disorders from nonlethal disorders can improve patient care and plan of action. This case study presents multiple pterygia, flexion contractures, and skeletal abnormalities, which are consistent with multiple pterygium syndrome, or Escobar syndrome.
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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