DeCure for Craniometaphyseal dysplasia, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for craniometaphyseal dysplasia, autosomal recessive — 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 moduleCraniometaphyseal dysplasia, autosomal recessive 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 craniometaphyseal dysplasia, autosomal recessive 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
gap junction protein alpha 1 (GJA1) — GJA1 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 7Z1T · 2.26 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1983 report describes a Mexican family with autosomal dominant craniometaphyseal dysplasia, noting wide clinical variability: the proband had striking cranial changes but only moderate long bone abnormalities, while his father and sister had mild cranial changes and characteristic metaphyseal widening. A 1977 review classifies craniometaphyseal dysplasia as one of the craniotubular bony dysplasias, stating that the recessive form is more severe, with nasal obstruction, cranial nerve palsies including optic atrophy and hearing loss, mandibular enlargement, and metaphyseal flaring on X-ray. The same review notes a patient who underwent mastoid surgery and later developed contralateral temporary facial paresis, with no further deterioration at last follow-up.
A 2000 study reports a four-generation inbred family with ten individuals affected by an autosomal recessive craniotubular dysplasia, most likely recessive craniometaphyseal dysplasia. All affected patients were born to consanguineous healthy parents, and the equal sex ratio and absence of affected offspring from affected individuals support recessive inheritance. Through genome-wide scanning, the authors mapped the recessive craniometaphyseal dysplasia locus to a 7 cM interval between D6S302 and D6S1639 at chromosome region 6q21-22, and excluded the COL10A1 gene as the cause. They also observed that a form of recessive spondylocostal dysplasia segregated separately in the same family, with one individual having both conditions, and found no linkage to the DLL3 gene on 19q13, implying genetic heterogeneity for recessive spondylocostal dysplasia.
A 2011 report describes a female patient with craniometaphyseal dysplasia phenotype, born to healthy first-degree cousins, who showed homozygosity for polymorphic markers at the 6q21-22 locus, further supporting the existence of an autosomal recessive form and expanding its clinical spectrum to a more severe phenotype. The authors note that the dominant form is associated with mutations in the ANKH gene, but the gene for the recessive form remains unknown. A 1983 paper on osteoglophonic dwarfism describes a father and son with severe craniofacial deformities, craniosynostosis, multiple lucent metaphyseal defects, vertebral flattening and anterior beaking, and abnormal dentition, suggesting autosomal dominant inheritance; this is a separate condition from craniometaphyseal dysplasia.
What is still missing is identification of the specific gene responsible for autosomal recessive craniometaphyseal dysplasia, which would require further sequencing and functional studies within the mapped 6q21-22 region. No clinical trials or treatment data exist for this condition; the literature consists entirely of case reports and linkage mapping. Patient stratification by genotype is impossible until the gene is found, and funding for such rare disease genetics work remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractThe autosomal dominant form of craniometaphyseal dysplasia was ascertained in three members of a Mexican family. The clinical and radiological features of the affected members are described and the variability of the condition is emphasized. The proband has striking cranial changes, but moderate long bone abnormalities; the father and the sister, who had mild cranial changes, showed the characteristic metaphyseal widening.
American Journal of Medical Genetics · 1998 · 18 citations
Craniometaphyseal dysplasia in six generations of a German kindred
AbstractCraniometaphyseal dysplasia (CMD) was found in 6 generations of a large German kindred; 24 affected individuals were identified. The clinical diagnosis was confirmed by further examinations in 15 individuals, including 2 exhumed skeletons. Five deceased individuals were considered to be undoubtedly affected by reviewing photographs, and 4 must have had CMD from genealogical considerations. Pedigree analysis was performed over 8 generations back to persons born at the beginning of the 18th century in a central area of Germany. The trait could be traced back to a common male ancestor, born in 1790. Molecular genetic investigations on 3 generations of this kindred are in progress. In the present study we describe the clinical characteristics of the family.
Journal of Medical Genetics · 1983 · 15 citations · open access
Osteoglophonic dwarfism in two generations.
AbstractA father and son, both affected by a skeletal dysplasia with severe craniofacial deformities, are reported and compared to three previously described isolated cases of the same dwarfism. The principal features are craniosynostosis, multiple lucent metaphyseal defects, flattening and anterior beaking of the vertebral bodies, and abnormal dentition. Autosomal dominant inheritance is suggested.
American Journal of Medical Genetics Part A · 2011 · 11 citations · open access
Craniometaphyseal dysplasia with severe craniofacial involvement shows homozygosity at 6q21‐22.1 locus
AbstractCraniotubular dysplasias (CTD) are a heterogeneous group of genetic disorders of skeletal development, whose clinical and etiological classification is still much debated. One of the most common form is the autosomal dominant craniometaphyseal dysplasia (CMD) which is associated with mutation in the ANKH gene. In the literature a few families are reported with CMD phenotype that suggest an autosomal recessive (AR) pattern of inheritance. A candidate locus at 6q21-22 has been mapped in a large inbred Brazilian family, but the gene of the recessive form is still unknown. Our data on a female patient with CMD phenotype, born from healthy first degree cousins and displaying homozygosity for polymorphic markers at the 6q21-22 locus, further support the existence of an AR CMD, expanding its clinical spectrum to a more severe phenotype.
The Journal of Laryngology & Otology · 1977 · 8 citations
Craniometaphyseal dysplasia
AbstractAbstract A case report of craniometaphyseal dysplasia is presented with a classification of this disease, supported by a review of the literature. Certain unusual features are observed—mastoid surgery and later contralateral temporary facial paresis. The patient showed no further deterioration of symptoms when last reviewed. Craniometaphyseal dysplasia is one of a number of craniotubular bony dysplasias. These dysplasias are characterized by (a) genetic transmission and (b) dysplastic or hyperostotic involvement of the cranial and tubular bones (Gorlin, et al. , 1969). Craniometaphyseal dysplasia may be dominant or recessive in form, the latter being more severe in its clinical manifestations, viz. nasal obstruction and deformity and cranial nerve palsies, such as optic atrophy and loss of hearing. There may also be enlargement of the mandible and flaring of the metaphyses of long bones on X-ray examination.
UNIFESP Institutional Repository (Universidade Federal de São Paulo) · 2000 · 0 citations
Mapping of the autosomal recessive (AR) craniometaphyseal dysplasia locus to chromosome region 6q21-22 and confirmation of genetic heterogeneity for mild AR spondylocostal dysplasia
AbstractWe report on a four-generation inbred family including 10 individuals affected with a form of craniotubular dysplasia (CTD), All affected patients were born to consanguineous healthy parents; this finding, together with the equal sex ratio among affected individuals and the occurrence of only normal individuals among their offspring, indicates that the disease in this family is an autosomal recessive (AR) trait, Taking into account the segregation pattern of the disease in the family and the radiological characteristics of two young CTD patients, the most likely diagnosis for the defect is AR cranio-metaphyseal dysplasia (CMD), CMD is a CTD, with both autosomal dominant (AD) and recessive forms, the description of the present genealogy confirms the AR pattern of inheritance of some cases of CMD and contributes to a better delineation of the clinical spectrum of AR CMD, suggesting a more pronounced diaphyseal involvement in the AR compared with the AD CMD, Through genomewide scanning, we mapped the AR CMD to a 7 cM interval, between D6S302 and D6S1639, at 6q21-22 region, We have also excluded the positional candidate COL10A1 gene as being the responsible for this disorder. Curiously, a form of AR spondylocostal dysplasia (SD) also segregates in the family, including one affected individual with both conditions. the gene DLL3, mapped to 19q13 region, was recently found to be responsible for one form of AR SD; however, we did not find evidence of linkage between this 19q region and the SD segregating in our family, thus implying in genetic heterogeneity for AR SD. (C) 2000 Wiley-Liss, Inc.
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.
