DeCure for Autosomal recessive Kenny-Caffey syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive Kenny-Caffey 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 moduleAutosomal recessive Kenny-Caffey 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 autosomal recessive kenny-caffey 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
tubulin folding cofactor E (TBCE) — TBCE 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9M1M · 2.21 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Kenny-Caffey syndrome is a rare hereditary disorder characterised by short stature, hypoparathyroidism, and electrolyte disturbances. Two genetic forms exist: KCS1 caused by pathogenic variants in TBCE, and KCS2 caused by variants in FAM111A. A 1992 report described two sibs born to consanguineous parents with manifestations including dwarfism, internal cortical thickening and medullary stenosis of tubular bones, poorly ossified skull bones, and hypocalcemia; the younger child died during a tonic convulsion, and the older had neonatal hypoparathyroidism. That family provided evidence for an autosomal recessive variant of the syndrome.
A 2023 systematic review of genetically confirmed cases, covering 205 patients from 26 papers for KCS1 and 16 for KCS2, found substantial phenotypic overlap between the two types. Postnatal growth retardation occurred in 52/52 KCS1 and 23/23 KCS2 patients. Low parathyroid hormone levels were seen in 121/121 KCS1 and 16/20 KCS2 patients. Electrolyte disturbances were present in 139/139 KCS1 and 24/27 KCS2 patients. Dental abnormalities occurred in 47/50 KCS1 and 15/16 KCS2 patients, ocular abnormalities in 57/60 KCS1 and 22/23 KCS2 patients, and seizures or spasms in 103/115 KCS1 and 13/16 KCS2 patients.
The review identified distinguishing features. Intellectual disability was far more prevalent in KCS1 (74/80) than in KCS2 (5/24). Conversely, bone cortical thickening was more common in KCS2 (16/20) than in KCS1 (1/18), and medullary stenosis was more frequent in KCS2 (27/28) than in KCS1 (7/46). In the authors' own KCS2 cohort of ten patients from seven families, three had intellectual disability and six had chronic kidney disease, which they established as a new feature of KCS2 not previously considered common.
What is still missing are prospective natural history studies that could clarify the full spectrum of chronic kidney disease in KCS2, and any clinical trials testing interventions for the hypoparathyroidism, growth failure, or bone abnormalities. No drug treatment is mentioned in any of these abstracts. The evidence base remains limited to case series and retrospective reviews, with no data on disease-modifying therapies or long-term outcomes beyond childhood.
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 · 1992 · 62 citations
Kenny–Caffey syndrome in two sibs born to consanguineous parents: Evidence for an autosomal recessive variant
AbstractWe report on 2 sibs with manifestations of the Kenny-Caffey syndrome born to normal, consanguineous parents. Clinical manifestations included dwarfism, internal cortical thickening and medullary stenosis of tubular bones, poorly ossified skull bones, and hypocalcemia. The younger of the two died during a tonic convulsion. The older had neonatal hypoparathyroidism and is now a short intelligent, 1-year-old child. This family gives new support to the existence of an autosomal recessive variant of the syndrome.
The Journal of Clinical Endocrinology & Metabolism · 2023 · 16 citations · open access
Expanding the Phenotypic Spectrum of Kenny–Caffey Syndrome
AbstractCONTEXT: Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish. OBJECTIVE: The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders. METHODS: We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers. RESULTS: Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common. CONCLUSION: Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
INDIGO (University of Illinois at Chicago) · 2023 · 1 citations · open access
Supplementary material for "Expanding the phenotypic spectrum of Kenny-Caffey syndrome: a case series and systematic literature review."
Abstract<strong>ABSTRACT</strong> <strong>Context - </strong>Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in <em>TBCE</em> and <em>FAM111A</em>, respectively. Clinically the phenotypes are difficult to distinguish. <strong>Objective - </strong>The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate on complications that may arise in these disorders. <strong>Design - </strong>We clinically and genetically analyzed ten KCS2 patients from seven families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by three researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by two independent researchers. <strong>Results - </strong>Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low PTH levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23) and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common. <strong>Conclusions - </strong>Our case series established chronic kidney disease as a new feature of KCS2. In literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Supplementary material for "Expanding the phenotypic spectrum of Kenny-Caffey syndrome: a case series and systematic literature review."
Abstract<strong>ABSTRACT</strong> <strong>Context - </strong>Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in <em>TBCE</em> and <em>FAM111A</em>, respectively. Clinically the phenotypes are difficult to distinguish. <strong>Objective - </strong>The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate on complications that may arise in these disorders. <strong>Design - </strong>We clinically and genetically analyzed ten KCS2 patients from seven families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by three researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by two independent researchers. <strong>Results - </strong>Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low PTH levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23) and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common. <strong>Conclusions - </strong>Our case series established chronic kidney disease as a new feature of KCS2. In literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
AbstractAn autosomal recessive form of Kenny-Caffey syndrome that is secondary to mutation(s) in the T CBE gene that encodes tubulin-specific chaperone E; it is characterized by the following: hypoparathyroidism with hypocalcemia, marked growth retardation, craniofacial anomalies, absent diploic space, cortical thickening and medullary stenosis of long bones, and small hands and feet.
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.
