{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:38:16Z","timestamp":1790030296460,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013123","name":"Fondation de la recherche en sant\u00e9 du Nouveau-Brunswick","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013123","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cyclin\u2010dependent kinase 8 (CDK8) is part of a regulatory kinase module that regulates the activity of the Mediator complex. The Mediator, a large conformationally flexible protein complex, goes on to regulate RNA polymerase II activity, consequently affecting transcriptional regulation. Thus, inactivating mutations of the genes within the kinase module cause aberrant transcriptional regulation and disease, namely, <jats:italic>CDK8<\/jats:italic>\u2010related intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>We describe, for the first time, a likely pathogenic heterozygous <jats:italic>CDK8<\/jats:italic> variant c.599G&gt;A, p.(Arg200Gln) inherited from the biological mother. The clinical presentation of the child and mother is within the described clinical spectrum for IDDHBA; however, undocumented progressive contractures of the hips and knees as well as scoliosis were also observed in the child. This phenotype was not found in the mother, highlighting a heterogenous presentation for the same variant within the same family. Furthermore, the described clinical presentation may further support the notion of a module\u2010 or Mediator\u2010related syndrome with varying clinical presentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case report documents the first inherited case of IDDHBA and expands the phenotypic spectrum for <jats:italic>CDK8<\/jats:italic>\u2010related disease to include undocumented progressive contractures of the hips and knees as well as scoliosis, which may support the notion of a module\u2010 or Mediator\u2010related syndrome with varying clinical presentation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.63537","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T12:15:07Z","timestamp":1704802507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expanding the phenotypic spectrum for <i>CDK8<\/i>\u2010related disease: A case 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