{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:04:00Z","timestamp":1786122240428,"version":"build-2736575974"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>\n                    This report describes the diagnostic and treatment course of an adult woman with the ultra-rare Au-Kline syndrome (AUKS). Since the age of 32 years, when the syndrome was yet undiagnosed, the patient suffered from behavioral decline coinciding with changes in living conditions. At the age of 38, following a bladder infection, she presented with a delirium for which antipsychotic medication was started. The delirium resolved but, while the medication was continued, the pre-existing behavioral symptoms persisted. Clinicpal genetic evaluation revealed a history of congenital hypotonia, developmental delay, and multiple (craniofacial) dysmorphisms. Subsequent trio-based genetic testing demonstrated a novel pathogenic variant in the\n                    <jats:italic>HNRNPK<\/jats:italic>\n                    gene, causative for AUKS. Clinical neuropsychological assessment showed moderate intellectual disability, slow information processing speed, restricted verbal expression, and limited comprehension. Registration of sensory information was severely hampered and there was difficulty in self-modulating the sensory information to be processed. Contextual adaptations and individual psychomotor therapy were then implemented to optimize sensory and motor information processing, to promote daily functioning, and reduce behavioral decline. These interventions, along with the long-term psychotropic medication, had beneficial effects on her functioning, which subsequently returned to near premorbid levels by the age of 45. Overall, this case underscores that the genetic and neuropsychological identification of a neurodevelopmental disorder, together with the integration of tailored psychomotor interventions and contextual adaptations, can improve psychiatric management and daily functioning, and mitigate behavioral decline in adulthood, even following a prolonged diagnostic delay.\n                  <\/jats:p>","DOI":"10.3389\/fpsyt.2026.1864501","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:02:15Z","timestamp":1786093335000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: A novel HNRNPK gene variant causing Au-Kline syndrome; the genotype and phenotype of the oldest individual ever described"],"prefix":"10.3389","volume":"17","author":[{"given":"Anja G.","family":"Bos-Roubos","sequence":"first","affiliation":[{"name":"Center of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry","place":["Venray, Netherlands"]},{"name":"Donders Institute for Brain, Cognition, and Behaviour, Radboud University","place":["Nijmegen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"te Brinke","sequence":"additional","affiliation":[{"name":"Center of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry","place":["Venray, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A.","family":"Kattentidt-Mouravieva","sequence":"additional","affiliation":[{"name":"Stichting Zuidwester","place":["Middelharnis, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolph","family":"Pfundt","sequence":"additional","affiliation":[{"name":"Human Genetics, Radboud University Medical Center","place":["Nijmegen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.G.","family":"de Graaff","sequence":"additional","affiliation":[{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Erasmus University Medical Center","place":["Rotterdam, Netherlands"]},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Radboud University Medical Center","place":["Nijmegen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Wingberm\u00fchle","sequence":"additional","affiliation":[{"name":"Center of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry","place":["Venray, Netherlands"]},{"name":"Donders Institute for Brain, Cognition, and Behaviour, Radboud University","place":["Nijmegen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos I.M.","family":"Egger","sequence":"additional","affiliation":[{"name":"Center of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry","place":["Venray, Netherlands"]},{"name":"Donders Institute for Brain, Cognition, and Behaviour, Radboud University","place":["Nijmegen, Netherlands"]},{"name":"Stevig Specialized and Forensic Care for People with Intellectual Disabilities","place":["Dichterbij, Oostrum, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","article-title":"Au-Kline syndrome","volume-title":"GeneReviews\u00ae [Internet]","author":"Au","year":"2019"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2025.07.001","article-title":"An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome","volume":"109","author":"Choufani","year":"2022","journal-title":"Am J Hum Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22837","article-title":"GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK","volume":"36","author":"Au","year":"2015","journal-title":"Hum Mutat"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8628(19970131)68:3<347::aid-ajmg18>3.3.co;2-6","article-title":"New MCA\/MR syndrome with generalized hypotonia, congenital hydronephrosis, and characteristic face","volume":"68","author":"Okamoto","year":"1997","journal-title":"Am J Med Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.853028","article-title":"Case report: Exome and RNA sequencing identify a novel de novo missense variant in HNRNPK in a Chinese patient with Au-Kline syndrome","volume":"13","author":"Pan","year":"2022","journal-title":"Front Genet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-59914-9_2","article-title":"Phenotypic spectrum of Au-Kline syndrome: a report of six new cases and review of the literature","volume":"26","author":"Au","year":"2018","journal-title":"Eur J Hum Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12119","article-title":"Characteristics and the trajectory of behaviour problems in adults with intellectual disabilities","volume":"59","author":"Deb","year":"2015","journal-title":"J Intellect Disabil Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/dtb.2018.000009","article-title":"Stopping, rationalising or optimising antipsychotic drug treatment in people with intellectual disability and\/or autism","volume":"57","author":"Shankar","year":"2019","journal-title":"Drug Ther Bull"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2009.06.003","article-title":"Intellectual disability and its relationship to autism spectrum disorders","volume":"30","author":"Matson","year":"2009","journal-title":"Res Dev Disabil"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.106.028845","article-title":"Prevalence of dementia in intellectual disability using different diagnostic criteria","volume":"191","author":"Strydom","year":"2007","journal-title":"Br J Psychiatry"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1864501\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:02:18Z","timestamp":1786093338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1864501\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":10,"alternative-id":["10.3389\/fpsyt.2026.1864501"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1864501","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"1864501"}}