{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:44:43Z","timestamp":1792611883749,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To characterize the neurodevelopmental profile of patients with Phelan\u2013McDermid syndrome (PMS) and describe the nature and trajectory of regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This was a retrospective, monocentric study examining the clinical and developmental data of 24 patients (average age\u00a0=\u00a025\u2009years 6\u2009months, range\u00a0=\u00a06\u201356\u2009years, <jats:italic>n<\/jats:italic>\u00a0=\u00a013 males) with a confirmed 22q13.3 terminal deletion carried out at the Centre for Human Genetics, University Hospital Leuven. The neurodevelopmental profile of individuals with PMS was examined, combining both cross\u2010sectional and longitudinal data obtained by systematic review of digital medical records.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Remarkable loss of skills was present in 19 individuals affecting both language and motor skills. The first manifestations of neurodevelopmental regression occurred, on average, at the age of 7\u2009years 6\u2009months (range\u00a0=\u00a05\u201311\u2009years). Language skills (active vocabulary) were primarily affected followed by, in order of loss, psychosocial adaptability, fine motor skills, and walking ability. The course of regression was characterized by a distinctive four\u2010stage pattern. The first stage often occurred around mid\u2010childhood and was defined by a pronounced and abrupt decline of language skills. This stage was generally followed by the second stage where a (prolonged) period of stagnation of regression was seen. The third stage was defined by acute neuropsychiatric decline (e.g. catatonia, hallucinations, psychosis). Acute events such as severe sickness, hormonal shifts, and psychosocial stress frequently preceded the fourth and final stage, which was characterized by severe neuromotor degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Neurodevelopmental regression should be considered as a key feature of PMS. We present a four\u2010stage model of neurodevelopmental regression, entailing language skills, fine and gross motor function, and psychosocial adaptation, which can be applied in future practice and research.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.15482","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T17:03:50Z","timestamp":1670432630000},"page":"917-925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neurodevelopmental profile and stages of regression in Phelan\u2013<scp>McDermid<\/scp> syndrome"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-3470","authenticated-orcid":false,"given":"Yumi","family":"Dille","sequence":"first","affiliation":[{"name":"Department of Human Genetics University Hospital Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7118-0139","authenticated-orcid":false,"given":"Lieven","family":"Lagae","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration, Section Paediatric Neurology University Hospital Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4258-4537","authenticated-orcid":false,"given":"Ann","family":"Swillen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University Hospital Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1584-5327","authenticated-orcid":false,"given":"Griet Van","family":"Buggenhout","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University Hospital Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334260"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/340363"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-39"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006935"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815600872"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-4-18"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000672"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.038604"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1423-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01592-5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4279-15.2016"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09965"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/073428299801600101"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2004.t01-1-00287.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2584"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00341"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.57"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.05.032"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.12.025"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-019-9273-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2017.03.010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-008-9073-y"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503840"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(200022)97:2<128::AID-AJMG4>3.0.CO;2-Z"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-019-0291-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-020-9309-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-015-0490-1"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2017-220778"}],"container-title":["Developmental Medicine &amp; 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