{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:53:17Z","timestamp":1793393597352,"version":"4.5.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neurodevelopmental disorders have a multifactorial etiology, since biological, genetic, psychosocial and environmental risk factors are involved. Recent studies have been linking neurodevelopmental disorders and intellectual disability with a variety of genes, some of which encoding neuronal cell-adhesion molecules. Among these, KIRREL3 is known to play a role in CNS development, and his variants have recently been related to intellectual disability, autism spectrum disorder, childhood apraxia of speech, cerebellar hypoplasia and mild dysmorphic features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      In this study, we describe a young Caucasian boy with mild intellectual disability, cerebellar anomalies (cerebellar hypoplasia and mega cisterna magna) and minor dysmorphic features associated to a novel\n                      <jats:italic>KIRREL3<\/jats:italic>\n                      variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Aim of the present case report is to expand the clinical spectrum of\n                      <jats:italic>KIRREL3<\/jats:italic>\n                      -related diseases towards a milder phenotype than what is already described in the literature. We speculate that the interaction between KIRREL3 and CASK might play a major role in promoting cognitive and cerebellar development, contributing to a variety of clinical manifestations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13052-023-01488-7","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T11:02:54Z","timestamp":1692615774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["KIRREL3-related disorders: a case report confirming the radiological features and expanding the clinical spectrum to a less severe phenotype"],"prefix":"10.1186","volume":"49","author":[{"given":"Andrea","family":"Querzani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-2023","authenticated-orcid":false,"given":"Fabio","family":"Sirchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Rustioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Orsini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luigi","family":"Marseglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Savasta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Chiapparini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Foiadelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"1488_CR1","doi-asserted-by":"crossref","unstructured":"Fleischhacker WW, Brooks D. Neurodevelopmental disorders. Neurodev Disord. 2005;(August):1\u2013141.","DOI":"10.1007\/3-211-31222-6"},{"issue":"6","key":"1488_CR2","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/sj.ejhg.5201595","volume":"14","author":"J Chelly","year":"2006","unstructured":"Chelly J, Khelfaoui M, Francis F, Ch\u00e9rif B, Bienvenu T. Genetics and pathophysiology of mental retardation. Eur J Hum Genet. 2006;14(6):701\u201313.","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"1488_CR3","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.ajhg.2008.10.020","volume":"83","author":"K Bhalla","year":"2008","unstructured":"Bhalla K, Luo Y, Buchan T, et al. Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability. Am J Hum Genet. 2008;83(6):703\u201313.","journal-title":"Am J Hum Genet"},{"key":"1488_CR4","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.bbrc.2021.05.063","volume":"563","author":"T Hisaoka","year":"2021","unstructured":"Hisaoka T, Komori T, Fujimoto K, Kitamura T, Morikawa Y. Comprehensive expression pattern of kin of irregular chiasm-like 3 in the adult mouse brain. Biochem Biophys Res Commun. 2021;563:66\u201372.","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"1488_CR5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1086\/511441","volume":"80","author":"F Laumonnier","year":"2007","unstructured":"Laumonnier F, Cuthbert PC, Grant SGN. The role of neuronal complexes in human X-linked brain diseases. Am J Hum Genet. 2007;80(2):205\u201320.","journal-title":"Am J Hum Genet"},{"issue":"October 2007","key":"1488_CR6","first-page":"339","volume":"346","author":"P Gerke","year":"2006","unstructured":"Gerke P, Benzing T, H\u00f6hne M. Neuronal expression and Interaction with the synaptic protein CASK suggest a role for Neph1 and Neph2 in synaptogenesis. J Comp Neurol. 2006;346(October 2007):339\u201346.","journal-title":"J Comp Neurol"},{"issue":"3","key":"1488_CR7","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.mcn.2011.01.007","volume":"46","author":"K Nishida","year":"2011","unstructured":"Nishida K, Nakayama K, Yoshimura S, Murakami F. Role of Neph2 in pontine nuclei formation in the developing hindbrain. Mol Cell Neurosci. 2011;46(3):662\u201370.","journal-title":"Mol Cell Neurosci"},{"issue":"7","key":"1488_CR8","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1002\/ccr3.1560","volume":"6","author":"S Puvabanditsin","year":"2018","unstructured":"Puvabanditsin S, Chen CW, Botwinick M, Hussein K, Mariduena J, Mehta R. Ventriculomegaly and cerebellar hypoplasia in a neonate with interstitial 11q 24 deletion in Jacobsen syndrome region. Clin Case Reports. 2018;6(7):1268\u201375.","journal-title":"Clin Case Reports"},{"issue":"2","key":"1488_CR9","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1037\/a0031653","volume":"25","author":"MW Watkins","year":"2013","unstructured":"Watkins MW, Smith LG. Long-term stability of the Wechsler Intelligence Scale for Children\u2013Fourth Edition. Psychol Assess. 2013;25(2):477\u201383.","journal-title":"Psychol Assess"},{"issue":"6","key":"1488_CR10","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1055\/s-0041-1725964","volume":"52","author":"C Ciaccio","year":"2021","unstructured":"Ciaccio C, Leonardi E, Polli R, et al. A missense de Novo variant in the CASK -interactor KIRREL3 gene leading to neurodevelopmental disorder with mild cerebellar hypoplasia. Neuropediatrics. 2021;52(6):484\u20138.","journal-title":"Neuropediatrics"},{"issue":"3","key":"1488_CR11","first-page":"358","volume":"127","author":"M Talkowski","year":"2012","unstructured":"Talkowski M, Rosenfeld J, Blumenthal I. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell. 2012;127(3):358\u201366.","journal-title":"Cell"},{"issue":"7","key":"1488_CR12","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1016\/j.cell.2012.11.019","volume":"151","author":"JJ Michaelson","year":"2012","unstructured":"Michaelson JJ, Shi Y, Gujral M, et al. Whole-genome sequencing in Autism identifies hot spots for De Novo Germline Mutation. Cell. 2012;151(7):1431\u201342.","journal-title":"Cell"},{"issue":"28","key":"1488_CR13","doi-asserted-by":"publisher","first-page":"5376","DOI":"10.1523\/JNEUROSCI.3058-19.2020","volume":"40","author":"MR Taylor","year":"2020","unstructured":"Taylor MR, Anne Martin E, Sinnen B, et al. Kirrel3-Mediated synapse formation is attenuated by Disease-Associated missense variants. J Neurosci. 2020;40(28):5376\u201388.","journal-title":"J Neurosci"},{"issue":"2","key":"1488_CR14","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/mgg3.354","volume":"6","author":"L Kalsner","year":"2018","unstructured":"Kalsner L, Twachtman-Bassett J, Tokarski K, et al. Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: findings and implications. Mol Genet Genomic Med. 2018;6(2):171\u201385.","journal-title":"Mol Genet Genomic Med"},{"key":"1488_CR15","doi-asserted-by":"crossref","unstructured":"Leblond CS, Cliquet F, Carton C et al. Both rare and common genetic variants contribute to autism in the Faroe Islands. npj Genomic Med. 2019;4(1).","DOI":"10.1038\/s41525-018-0075-2"},{"issue":"7","key":"1488_CR16","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1038\/s41436-018-0380-2","volume":"21","author":"H Guo","year":"2019","unstructured":"Guo H, Duyzend MH, Coe BP, et al. Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes. Genet Med. 2019;21(7):1611\u201320.","journal-title":"Genet Med"},{"issue":"20","key":"1488_CR17","doi-asserted-by":"publisher","first-page":"E2148","DOI":"10.1212\/WNL.0000000000009441","volume":"94","author":"MS Hildebrand","year":"2020","unstructured":"Hildebrand MS, Jackson VE, Scerri TS, et al. Severe childhood speech disorder: gene discovery highlights transcriptional dysregulation. Neurology. 2020;94(20):E2148\u201367.","journal-title":"Neurology"},{"issue":"9","key":"1488_CR18","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/ng.194","volume":"40","author":"J Najm","year":"2008","unstructured":"Najm J, Horn D, Wimplinger I, et al. Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet. 2008;40(9):1065\u20137.","journal-title":"Nat Genet"},{"issue":"12","key":"1488_CR19","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1093\/brain\/awp247","volume":"132","author":"AJ Barkovich","year":"2009","unstructured":"Barkovich AJ, Millen KJ, Dobyns WB. A developmental and genetic classification for midbrain-hindbrain malformations. Brain. 2009;132(12):3199\u2013230.","journal-title":"Brain"}],"container-title":["Italian Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-023-01488-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13052-023-01488-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-023-01488-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T18:38:49Z","timestamp":1700505529000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijponline.biomedcentral.com\/articles\/10.1186\/s13052-023-01488-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,21]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1488"],"URL":"https:\/\/doi.org\/10.1186\/s13052-023-01488-7","relation":{},"ISSN":["1824-7288"],"issn-type":[{"value":"1824-7288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,21]]},"assertion":[{"value":"2 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The parents of the patient agreed and signed an informed consent for publication of clinical data and pictures.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interest"}}],"article-number":"99"}}