{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T09:32:43Z","timestamp":1758274363535,"version":"3.41.2"},"reference-count":81,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio\u2010facio\u2010cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2428","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T05:20:40Z","timestamp":1712380840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Autism spectrum disorder profiles in <scp>RASopathies<\/scp>: A\u00a0systematic review"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-8560","authenticated-orcid":false,"given":"Edward","family":"Debbaut","sequence":"first","affiliation":[{"name":"Center for Developmental Psychiatry, Department of Neurosciences KU Leuven  Leuven Belgium"},{"name":"Leuven Autism Research (LAuRes) KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2512-4694","authenticated-orcid":false,"given":"Jean","family":"Steyaert","sequence":"additional","affiliation":[{"name":"Center for Developmental Psychiatry, Department of Neurosciences KU Leuven  Leuven Belgium"},{"name":"Leuven Autism Research (LAuRes) KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouna","family":"El\u00a0Bakkali","sequence":"additional","affiliation":[{"name":"Faculty of Medicine KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102013\u2010101951"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36374"},{"volume-title":"DSM\u2010IV: Diagnostic and statistical manual of mental disorders","year":"1994","author":"American Psychiatric Association","key":"e_1_2_11_4_1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30299"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.175.5.444"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/BJD.17404"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010016\u20102877\u20103"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065\u2010018\u20109380\u2010x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229\u2010021\u201000481\u20103"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010022\u201005571\u20106"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/21622965.2020.1780924"},{"key":"e_1_2_11_14_1","first-page":"4457","volume-title":"Encyclopedia of autism spectrum disorders","author":"Constantino J. N.","year":"2002"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.04.075"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010018\u20103478\u20100"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/DMCN.14725"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010021\u201009414\u2010w"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817\u2010200205000\u201000002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/DMCN.13394"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-1868"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010016\u20109159\u20104"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/DMCN.12043"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010014\u20102321\u20105"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/FPSYT.2020.585700\/BIBTEX"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0000000000000939"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23624"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229\u2010016\u20100072\u20101"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/09297049.2021.1976129"},{"key":"e_1_2_11_30_1","first-page":"1054","article-title":"Multidimensional influences on autism symptom measures: Implications for use in etiological","volume":"55","author":"Havdahl K. A.","year":"2016","journal-title":"Research"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.13388"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10519\u2010010\u20109430\u20105"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/AUR.1474"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20107610.2012.02589.x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010012\u20101719\u20101"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CLINDERMATOL.2020.03.010"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012422"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010020\u201004717\u20100"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62436"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000040"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/AJMG.A.31465"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010022\u201009452\u2010y"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41436\u2010021\u201001170\u20105\/ATTACHMENT\/FC55EA50\u20105CA2\u20104891\u2010BE65\u2010FE6F6C9BADAE\/MMC1.PDF"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/BRAIN.2014.0334"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JAAC.2017.03.013"},{"volume-title":"Autism diagnostic observation schedule","year":"2012","author":"Lord C.","key":"e_1_2_11_46_1"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.852208"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBAMCR.2006.10.001"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14558"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2016.2600"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14653"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005000"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073809359540"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1001\/ARCHNEUR.1988.00520290115023"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15627"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPUROL.2015.06.002"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14071338"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1136\/BMJ.N71"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/DMCN.14517\/ABSTRACT"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689\u2010018\u20109239\u20108"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3189"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32280"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32414"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2013.07.011"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15143612"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049344"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/AJMG.A.40632"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.5195\/JMLA.2021.962"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010738829569"},{"volume-title":"Autism diagnostic interview\u2010revised","year":"2003","author":"Rutter M.","key":"e_1_2_11_70_1"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/AJMG.A.38174"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1365\u20102133.2011.10744.X"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1365\u20102133.2010.10122.X"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13229\u2010018\u20100190\u2010Z\/TABLES\/1"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/HMG\/DDW191"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36549"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/DMCN.12044"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040297"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(90)90252\u2010A"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(07)61602\u2010X"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12038"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38641"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T10:49:24Z","timestamp":1714128564000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":81,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/mgg3.2428"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2428","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2428"}}