{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T16:13:04Z","timestamp":1781194384677,"version":"3.54.1"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p\u201022q11.21. CES is classically defined by association of iris coloboma, anal atresia, and preauricular tags or pits, with high clinical and genetic heterogeneity. We conducted an international retrospective study of patients carrying genomic gain in the 22q11.21 chromosomal region upstream from LCR22\u2010A identified using FISH, MLPA, and\/or array\u2010CGH. We report a cohort of 43 CES cases. We highlight that the clinical triad represents no more than 50% of cases. However, only 16% of CES patients presented with the three signs of the triad and 9% not present any of these three signs. We also highlight the importance of other impairments: cardiac anomalies are one of the major signs of CES (51% of cases), and high frequency of intellectual disability (47%). Ocular motility defects (45%), abdominal malformations (44%), ophthalmologic malformations (35%), and genitourinary tract defects (32%) are other frequent clinical features. We observed that sSMC is the most frequent chromosomal anomaly (91%) and we highlight the high prevalence of mosaic cases (40%) and the unexpectedly high prevalence of parental transmission of sSMC (23%). Most often, the transmitting parent has mild or absent features and carries the mosaic marker at a very low rate (&lt;10%). These data allow us to better delineate the clinical phenotype associated with CES, which must be taken into account in the cytogenetic testing for this syndrome. These findings draw attention to the need for genetic counseling and the risk of recurrence.<\/jats:p>","DOI":"10.1002\/ajmg.a.63476","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T08:36:39Z","timestamp":1700210199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-6830","authenticated-orcid":false,"given":"Guillaume","family":"Jedraszak","sequence":"first","affiliation":[{"name":"Constitutional Genetics Laboratory University Hospital of Amiens  Amiens France"},{"name":"UR4666 University of Picardy Jules Verne  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-8224","authenticated-orcid":false,"given":"Florence","family":"Jobic","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Amiens  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Receveur","sequence":"additional","affiliation":[{"name":"Constitutional Genetics Laboratory University Hospital of Amiens  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Bilan","sequence":"additional","affiliation":[{"name":"Genetics Laboratory University Hospital of Poitiers  Poitiers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7182-9914","authenticated-orcid":false,"given":"Brigitte","family":"Gilbert\u2010Dussardier","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit University Hospital of Poitiers  Poitiers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-1979","authenticated-orcid":false,"given":"Busa","family":"Tiffany","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit University Hospital of Marseille  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Missirian","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Marseille  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-0935","authenticated-orcid":false,"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory University Hospital of Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Odent","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit University Hospital of Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josette","family":"Lucas","sequence":"additional","affiliation":[{"name":"Genetics Laboratory University Hospital of Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christele","family":"Dubourg","sequence":"additional","affiliation":[{"name":"Molecular &amp; Genomic Institute  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Scheidecker","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory &amp; INSERM U1112  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lespinasse","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Hospital of Chamb\u00e9ry  Chamb\u00e9ry France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Goldenberg","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Rouen  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Guerrot","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Rouen  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Joly\u2010Helas","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Rouen  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Chambon","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Rouen  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Le Caignec","sequence":"additional","affiliation":[{"name":"Medical Gentics Unit University Hospital of Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"David","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Grenoble &amp; INSERM U1209 Institute for Advanced Biosciences, University of Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Satre","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Grenoble &amp; INSERM U1209 Institute for Advanced Biosciences, University of Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Vieville","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Grenoble  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Amblard","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Grenoble  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Harbuz","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Grenoble  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-2849","authenticated-orcid":false,"given":"Damien","family":"Sanlaville","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Lyon  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Till","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory University Hospital of Lyon  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Vincent\u2010Delorme","sequence":"additional","affiliation":[{"name":"Catherine Vincent Delorme, Clinical Genetics Unit Guy Fontaine University Hospital of Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Colson","sequence":"additional","affiliation":[{"name":"Catherine Vincent Delorme, Clinical Genetics Unit Guy Fontaine University Hospital of Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Andrieux","sequence":"additional","affiliation":[{"name":"Molecular Genetics Institute University hospital of Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Naudion","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9rome","family":"Toutain","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Rooryck","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory University Hospital of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"de Fr\u00e9minville","sequence":"additional","affiliation":[{"name":"Genetics Laboratory University Hospital of Saint\u2010Etienne  Saint\u2010Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Prieur","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit University Hospital of Saint\u2010Etienne  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie Cormier","family":"Daire","sequence":"additional","affiliation":[{"name":"Medical Genetics Federation Necker\u2010Children's Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Amram","sequence":"additional","affiliation":[{"name":"Clinicial Genetics Unit University Hospital of Creteil  Creteil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Kleinfinger","sequence":"additional","affiliation":[{"name":"Cerba Laboratory  Saint\u2010Ouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Raabe\u2010Meyer","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr Humangenetik Dr. Schulze  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Courage","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Lemke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice G.","family":"Stefanou","sequence":"additional","affiliation":[{"name":"Cytogenetics Unit, Laboratory of Medical Genetics University General Hospital of Patras  Patras Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomaidis","family":"Loretta","sequence":"additional","affiliation":[{"name":"Developmental Assessment Unit National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolakos","family":"Emmanouil","sequence":"additional","affiliation":[{"name":"ATG Genetic Center  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Kitsiou","family":"Tzeli","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henryka","family":"Sodowska","sequence":"additional","affiliation":[{"name":"Niepubliczny Zak\u0142ad Opieki Zdrowotne \u201cGenom\u201d  Ruda Slaska Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasen","family":"Anderson","sequence":"additional","affiliation":[{"name":"Cytogenetics Department Sullivan and Nicolaides Pathology  Taringa Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adayapalam","family":"Nandini","sequence":"additional","affiliation":[{"name":"Department of Cytogenetics Royal Brisbane and Women's Hospital  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Copin","sequence":"additional","affiliation":[{"name":"Constitutional Genetics Laboratory University Hospital of Amiens  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Gar\u00e7on","sequence":"additional","affiliation":[{"name":"Constitutional Genetics Laboratory University Hospital of Amiens  Amiens France"},{"name":"UR4666 University of Picardy Jules Verne  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Liehr","sequence":"additional","affiliation":[{"name":"Jena University Hospital Friedrich Schiller University, Institute of Human Genetics  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-6218","authenticated-orcid":false,"given":"Gilles","family":"Morin","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit University Hospital of Amiens  Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32392"},{"issue":"1","key":"e_1_2_7_3_1","first-page":"23","article-title":"Phenotypic variability of cat\u2010eye syndrome","volume":"12","author":"Berends M. J.","year":"2001","journal-title":"Genet Couns"},{"issue":"6","key":"e_1_2_7_4_1","article-title":"Cat\u2010eye syndrome: A report of two cases and literature review","volume":"14","author":"Gaspar N. S.","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2015.02.002"},{"issue":"1","key":"e_1_2_7_6_1","first-page":"19","article-title":"Partial trisomy due to a de novo duplication 22q11.1\u201022q13.1: A cat\u2010eye syndrome variant with brain anomalies","volume":"21","author":"Karcaaltincaba D.","year":"2010","journal-title":"Genet Couns"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S127481"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.43"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35311"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200607000-00011"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5223.1989.tb00369.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000015035"},{"issue":"3","key":"e_1_2_7_13_1","first-page":"667","article-title":"Minute supernumerary ring chromosome 22 associated with cat eye syndrome: Further delineation of the critical region","volume":"57","author":"Mears A. J.","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.07.031"},{"issue":"3","key":"e_1_2_7_15_1","first-page":"273","article-title":"Phenotypic variability of the cat eye syndrome. Case report and review of the literature","volume":"12","author":"Rosias P. R.","year":"2001","journal-title":"Genet Couns"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(65)92415-3"},{"issue":"1","key":"e_1_2_7_17_1","first-page":"170","article-title":"Congenital hypopituitarism and multiple midline defects in a newborn with non\u2010familial cat eye syndrome. Ital","volume":"48","author":"Serra G.","year":"2022","journal-title":"The Journal of Pediatrics"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320490114"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1701020"}],"updated-by":[{"DOI":"10.1002\/ajmg.a.63807","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000}}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T05:38:42Z","timestamp":1719553122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,16]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/ajmg.a.63476"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63476","archive":["Portico"],"relation":{"erratum":[{"id-type":"doi","id":"10.1002\/ajmg.a.63807","asserted-by":"object"}]},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,16]]},"assertion":[{"value":"2023-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63476"}}