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
Guillaume Jedraszak, Florence Jobic, Aline Receveur, Frédéric Bilan, Brigitte Gilbert‐Dussardier, Tiffany Busa, Chantal Missirian, Marjolaine Willems, Sylvie Odent, Josette Lucas, Christèle Dubourg, Élise Schaefer, Sophie Scheidecker, James Lespinasse, Alice Goldenberg, Anne‐Marie Guerrot, Géraldine Joly‐Hélas, Pascal Chambon, Cédric Le Caignec, Albert David, Charles Coutton, Véronique Satre, Gaëlle Vieville, Florence Amblard, Radu Harbuz, Damien Sanlaville, Marianne Till, Catherine Vincent‐Delorme, Cindy Colson, Joris Andrieux, Sophie Naudion, Jérôme Toutain, Caroline Rooryck, Bénédicte de Fréminville, Fabienne Prieur, Valérie Cormier‐Daire, Daniel Amram, Pascale Kleinfinger, Gisela Raabe‐Meyer, Carolina Courage, Johannes R. Lemke, Eunice G. Stefanou, Thomaidis Loretta, Manolakos Emmanouil, S. Kitsiou Tzeli, Henryka Sodowska, Jasen Anderson, Adayapalam Nandini, Henri Copin, Loïc Garçon, Thomas Liehr, G Morin
Abstract
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-22q11.21. 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-A identified using FISH, MLPA, and/or array-CGH. 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 (<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.