101. Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS):new insights from the fetal perspective
- Author
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Cuinat, Silvestre, Quélin, Chloé, Effray, Claire, Dubourg, Christèle, Le Bouar, Gwenaelle, Cabaret-Dufour, Anne-Sophie, Loget, Philippe, Proisy, Maia, Sauvestre, Fanny, Sarreau, Mélie, Martin-Berenguer, Sophie, Beneteau, Claire, Naudion, Sophie, Michaud, Vincent, Arveiler, Benoit, Trimouille, Aurélien, Macé, Pierre, Sigaudy, Sabine, Glazunova, Olga, Torrents, Julia, Raymond, Laure, Saint-Frison, Marie-Hélène, Attié-Bitach, Tania, Lefebvre, Mathilde, Capri, Yline, Bourgon, Nicolas, Thauvin-Robinet, Christel, Tran Mau-Them, Frédéric, Bruel, Ange-Line, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Faivre, Laurence, Brehin, Anne-Claire, Goldenberg, Alice, Patrier-Sallebert, Sophie, Perani, Alexandre, Dauriat, Benjamin, Bourthoumieu, Sylvie, Yardin, Catherine, Marquet, Valentine, Barnique, Marion, Fiorenza-Gasq, Maryse, Marey, Isabelle, Tournadre, Danielle, Doumit, Raïa, Nugues, Frédérique, Barakat, Tahsin Stefan, Bustos, Francisco, Jaillard, Sylvie, Launay, Erika, Pasquier, Laurent, Odent, Sylvie, Cuinat, Silvestre, Quélin, Chloé, Effray, Claire, Dubourg, Christèle, Le Bouar, Gwenaelle, Cabaret-Dufour, Anne-Sophie, Loget, Philippe, Proisy, Maia, Sauvestre, Fanny, Sarreau, Mélie, Martin-Berenguer, Sophie, Beneteau, Claire, Naudion, Sophie, Michaud, Vincent, Arveiler, Benoit, Trimouille, Aurélien, Macé, Pierre, Sigaudy, Sabine, Glazunova, Olga, Torrents, Julia, Raymond, Laure, Saint-Frison, Marie-Hélène, Attié-Bitach, Tania, Lefebvre, Mathilde, Capri, Yline, Bourgon, Nicolas, Thauvin-Robinet, Christel, Tran Mau-Them, Frédéric, Bruel, Ange-Line, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Faivre, Laurence, Brehin, Anne-Claire, Goldenberg, Alice, Patrier-Sallebert, Sophie, Perani, Alexandre, Dauriat, Benjamin, Bourthoumieu, Sylvie, Yardin, Catherine, Marquet, Valentine, Barnique, Marion, Fiorenza-Gasq, Maryse, Marey, Isabelle, Tournadre, Danielle, Doumit, Raïa, Nugues, Frédérique, Barakat, Tahsin Stefan, Bustos, Francisco, Jaillard, Sylvie, Launay, Erika, Pasquier, Laurent, and Odent, Sylvie
- Abstract
INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.
- Published
- 2024