Abstract
Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.
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Acknowledgements
We are deeply grateful to the patients and their parents for their participation in this study. We thank Philip Bastable from the ‘Pôle Recherche’ of Dijon University Hospital for helpful review of this article. We thank the Regional Council of Burgundy for their financial support of the project.
Authors contributions
Recruitment and Phenotyping was done by Salima El Chehadeh-Djebbar, Edward Blair, Muriel Holder-Espinasse, Anne Moncla, Anne-Marie Frances, Marlène Rio, François-Guillaume Debray, Patrick Rump, Alice Masurel-Paulet, Frédéric Huet, Christel Thauvin-Robinet, Laurence Faivre. Experimental analysis: Nadège Gigot, Patrick Callier, Laurence Duplomb, Bernard Aral.
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Our lab is the reference centre for Cohen syndrome molecular diagnosis in France as we are alone in testing VPS13B gene, giving us some know-how in this field and leading to several publications and research projects.
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El Chehadeh-Djebbar, S., Blair, E., Holder-Espinasse, M. et al. Changing facial phenotype in Cohen syndrome: towards clues for an earlier diagnosis. Eur J Hum Genet 21, 736–742 (2013). https://doi.org/10.1038/ejhg.2012.251
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DOI: https://doi.org/10.1038/ejhg.2012.251
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