Abstract
Au–Kline syndrome (AKS, OMIM 616580) is a multiple malformation syndrome, first reported in 2015, associated with intellectual disability. AKS has been associated with de novo loss-of-function variants in HNRNPK (heterogeneous ribonucleoprotein K), and to date, only four of these patients have been described in the literature. Recently, an additional patient with a missense variant in HNRNPK was also reported. These patients have striking facial dysmorphic features, including long palpebral fissures, ptosis, deeply grooved tongue, broad nose, and down-turned mouth. Patients frequently also have skeletal and connective tissue anomalies, craniosynostosis, congenital heart malformations, and renal anomalies. In this report, we describe six new patients and review the clinical information on all reported AKS patients, further delineating the phenotype of AKS. There are now a total of 9 patients with de novo loss-of-function variants in HNRNPK, one individual with a de novo missense variant in addition to 3 patients with de novo deletions of 9q21.32 that encompass HNRNPK. While there is considerable overlap between AKS and Kabuki syndrome (KS), these additional patients demonstrate that AKS does have a distinct facial gestalt and phenotype that can be differentiated from KS. This growing AKS patient cohort also informs an emerging approach to management and health surveillance for these patients.
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Acknowledgements
We would like to thank the patients and their families for their participation and support. We would also like to acknowledge the help and support of Marina Kerr, Lukas Lange, Alistair Pagnamenta, Jenny Taylor, and David Keays. We would also like to thank Taila Hartley (Clinical Coordinator) and Chandree Beaulieu (Project Manager) at the Children’s Hospital of Eastern Ontario Research Institute for their contribution to the infrastructure of Care4Rare. Finally, we would like to thank Care4Rare Consortium: ‘Enhanced Care for Rare Genetic Diseases in Canada’; Gene Discovery Steering Committee—Kym Boycott (lead; University of Ottawa), Alex MacKenzie (co-lead; University of Ottawa), Jacek Majewski (McGill University), Michael Brudno (University of Toronto), Dennis Bulman (University of Ottawa), David Dyment (University of Ottawa).
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Au, P.Y.B., Goedhart, C., Ferguson, M. et al. Phenotypic spectrum of Au–Kline syndrome: a report of six new cases and review of the literature. Eur J Hum Genet 26, 1272–1281 (2018). https://doi.org/10.1038/s41431-018-0187-2
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DOI: https://doi.org/10.1038/s41431-018-0187-2
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