Li Xin Zhang, Gabrielle Lemire, Claudia Gonzaga-Jauregui, Sirinart Molidperee, Carolina Galaz-Montoya, David S Liu, Alain Verloes, Amelle G Shillington, Kosuke Izumi, Alyssa L Ritter, Beth Keena, Elaine Zackai, Dong Li, Elizabeth Bhoj, Jennifer M Tarpinian, Emma Bedoukian, Mary K Kukolich, A Micheil Innes, Grace U Ediae, Sarah L Sawyer, Karippoth Mohandas Nair, Para Chottil Soumya, Kinattinkara R Subbaraman, Frank J Probst, Jennifer A Bassetti, Reid V Sutton, Richard A Gibbs, Chester Brown, Philip M Boone, Ingrid A Holm, Marco Tartaglia, Giovanni Battista Ferrero, Marcello Niceta, Maria Lisa Dentici, Francesca Clementina Radio, Boris Keren, Constance F Wells, Christine Coubes, Annie Laquerrière, Jacqueline Aziza, Charlotte Dubucs, Sheela Nampoothiri, David Mowat, Millan S Patel, Ana Bracho, Francisco Cammarata-Scalisi, Alper Gezdirici, Alberto Fernandez-Jaen, Natalie Hauser, Yuri A Zarate, Katherine A Bosanko, Klaus Dieterich, John C Carey, Jessica X Chong, Deborah A Nickerson, Michael J Bamshad, Brendan H Lee, Xiang-Jiao Yang, James R Lupski, Philippe M Campeau
Journal: Genetics in medicine : official journal of the American College of Medical Genetics 2021;22(8):1338-1347
PMID: 32424177
PURPOSE
Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized.
METHODS
We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum.
RESULTS
We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent.
CONCLUSION
Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.
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