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J Hum Genet. 2017 Aug;62(8):741-746. doi: 10.1038/jhg.2017.24. Epub 2017 Mar 2.

ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin-Siris-like syndrome.

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Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Japan.
Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Victorian Clinical Genetics Service, Murdoch Children's Research Institute, Melbourne, Australia.
Department of Pediatrics, Yodogawa Christian Hospital, Osaka City, Osaka, Japan.
Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
Department of Biochemistry, Hamamatsu University School of Medicine, Shizuoka, Japan.


KBG syndrome (KBGS) is an autosomal dominant multiple congenital anomaly-intellectual disability syndrome, characterized by developmental delay with neurological involvements, macrodontia of the upper central incisors, characteristic facial dysmorphism and skeletal anomalies. Variants in ANKRD11 cause KBGS. We present five individuals from four families with ANKRD11 variants identified by whole-exome sequencing. Four of the five were clinically affected, and their diagnoses were varied. One was typical KBGS, two were Coffin-Siris syndrome-like (CSS), and one was intellectual disability with infantile spasms. One individual showed extremely mild phenotype. All individuals fulfilled the proposed diagnostic criteria for KBGS. Phenotypic features overlap between KBGS and CSS to some extent, and characteristic dental and fifth finger/toe findings can indicate differential diagnosis. These findings indicate that patients with ANKRD11 variants occupy a wide spectrum of intellectual disability, including clinically normal individuals. This is the first report highlighting the clinical overlap between KBGS and CSS and supporting the recently proposed clinical concept, in which transcriptional machineries are disrupted.

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