title: Kabuki syndrome: expanding the phenotype to include microphthalmia and anophthalmia.
abstract: Kabuki syndrome is a rare genetic malformation syndrome that is characterized by distinct facies, structural defects and intellectual disability. Kabuki syndrome may be caused by mutations in one of two histone methyltransferase genes: KMT2D and KDM6A. We describe a male child of nonconsanguineous Irish parents presenting with multiple malformations, including bilateral extreme microphthalmia; cleft palate; congenital diaphragmatic hernia; duplex kidney; as well as facial features of Kabuki syndrome, including interrupted eyebrows and lower lid ectropion. A de-novo germline mutation in KMT2D was identified. Whole-exome sequencing failed to reveal mutations in any of the known microphthalmia/anopthalmia genes. We also identified four other patients with Kabuki syndrome and microphthalmia. We postulate that Kabuki syndrome may produce this type of ocular phenotype as a result of extensive interaction between KMT2D, WAR complex proteins and PAXIP1. Children presenting with microphthalmia/anophthalmia should be examined closely for other signs of Kabuki syndrome, especially at an age where the facial gestalt might be less readily appreciable.
authors.affiliation: aDepartment of Clinical Genetics, Our Lady's Children's Hospital Crumlin, Dublin, Ireland bDepartment of Clinical Genetics, Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester cDepartment of Clinical Genetics, Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Terri P
authors.initials: TP
authors.lastname: McVeigh
authors.forename: Siddharth
authors.initials: S
authors.lastname: Banka
authors.forename: William
authors.initials: W
authors.lastname: Reardon
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000853:Anophthalmos / Q000175:diagnosis* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D006402:Hematologic Diseases / Q000175:diagnosis* / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D008297:Male; D008850:Microphthalmos / Q000175:diagnosis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015837:Vestibular Diseases / Q000175:diagnosis* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C485876:PAXIP1 protein, human; D056466:Histone Demethylases; C523998:KDM6A protein, human