title: An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 (GLIS3).
abstract: Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico-medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI-similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Paediatric Endocrinology, Sheffield Children's NHS Foundation Trust, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Dimitri
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, United Kingdom.
authors.forename: Elisa
authors.initials: E
authors.lastname: De Franco
authors.affiliation: Paediatric Department, Prince Mohamed Bin Abdulaziz Hospital, NGHA, Al-Madina, NGHA, Kingdom of Saudi Arabia.
authors.forename: Abdelhadi M
authors.initials: AM
authors.lastname: Habeb
authors.affiliation: Ankara Pediatric Hematology Oncology Education and Training Hospital, Ankara, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Gurbuz
authors.affiliation: Paediatric Department, Maternity and Children Hospital, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Khairya
authors.initials: K
authors.lastname: Moussa
authors.affiliation: Division of Pediatric Endocrinology, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan.
authors.forename: Doris
authors.initials: D
authors.lastname: Taha
authors.affiliation: Department of Paediatric Endocrinology and Diabetes, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia.
authors.forename: Jerry K H
authors.initials: JK
authors.lastname: Wales
authors.affiliation: Department of Paediatrics, Madigan Army Medical Center, Tacoma, Washington.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hogue
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California.
authors.forename: Anne
authors.initials: A
authors.lastname: Slavotinek
authors.affiliation: Department of Paediatrics, Nevill Hall Hospital, Abergavenny, Wales, United Kingdom.
authors.forename: Ambika
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, United Kingdom.
authors.forename: Meena
authors.initials: M
authors.lastname: Balasubramanian
mesh_terms: D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000503:physiopathology; D004268:DNA-Binding Proteins; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology; D005145:Face / Q000503:physiopathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000503:physiopathology; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C512851:GLIS3 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors
keywords: GLIS3; facial dysmorphism; hypothyroidism; neonatal diabetes; phenotype