title: Long term follow up of two independent patients with Schinzel-Giedion carrying SETBP1 mutations.
abstract: Schinzel-Giedion syndrome (SGS, MIM #269150) is a rare syndrome characterized by severe intellectual disability, typical facial gestalt, hypertrichosis and multiple congenital malformations including skeletal, genitourinary, renal and cardiac abnormalities. The prognosis of SGS is very severe and death occurs generally within a few years after birth. In 2002, we reported 2 children with SGS with a follow-up of 3 years. They presented a very similar and particular phenotype associating distinctive facial gestalt, severe developmental delay, megacalycosis, progressive neurodegeneration, alacrimi, corneal hypoesthesia and deafness. Furthermore, temporal bone imaging revealed a tuning-fork malformation of the stapes. In 2010, Hoischen et al. identified in SGS patients pathogenic heterozygous de novo mutations in SETBP1. We sequenced SETBP1 in our patients and found the previously reported c.2608G>A (p.Gly870Ser) mutation in both children. Since 2002, one of our patients died at 6 years old and the other patient is still alive at 15 years old. Such a life expectancy has never been reported so far. We describe herein the follow up of the 2 children during 6 and 15 years respectively. This article gives further evidence of the implication of SETBP1 as the major gene of SGS, and reports the previously unseen natural evolution of the disease in a 15 years old patient.
authors.affiliation: Laboratoire de Génétique Médicale INSERM U1112, Institut de Génétique Médicale d'Alsace (IGMA), Faculté de Médecine de Strasbourg, Université De Strasbourg, Strasbourg, France; Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Herenger
authors.affiliation: Laboratoire de Génétique Médicale INSERM U1112, Institut de Génétique Médicale d'Alsace (IGMA), Faculté de Médecine de Strasbourg, Université De Strasbourg, Strasbourg, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.affiliation: Laboratoire de Génétique Médicale INSERM U1112, Institut de Génétique Médicale d'Alsace (IGMA), Faculté de Médecine de Strasbourg, Université De Strasbourg, Strasbourg, France; Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Schaefer
authors.affiliation: Laboratoire de Génétique Médicale INSERM U1112, Institut de Génétique Médicale d'Alsace (IGMA), Faculté de Médecine de Strasbourg, Université De Strasbourg, Strasbourg, France; Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Scheidecker
authors.affiliation: Reference Centre for Orodental Manifestations of Rare Diseases, CRMR, Pôle de Médecine et Chirurgie Bucco-Dentaires, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Manière
authors.affiliation: Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pelletier
authors.affiliation: Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Alembik
authors.affiliation: Service de Radiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Christmann
authors.affiliation: Service de Pédiatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Clavert
authors.affiliation: Service de Pédiatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Terzic
authors.affiliation: Service de Pédiatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
authors.affiliation: Service de Pédiatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: De Saint Martin
authors.affiliation: Laboratoire de Génétique Médicale INSERM U1112, Institut de Génétique Médicale d'Alsace (IGMA), Faculté de Médecine de Strasbourg, Université De Strasbourg, Strasbourg, France; Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address: dollfus@unistra.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D001921:Brain / Q000002:abnormalities; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D005500:Follow-Up Studies; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics; D008969:Molecular Sequence Data; D009264:Nails, Malformed / Q000175:diagnosis / Q000235:genetics*; D053040:Nephrolithiasis / Q000175:diagnosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011379:Prognosis; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C425066:SETBP1 protein, human
keywords: Coraliform nephrolithiasis; Dental abnormalities; SETBP1; Schinzel–Giedion syndrome