title: Detailed clinical, genetic and neuroimaging characterization of OFD VI syndrome.
abstract: Oral-facial-digital syndrome type VI (OFD VI) is characterized by the association of malformations of the face, oral cavity and extremities, distinguished from the 12 other OFD syndromes by cerebellar and metacarpal abnormalities. Cerebellar malformations in OFD VI have been described as a molar tooth sign (MTS), thus, including OFD VI among the "Joubert syndrome related disorders" (JSRD). OFD VI diagnostic criteria have recently been suggested: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of hands or feet; 3) hypothalamic hamartoma. In order to further delineate this rare entity, we present the neurological and radiological data of 6 additional OFD VI patients. All patients presented oral malformations, facial dysmorphism and distal abnormalities including frequent polydactyly (66%), as well as neurological symptoms with moderate to severe mental retardation. Contrary to historically reported patients, mesoaxial polydactyly did not appear to be a predominant clinical feature in OFD VI. Sequencing analyzes of the 14 genes implicated in JSRD up to 2011 revealed only an OFD1 frameshift mutation in one female OFD VI patient, strengthening the link between these two oral-facial-digital syndromes and JSRD.
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Grand-Est, Hôpital d'Enfants, CHU Dijon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Darmency-Stamboul
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.forename: Estelle
authors.initials: E
authors.lastname: Lopez
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mejean
authors.forename: John
authors.initials: J
authors.lastname: Dean
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerres
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Bérénice
authors.initials: B
authors.lastname: Doray
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.forename: Matthew
authors.initials: M
authors.lastname: Pastore
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Crenshaw
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Nadège
authors.initials: N
authors.lastname: Gigot
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009154:Mutation; D059906:Neuroimaging; D009958:Orofaciodigital Syndromes / Q000175:diagnosis* / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D014057:Tomography, X-Ray Computed
chemical_list: C115130:OFD1 protein, human; D011506:Proteins