title: Changing facial phenotype in Cohen syndrome: towards clues for an earlier diagnosis.
abstract: Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU de Dijon, France.
authors.forename: Salima
authors.initials: S
authors.lastname: El Chehadeh-Djebbar
authors.forename: Edward
authors.initials: E
authors.lastname: Blair
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Frances
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: François-Guillaume
authors.initials: FG
authors.lastname: Debray
authors.forename: Patrick
authors.initials: P
authors.lastname: Rump
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: Nadège
authors.initials: N
authors.lastname: Gigot
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Laurence
authors.initials: L
authors.lastname: Duplomb
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000015:Abnormalities, Multiple; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D042241:Early Diagnosis; D005145:Face / Q000503:physiopathology*; D005260:Female; D005385:Fingers / Q000002:abnormalities / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009123:Muscle Hypotonia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D009216:Myopia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009765:Obesity / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012162:Retinal Degeneration; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins