title: Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome).
abstract: Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, -1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29-70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith-Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name 'Kagami-Ogata syndrome' for UPD(14)pat and related conditions.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kagami
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.affiliation: Department of Radiology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyazaki
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.affiliation: Department of Pathology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000235:genetics / Q000503:physiopathology; D005260:Female; D018392:Genomic Imprinting; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D011247:Pregnancy; D024182:Uniparental Disomy / Q000235:genetics* / Q000503:physiopathology; D000096803:Imprinting Disorders