title: Concurrent occurrence of an inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving MAP2K2 in a patient with developmental delay, distinctive facial features, and lambdoid synostosis.
abstract: A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2), in which mutations cause the cardio-facio-cutaneous (CFC) syndrome. Reports of patients with overlapping 19p13.3 microdeletions of this region describe similar clinical manifestations including distinctive facial features: prominent forehead, horizontal/down-slanting palpebral fissures, long midface, pointed chin/angular jaw, sparse eyebrows, and underdeveloped cheekbones. Some of these findings overlapped to that of the patients with 16p13.11 microduplications and CFC syndrome. Although craniosynostosis was occasionally observed in patients with dominant-negative mutations in RAS/MAP kinase signaling genes (RASopathies) related to CFC syndrome, it was also reported in two patients with 16p13.11 microduplications. Genetic contributions of both chromosomal aberrations were discussed.
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ondo
authors.affiliation: Department of Pediatrics, Minami Kyushu National Hospital, Aira, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Matsufuji
authors.affiliation: Department of Pediatrics, Minami Kyushu National Hospital, Aira, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Sano
authors.affiliation: Department of Pediatrics, Minami Kyushu National Hospital, Aira, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsuru
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Oyoshi
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Nayuta
authors.initials: N
authors.lastname: Higa
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokimura
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D058674:Chromosome Duplication / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003398:Craniosynostoses / Q000235:genetics* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D004476:Ectodermal Dysplasia / Q000235:genetics*; D019066:Facies; D005183:Failure to Thrive / Q000235:genetics*; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D059785:Karyotype; D048370:MAP Kinase Kinase 2 / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: C482128:MAP2K2 protein, human; D048370:MAP Kinase Kinase 2
keywords: 16p13.11 microduplication; 19p13.3 microdeletion; Lambdoid synostosis; MAP2K2