title: Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2.
abstract: Acroscyphodysplasia (OMIM250215) is a distinctive form of metaphyseal dysplasia characterized by the distal femoral and proximal tibial epiphyses embedded in cup-shaped, large metaphyses known as metaphyseal scypho ("scypho" = cup) deformity. It is also associated with severe growth retardation and brachydactyly. The underlying molecular mechanism of acroscyphodysplasia has not yet been elucidated, although scypho-deformity of the knee has been reported in three patients with acrodysostosis due to a mutation in the PDE4D gene. We report on the clinical, radiological, and molecular findings of five female patients with acroscyphodysplasia; two were diagnosed as pseudohypoparathyroidism (PHP) or Albright hereditary osteodystropy, and the other three as acrodysostosis. They all had radiological findings consistent with severe metaphyseal scypho-deformity and brachydactyly. Heterozygous mutations were identified in the PHP patients consisting of one novel (p.Q19X) and one recurrent (p.R231C) mutation of the GNAS gene, as well as, in the acrodysostosis patients consisting of two novel mutations (p.T224I and p.I333T) of the PDE4D gene. We conclude that metaphyseal acroscyphodysplasia is a phenotypic variation of PHP or acrodysostosis caused by either a GNAS or PDE4D mutation, respectively.
authors.affiliation: Department of Pediatrics, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Mitsui
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kim
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hall
authors.forename: Amaka
authors.initials: A
authors.lastname: Offiah
authors.forename: Diana
authors.initials: D
authors.lastname: Johnson
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Teck-Hock
authors.initials: TH
authors.lastname: Toh
authors.forename: Shun
authors.initials: S
authors.lastname: Soneda
authors.forename: Dai
authors.initials: D
authors.lastname: Keino
authors.forename: Shohei
authors.initials: S
authors.lastname: Matsubayashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ishii
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000293:Adolescent; D001848:Bone Diseases, Developmental / Q000235:genetics; D059327:Brachydactyly / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics; D004413:Dysostoses / Q000235:genetics*; D004838:Epiphyses / Q000002:abnormalities*; D005097:Exostoses, Multiple Hereditary / Q000235:genetics*; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007717:Knee / Q000002:abnormalities*; D009154:Mutation / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics*; D011547:Pseudohypoparathyroidism / Q000235:genetics*
chemical_list: D002864:Chromogranins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: GNAS; PDE4D; acrodysostosis; acroscyphodysplasia; pseudohypoparathyroidism