Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2

Toshikatsu Mitsui, Ok Hwa Kim, Christine M. Hall, Amaka Offiah, Diana Johnson, Dong Kyu Jin, Teck Hock Toh, Shun Soneda, Dai Keino, Shohei Matsubayashi, Tomohiro Ishii, Gen Nishimura, Tomonobu Hasegawa

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Acroscyphodysplasia (OMIM250215) is a distinctive form of metaphyseal dysplasia characterized by the distal femoral and proximal tibial epiphyses embedded in cup-shaped, largemetaphyses 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 patientswith acrodysostosis due to amutation inthePDE4Dgene. 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 thePDE4Dgene. We conclude that metaphyseal acroscyphodysplasia is a phenotypic variation of PHP or acrodysostosis caused by either a GNAS or PDE4D mutation, respectively.

Original languageEnglish
Pages (from-to)2529-2534
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number10
DOIs
Publication statusPublished - 2014 Oct

Keywords

  • Acrodysostosis
  • Acroscyphodysplasia
  • GNAS
  • PDE4D
  • Pseudohypoparathyroidism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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