Acrodysostosis 2 (ACRDYS2)

(OMIM phenotype number #614613)

Acrodysostosis is a rare skeletal dysplasia, which includes two forms, Acrodysostosis 1 (ACRDYS1) and ACRDYS2, with similar clinical characteristics, such as severe brachydactyly, facial dysostosis and nasal hypoplasia, and different mutations (see also ACRDYS1). ACRDYS2 is caused by heterozygous mutation in the PDE4D gene, encoding cAMP-specific phospho-diesterase 4D. This disease is characterized by brachydactyly, facial dysostosis, spinal stenosis, short stature, often intellectual disability and in some rare cases hormone resistance. The maxillo-nasal hypoplasia with flattening of nasal ridge appears to be more severe in ACRDYS2 patients, and some patients with do not present a short stature than ACRDYS1. See also ACRDYS1.

Gene

PDE4D gene, 5q12 (OMIM gene/locus number #600129).

Phenotype

Form of skeletal dysplasia characterized by brachydactyly, short stature, obesity, facial dysostosis (broad face, widely spaced eyes, maxillo-nasal hypoplasia), small broad hands and feet with stubby digits, except for the big toe, which is enlarged.

Main biochemical alterations

Low or normal Ca and Pi, low or normal PTH, ± multiple hormone resistance (rare).

References

  1. Lee H, Graham JM Jr, Rimoin DL, et al. Exome sequencing identifies PDE4D mutations in acrodysostosis. Am J Hum Genet. 2012 Apr 6;90(4):746-51.
  2. Silve C, Le-Stunff C, Motte E et al. Acrodysostosis syndromes. Bonekey Rep. 2012 Nov 21;1:225.
  3. Silve C, Clauser E, Linglart A. Acrodysostosis. Horm Metab Res. 2012 Sep;44(10):749-58.
  4. Butler MG, Rames LJ, Wadlington WB. Acrodysostosis: report of a 13-year-old boy with review of literature and metacarpophalangeal pattern profile analysis. Am J Med Genet. 1988 Aug;30(4):971-80.
  5. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  6. http://www.omim.org