Acrodysostosis 1 (ACRDYS1)

(OMIM phenotype number #101800)

Acrodysostosis comprises a heterogeneous group of rare skeletal dysplasia that share characteristic features, such as severe brachydactyly, facial dysostosis and nasal hypoplasia. Moreover, various degrees of intellectual disability and/or behavioral disorders have also been described in patients affected by Acrodysostosis. This disease include two types caused by two distinct genes, those coding for the type 1 regulatory subunit of cAMP-dependent protein kinase alpha (PRKAR1A) or the cAMP-specific phospho-diesterase 4D (PDE4D). Both of these proteins are important components in the (G-protein-coupled receptors) GPCR-Gsa-cAMP-protein kinase A signaling pathway. These mutations have a different impact in different tissues, explaining the phenotypic heterogeneity, in particular the presence or absence of hormonal resistance. Currently, less than 80 cases have been reported in the literature to date. ACRDYS1 is caused by heterozygous mutation in the PRKAR1A gene and is characterized by short stature, severe brachydactyly, facial dysostosis, nasal hypoplasia,  advanced bone age, obesity and multiple hormone resistance.

Diagnosis is based on the clinical, biochemical and radiological characteristics. Differential diagnosis includes: brachydactyly type E, pseudohypoparathyroidism 1a or pseudopseudohypoparathyroidism.

Treatment: No specific treatment for acrodysostosis exist, up to date. Nevertheless, hormonal resistances, in particular to PTH and TSH, can be treated appropriately as in any other form of hypoparathyroidism and hypothyroidism. At last, dietary and lifestyle measures are recommended to prevent obesity.


PRKAR1A gene, 17q24.2 (OMIM gene/locus number #188830).


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.


Fig. Photographs and X rays of the face and hand of a 12-year-old patient affected with ACRDYS1 resulting from the R368X mutation in PRKAR1A. (a) Side and (b) front photographs of the face. Note the facial dysostosis and severe maxilla-nasal hypoplasia. Photograph (c) and radiograph (d) of the left hand. Note the shortening of all metacarpals and phalanges, and the bulky and stocky aspect of all the affected bones. Standard X-rays show the short and broad metacarpals and phalanges, the cone-shaped epiphyses and advanced carpal and tarsal maturation.

Reproduced by permission from Macmillan Publishers Ltd: Bonekey Rep, Nov 21;1:225, copyright 2012.


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