ACRODYSOSTOSIS TYPE 1 (ACRDYS1) AND ACRODYSOSTOSIS TYPE 2 (ACRDYS2)

PRKAR1A AND PDE4D GENE ANALYSIS IN PATIENTS WITH ACRDYS1 AND ACRDYS2

Acrodysostosis type 1 is an autosomal dominant form of skeletal dysplasia characterised by short stature, severe brachydactyly and facial dysostosis.  Individuals often have advanced bone age, may be obese and some are resistant to multiple hormones including parathyroid, calcitonin and growth hormone releasing hormone.

Acrodysostosis type 2 is an autosomal dominant form of skeletal dysplasia characterised by short stature, brachydactyly, facial dysostosis and spinal stenosis. Many patients have intellectual disability and some have hormone resistance.

Disease-causing variants in exon 9 and 11 of the PRKAR1A have been identified in 100% of patients with radiological and clinical features of acrodysostosis type 1 and hormone resistance  (Linglart et al. 2011 N Engl J Med 364:2218-2226; Linglart et al. 2012 J Clin Endocrinol Metab 97:2012-2326 ; Michot et al. 2012 Am J Hum Genet 90:740 -745).  Where patients do not have hormone resistance, 90-100% of patients have PDE4D disease-causing variants Michot et al. 2012 Am J Hum Genet 90:740 -745 and Linglart et al. 2012 J Clin Endocrinol Metab 97:2012-2326. Where hormone resistance was not specifically investigated, exon 11 PRKAR1A variants were found in 40% of patients (remaining 60% having PDE4D variants) Lee et al. 2012 Am J Hum Genet 90:746-751.

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.