Acrodysostosis

Acrodysostosis is a rare skeletal dysplasia characterized by severe brachydactyly (abnormally short hands and feet) with cone-shaped epiphyses, facial dysostosis (midface hypoplasia with a small, upturned nose and flat nasal bridge), and short stature. The condition affects multiple body systems, most notably the skeletal system, but also the endocrine and neurological systems. Facial features typically include a flattened midface, a broad and rounded nose with a depressed nasal bridge, and prognathism (protruding jaw). Advanced bone age is a hallmark radiographic finding. Two genetic subtypes have been identified: Acrodysostosis type 1 (ACRDYS1, also known as acrodysostosis with hormonal resistance), caused by mutations in the PRKAR1A gene, is associated with resistance to multiple hormones including parathyroid hormone (PTH) and thyroid-stimulating hormone (TSH), and frequently involves intellectual disability. Acrodysostosis type 2 (ACRDYS2), caused by mutations in the PDE4D gene, typically presents without hormonal resistance but may also be associated with intellectual disability, though often milder. There is no cure for acrodysostosis. Management is supportive and multidisciplinary, focusing on monitoring and treating hormonal abnormalities (such as hypothyroidism or hypocalcemia due to PTH resistance), addressing developmental delays through early intervention programs, and orthopedic surveillance. Growth hormone therapy has been considered in some cases but evidence for its efficacy remains limited. Regular endocrine evaluations, developmental assessments, and audiological monitoring are recommended as part of ongoing care.

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