pycnodysostosis

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by dense, brittle bones, short stature, and distinctive craniofacial and dental abnormalities. It results from loss-of-function mutations in the CTSK gene, which encodes cathepsin K, a protease essential for osteoclast-mediated bone resorption and normal bone remodeling.

Pathophysiology involves defective bone resorption, leading to generalized osteosclerosis with impaired remodeling. Although bones appear overly dense on radiographs, they are prone to fractures. A hallmark feature is acro-osteolysis of distal phalanges, along with persistent open cranial fontanelles and sutures, midface hypoplasia, and a beaked nasal bridge. Dental anomalies, including delayed eruption, hypodontia, and malocclusion, are common. Growth is usually limited, resulting in short stature, while cognitive development is typically preserved.

Diagnosis is suggested by the combination of clinical features and characteristic radiographs and is confirmed by molecular testing for CTSK mutations. Imaging often shows diffuse skeletal sclerosis with specific findings such as acro-osteolysis and open sutures, while dental radiographs reveal delayed tooth eruption and other anomalies.

Management is supportive and multidisciplinary. There is no cure. Care focuses on fracture prevention and safe handling, orthodontic and dental management for malocclusion and eruption issues, monitoring for airway problems and craniofacial complications, and addressing any cranial nerve or respiratory symptoms. Genetic counseling is important due to autosomal recessive inheritance. Prognosis varies but with appropriate care, individuals can have preserved intelligence and a normal lifespan, though fractures and dental problems may affect quality of life.