Pyknodysostosis is a rare lysosomal storage disease that follows an autosomal recessive inheritance pattern. It typically involves multiple skeletal deformities, as well as dwarfism. Features can be observed both clinically and radiologically.
Pyknodysostosis is a genetic disease that is inherited with an autosomal recessive pattern. It is caused by a mutation in chromosome 1q21, which, in turn, leads to the production of a defective cystine protease, an enzyme found in lysosomes, called cathepsin K (CTSK), which normally breaks down type 1 collagen fibers. The end result of this process is dense, brittle bones . Pyknodysostosis is rare, and some cases have been linked with consanguinity . Males are predominantly affected, while the onset of the disease is often observed in children and young adults .
Clinically, the condition presents with dental abnormalities such as crowding due to persisting deciduous teeth, a tendency to form dental caries, dental abscesses, enamel erosion, hypercementosis and short dental roots  . Further deformities in the oral cavity include macroglosia and a ridged or high-arched palate .
Musculoskeletal signs include dwarfism, limb and digit anomalies, frequent fractures, poorly formed clavicles and craniosynostosis (premature closure of sutures in infants, resulting in abnormal skull shape). Moreover, other features that include respiratory problems, and Arnold-Chiari malformation, have been described . There are variant genotypes of the condition that present with more severe, earlier-onset symptoms . Of note, individuals who suffer from pyknodysostosis are not typically anemic, and this can help distinguish the disease from similar bone disorders such as osteopetrosis.
The diagnosis, as well as the evaluation of the extent of pyknodysostosis, relies mainly on the clinical picture, as well as on imaging modalities. The commonly used techniques are:
Histological analysis of bone is carried out, and may demonstrate features such as attenuated central canals in the Haversian system and abnormal medullary canals . Molecular testing to detect the mutation in the gene coding for CTSK confirms the diagnosis .