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Pycnodysostosis
Disease definition
Pycnodysostosis is a genetic lysosomal disease characterized by osteosclerosis of the skeleton, short stature and brittle bones.
ORPHA:763
Classification level: DisorderSummary
Epidemiology
It is very rare, the exact prevalence is unknown but it is less than 1/100,000.
Clinical description
The disease is discovered at variable ages, ranging from 9 months to 50 years. The condition is most often diagnosed in childhood, but sometimes the condition is not detected until adulthood, usually as a result of a fracture or a routine examination. The most frequent clinical or radiological manifestations of the disease are osteosclerosis, short stature or dwarfism, acroosteolysis of the distal phalanges, fragile bones associated with spontaneous fractures and dysplasia of the clavicles. Patients present with characteristic cranial malformations: a voluminous skull with wormian bones present and persistence of the anterior fontanelle, and a small mandible. Dental abnormalities such as decayed, poorly located or abnormally shaped (pointed or conical) teeth and delayed tooth eruption may be observed. Nails are sometimes irregular and cracked. Very rarely, the disease is associated with anemia, hepatosplenomegaly, hematologic alterations, respiratory distress and sleep apnea. The short stature is variable but moderate (1.35m to 1.50m).
Etiology
Pycnodysostosis is due to mutations in the gene encoding cathepsin K (localized to 1q21), a lysosomal enzyme secreted by osteoclasts, which allows the division of proteins of the bone matrix (collagen type I, osteonectin or osteopontin).
Diagnostic methods
Diagnosis is clinical and should be confirmed by radiographic examination of the entire skeleton and skull.
Differential diagnosis
Differential diagnoses include osteoporosis, osteopetrosis, cleidocranial dysplasia and idiopathic acroosteolysis (see these terms).
Genetic counseling
Inheritance is autosomal recessive.
Management and treatment
Management is symptomatic and multidisciplinary. It includes orthopedic monitoring, treatment of fractures, of which consolidation is sometimes slow, and static vertebral surveillance to detect frequent spondylolisthesis.
Prognosis
The prognosis is favorable; the disease is not progressive.
A summary on this disease is available in Deutsch (2008) Español (2008) Français (2008) Italiano (2008) Nederlands (2008)
Detailed information
General public
- Article for general public
- Svenska (2019) - Socialstyrelsen
Disease review articles
- Review article
- English (2009) - Orphanet J Rare Dis


Additional information