Skip to Main Content
  • Become an Access Reviewer
  • Clinical Phenotypes
  • OMMBID Advisory banner
  • Ommbid banner
  • Ommbid latest banner



  1. Pycnodysostosis, an inborn error of bone matrix degradation, results from the deficient activity of the lysosomal protease, cathepsin K, in the osteoclasts of affected individuals. The enzymatic defect leads to a reduced ability of osteoclasts to remove organic bone matrix, which causes defective bone growth and remodeling. Partially degraded collagen fibrils are found in lysosomes within osteoclasts that are actively resorbing bone.

  2. The disorder is transmitted as an autosomal recessive trait by the gene encoding cathepsin K, localized to chromosomal region 1q21. The human cathepsin K cDNA and genomic sequences have been isolated, characterized, and used to analyze the mutations causing pycnodysostosis. All identified defects have been point mutations in the coding region, which obliterate the collagenolytic activity of the mature enzyme.

  3. Clinical manifestations include short stature, a typical dysmorphic appearance, generalized osteosclerosis, dysplastic bones including hypoplasia of the distal phalanges, clavicles, and various craniofacial bones, as well as pathologic fractures and dental abnormalities. Associated complications include osteomyelitis of the jaw, upper airway obstruction, growth hormone deficiency, and myelophthisis. Life span is normal, although disability secondary to the orthopedic problems may cause premature demise.

  4. Diagnosis is usually made by clinical and radiologic examinations. Demonstration of cathepsin K gene defects confirms the diagnosis. Prenatal diagnosis can be accomplished by demonstration of the specific cathepsin K mutation(s) in chorionic villi or cultured amniotic cells, or by linkage analysis for couples known to be cathepsin K mutation carriers.

  5. Therapy is directed at preventing or ameliorating the orthopedic, dental, and medical complications. Surgical intervention may be necessary for patients with significant upper airway obstruction. Growth hormone repletion may improve linear growth for individuals with growth hormone deficiency.

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

OMMBID Full Site: One-Year Subscription

Connect to the full suite of OMMBID content including new and revised chapters that reflect the latest research, image galleries, clinical phenotypes, and more.

$295 USD
Buy Now

Pay Per View: Timed Access to all of OMMBID

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.