Pyknodysostosis

Peter L. Munk and Anthony G. Ryan

Our patient was an infant boy in the lowest percentile for height and developmental delay.

Figure 40A

Figure 40B

Pyknodysostosis.

• Osteopetrosis
  
• Down syndrome

Pyknodysostosis is a rare (fewer than 130 cases described) congenital disorder with autosomal recessive transmission, the clinical, and some radiographic, manifestations of which were first described by Maroteaux and Lamy in 1962. Patients with this syndrome have patchy to diffuse osteosclerosis.

Pyknodysostosis is an autosomal recessive congenital abnormality resulting in mutations in the CTSK gene at 1q21, which codes for cathepsin K.

Cathepsin K is a lysosomal cysteine protease that plays a key regulatory role in bone metabolism, abnormalities of which interfere with bone resorption and remodeling. Bone resorption is further compromised by diminished osteoclast activation secondary to a global reduction in interleukin-1 secretion.

Males are affected twice as often as females. Patients are generally of short stature, with slightly misshapen skulls that have frontal and occipital bossing. Often the maxilla is small, as is the mandible, giving rise to a typical facial appearance of a receding jaw and a beaked nose. The teeth are frequently stained yellow and malformed (dysodontiasis).

• Reduced mental capacity is present in a minority of cases (10%).
  
• Broad hands and feet are peripheral features.
  
• Patients are prone to experience an appreciably increased number of fractures.
  
• Visceral manifestations such as hepatosplenomegaly are reported but are uncommon.
  
• Rare manifestations of this condition include extramedullary hematopoiesis and obstructive airways disease.