Pycnodysostosis (PYCD)

(OMIM phenotype number #265800)

Pyknodysostosis is an autosomal recessive osteochondrodysplasia, first described in 1962 by Maroteaux and Lamy (Greek: pycnos = dense; dys = defective; osteon = bone). This disease is also called "Toulouse-Lautrec syndrome" after the famous French artist Henri de Toulouse-Lautrec, who was thought to be afflicted with the disorder. It is generally diagnosed during infancy or early childhood. Sometimes, the diagnosis is late and after a bone fracture, given the severe bone fragility resulting from increased bone density. More than 100 cases have been described since 1962. The prevalence of PYCD is estimated to be 1 to 1.7 per million with equal sex distribution. It is transmitted as an autosomal recessive trait and with a mutation in the Cathepsin K (CTSK) gene (nonsense, missense, and stop codon mutations have been described). Cathepsin K is a lysosomal cysteine proteinase that is highly expressed in osteoclasts, localized to the pycnodysostosis region, and is required for the degradation of collagen. Therefore, PYCD is due to an impaired degradation of the organic matrix of bone by osteoclast, caused by loss-of-function mutations of the CTSK gene.

The differential diagnosis is established with osteopetrosis, cleidocranial dysplasia and idiopathic acro-osteolysis.


CTSK gene, 1q21.3 (OMIM gene/locus number *601105)


Generalized high bone mass, bone fragility, disproportionate short stature, dwarfism, large cranium, dysmorphic features of the face, obtuse angle of mandible, clavicular dysplasia, fingers are short and clubbed from acro-osteolysis or aplasia of the terminal phalanges, hypoplastic fingernails, small and square hands, narrow thorax, pectus excavatum, kyphoscoliosis, increased lumbar lordosis, recurrent fractures typically involve the lower limbs and cause genu valgum deformity, long bones manifest hyperostosis and narrow medullary canals. The calvarium and base of the skull are sclerotic, and the orbital ridges are radiodense. Hypoplasia of facial bones and sinuses are characteristic of this disorder. Vertebrae are dense, yet their transverse processes are not involved. Lumbosacral spondylolisthesis is not uncommon.

Main biochemical alterations

Low GH, low IGF1.


Fig. The radiograph shows thin mandible, obtuse mandibular angle, malposed teeth, elongation of the condyle and coronoid process

Reproduced from Int J Clin Exp Med 201;7:492-6 under the terms of the Creative Commons Attribution License (CC BY).

Other resources


  1. Gelb BD, Shi GP, Chapman HA, et al. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996 Aug 30;273(5279):1236-8.
  2. Xue Y, Cai T, Shi S, et al. Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011. Orphanet J Rare Dis. 2011 May 10;6:20. doi: 10.1186/1750-1172-6-20.
  3. Alves Pereira D, Berini Aytés L, et al. Pycnodysostosis. A report of 3 clinical cases. Med Oral Patol Oral Cir Bucal. 2008 Oct 1;13(10):E633-5.
  4. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  5. Ihde LL, Forrester DM, Gottsegen CJ, et al. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82.
  6. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Nov;26(11):2717-8.