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Pycnodysostosis (from Greek: πυκνός (puknos) meaning "dense", dys ("defective"), and ostosis ("condition of the bone")), is a lysosomal storage disease of the bone caused by a mutation in the gene that codes the enzyme cathepsin K.
This is an autosomal recessive osteochondrodysplasia that maps to chromosome 1q21. Deficiency of Cathepsin K, a cysteine protease in osteoclasts, is known to cause this condition. Cathepsin K became a much sought-after drug target in osteoporosis after the etiology of pycnodysostosis was discovered. The disease consistently causes short stature. The height of adult males with the disease is less than 150 cm (59 inches, or 4 feet 11 inches). Adult females with the syndrome are even shorter.
The disease has been named Toulouse-Lautrec syndrome, after the French artist Henri de Toulouse-Lautrec, who may have suffered from the disease. In 1996, the defective gene responsible for pycnodysostosis was located, offering accurate diagnosis, carrier testing and a more thorough understanding of this disorder.
Pycnodysostosis causes the bones to be abnormally dense (osteopetrosis); the last bones of the fingers (the distal phalanges) to be unusually short; and delays the normal closure of the connections (sutures) of the skull bones in infancy, so that the "soft spot" (fontanelle) on top of the head remains widely open.
Those with the syndrome have brittle bones which easily break, especially in the legs and feet. The jaw and collar bone (clavicle) are also particularly prone to fractures.
Other abnormalities involve the head and face, teeth, collar bones, skin, and nails. The front and back of the head are prominent. Within the open sutures of the skull, there may be many small bones (called wormian bones). The midface is less full than usual. The nose is prominent. The jaw can be small. The palate is narrow and grooved. The baby teeth are late coming in and may be lost much later than usual. The permanent teeth can also be slow to appear. The permanent teeth are commonly irregular and teeth may be missing (hypodontia). The collar bones are often underdeveloped and malformed. The skin over the back of the fingers is very wrinkled. The nails are flat and grooved.
Pycnodysostosis also causes problems that may become evident with time. Aside from the broken bones, the distal phalanges and the collar bone can undergo slow progressive deterioration. Vertebral defects may permit the spine to curve laterally resulting in scoliosis. The tooth problems often require orthodontic care and dental caries are common.
The precise frequency of pycnodysostosis has not been determined. Pycnodysostosis can be classified in the large group of genetic diseases that are individually uncommon, but collectively important because of the sum of their numbers, and their heavy impact upon affected individuals.
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- Gelb, BD; Shi, GP; Chapman, HA; Desnick, RJ (1996). "Pycnodysostosis, a lysosomal storage disease caused by cathepsin K deficiency". Science 273 (5279): 1236–1238. doi:10.1126/science.273.5279.1236. PMID 8703060.
- Motyckova, G; Fisher, DE (2002). "Pycnodysostosis: role and regulation of cathepsin K deficiency in osteoclast function and human disease". Current Molecular Medicine 2 (5): 407–421. doi:10.2174/1566524023362401. PMID 12125807.