Pycnodysostosis
Encyclopedia
Pycnodysostosis from 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
.
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 (it has been surmised) 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.
); 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" (fontanel) 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 last bones of the fingers (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 cavities are common.
Lysosomal storage disease
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function...
of the bone caused by a mutation in the gene that codes the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
cathepsin K
Cathepsin K
Cathepsin K, abbreviated CTSK, is an enzyme which in humans is encoded by the CTSK gene.- Function :The protein encoded by this gene is a lysosomal cysteine protease involved in bone remodeling and resorption...
.
Genetics
This is an autosomal recessive osteochondrodysplasia maps to chromosome 1q21. Cathepsin K, a cysteine protease in osteoclasts, deficiency is known to cause this condition. Interestingly, Cathepsin K became a much sought after drug target in osteoporosisOsteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
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
Henri de Toulouse-Lautrec
Henri Marie Raymond de Toulouse-Lautrec-Monfa or simply Henri de Toulouse-Lautrec was a French painter, printmaker, draughtsman, and illustrator, whose immersion in the colourful and theatrical life of fin de siècle Paris yielded an œuvre of exciting, elegant and provocative images of the modern...
, who (it has been surmised) 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.
Symptoms
Pycnodysostosis causes the bones to be abnormally dense (osteopetrosisOsteopetrosis
Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schonberg disease is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle,...
); 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" (fontanel) 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 last bones of the fingers (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 cavities are common.