- Pycnodysostosis (Pyknodysostosis) Center
- Fat-Fighting Foods Slideshow
- Take the Human Body Quiz
- Causes of Fatigue Slideshow Pictures
- Pycnodysostosis facts
- What is pycnodysostosis?
- What is basis for the name of this disease?
- What are the characteristics of pycnodysostosis?
- How is pycnodysostosis inherited?
- What are the risks of pycnodysostosis?
- What is the molecular story with pycnodysostosis?
- Could there be a connection between pycnodysostosis and osteoporosis?
- What is the treatment for pycnodysostosis?
- Pycnodysostosis is an inherited disorder of the bone.
- Pycnodysostosis causes short stature.
- Pycnodysostosis causes abnormally dense brittle bones.
- Pycnodysostosis causes the "soft spot" of a baby's skull to stay widely open.
- Pycnodysostosis is due to a defect in an enzyme: cathepsin K.
- Growth hormone treatment may increase growth in pycnodysostosis.
What is pycnodysostosis?
Pycnodysostosis is perhaps best known as the diagnosis given retrospectively to the late 19th century French artist Henri de Toulouse-Lautrec (portrayed by Jose Ferrer in the 1952 film "Moulin Rouge").
Pycnodysostosis is a genetic (inherited) disease of the bone. Its pattern of inheritance follows the classic rules of genetics (see below).
Pycnodysostosis 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 pycnodysostosis are even shorter.
Pycnodysostosis causes the bones to be abnormally dense (osteosclerosis); 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" (the fontanel) on top of the head remains widely open.
Pycnodysostosis causes brittle bones which easily break (fracture). The bones in the legs and feet tend to fracture. The jaw and collar bone (clavicles) are also particularly prone to fractures.
The precise frequency of pycnodysostosis has never 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, their heavy impact upon affected individuals, and the equally heavy burden they place upon their families.
What is basis for the name of this disease?
The name for this disease was coined by the French physicians Maroteaux and Lamy in 1962. They described the disorder in a report entitled "La pycnodysostose." (They were not the only discoverers of the disease. Andren and colleagues independently described the condition in 1962.) Maroteaux and Lamy put "pyknos," from the Greek meaning "dense" together with the compound word "dysostosis" meaning abnormal bone formation. The name "pycnodysostosis" was designed to convey the abnormally dense bone that is a hallmark of the disease.
Although the original Maroteaux and Lamy spelling was with a 'c', it has been written variably with a 'c' or a 'k'. Here we use the original spelling with a 'c'. No matter which way it is spelt, the name has stuck and is utilized worldwide today to designate this disease.
What are the characteristics of pycnodysostosis?
Pycnodysostosis causes abnormalities other than short stature, dense brittle bones, short fingers, and the wide open soft spot of the skull (see above). These 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.
How is pycnodysostosis inherited?
Pycnodysostosis is an autosomal recessive condition. It is autosomal in that the gene for pycnodysostosis is situated on one of the non- sex chromosomes (autosomes). Pycnodysostosis is recessive in that a single edition of the pycnodysostosis gene is not enough to cause the disease. Two copies of the abnormal gene (one from each parent) must be present for the disease to develop. The presence of a normal gene from one or both parents prevents the disease.
What are the risks of pycnodysostosis?
Pycnodysostosis is a rare disease so that, if there is no family history of the disease, the risk for a child to have pycnodysostosis is very low.
However, with a inbred (consanguineous) union, the risk of pycnodysostosis rises a little. This means that if one parent carries a rare gene like that for pycnodysostosis, the chance that a mate of theirs who is actually related also carries the same rare gene is increased compared to an unrelated mate.
In a family with a child with pycnodysostosis, the risks are much higher. The parents of a child with pycnodysostosis have no signs of the disease themselves but they each carry a single edition of the pycnodysostosis gene and, with a given pregnancy, each has a half chance of transmitting the pycnodysostosis gene (versus the normal paired gene). It is like tossing a coin. The chance for the child to have pycnodysostosis is one-half (from one parent) times one-half (from the other parent). The overall risk of pycnodysostosis in the offspring of parents carrying the gene is, therefore, one-quarter (25%). Just as coins have no memory of a prior toss, the 25% odds of having a pycnodysostosis child apply to every pregnancy conceived together by these parents, irrespective of the status of any of their other children.
What is the molecular story with pycnodysostosis?
In 1995, the gene for pycnodysostosis was first charted by Gelb and associates. It was found to travel preferentially with gene markers known to be in chromosome region 1q21. (This tendency for genes to travel together is termed linkage). Once the location of the pycnodysostosis gene was identified by linkage analysis, genes in that region that seemed logical candidates were seriously scrutinized. Among them was cathepsin K, which is active in bone. Cathepsin K qualified as a "candidate gene."
In 1996, patients with pycnodysostosis were shown by Gelb and coworkers consistently to have mutational changes in the gene for cathepsin K. The defective cathepsin K gene was thus demonstrated to be the gene responsible for pycnodysostosis. Pycnodysostosis is now clearly recognized as being due to cathepsin K deficiency.
What does cathepsin K normally do? Cathepsin K is an enzyme (a catalyst for a reaction of body metabolism) of the type called a cysteine protease. This protease is important in cells of normal bone (osteoclasts) that are responsible for bone reabsorption (or resorption). It is thought that osteoclasts in patients with pycnodysostosis are hampered by a lack of cathepsin K and cannot adequately reabsorb that component of bone called the organic matrix. (This process is essential for normal bone maintenance; a process referred to as remodeling). Because of this inadequate resorption, the bones in pycnodysostosis are abnormally dense and brittle.
Could there be a connection between pycnodysostosis and osteoporosis?
Both pycnodysostosis and osteoporosis cause brittle bones. However, pycnodysostosis is a disease with abnormally dense bones, whereas osteoporosis is exactly the opposite, a disease with washed-out porous bones. There would seem to be no conceivable connection between pycnodysostosis and osteoporosis.
The new findings about cathepsin K and pycnodysostosis have made it clear that cathepsin K is a major protease in bone resorption. Given this function, it may well have a role in osteoporosis. Cathepsin K may, in fact, provide a rational basis for a new approach to the treatment of osteoporosis. This is an excellent illustration of how research on a rare disease may bring benefits to those affected by a common disease.
What is the treatment for pycnodysostosis?
Bone fractures are a big problem for patients with pycnodysostosis. They can occur with minimal stress. It is important that the disease be diagnosed and the tendency to fractures be recognized so that (1) fractures can be minimized, if not entirely prevented; and (2) the parents and other caregivers are not falsely accused of child abuse! As with any condition causing brittle bones, the infant should be handled with a reasonable degree of care. The older child should be encouraged to engage in safer forms of exercise such as swimming rather than, for example, jumping on a trampoline.
In 1996, Soliman and colleagues reported that there is defective secretion of growth hormone in pycnodysostosis. Replacement treatment with growth hormone was then tested. It was found to increase the growth of the length of bones (linear growth). Since short stature is an important consequence of pycnodysostosis, growth hormone treatment may prove very useful.
Health Solutions From Our Sponsors
"Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency."
Gelb BD, Shi GP, Chapman HA, Desnick RJ
Top Pycnodysostosis Related Articles
Broken Bone (Types of Bone Fractures)
A broken bone is a fracture. There are different types of fractures, such as:
- vertebral compression,
- compound, and
Symptoms of a broken bone include pain at the site of injury, swelling, and bruising around the area of injury. Treatment of a fracture depends on the type and location of the injury.
CavitiesLearn more about cavities including symptoms, treatment, and prevention. See how tooth decay, plaque, and bacteria contribute to the creation of cavities and how regular brushing and flossing can help prevent dental caries.
Exercise and ActivityRegular physical activity can reduce the risk of disease. Regular exercise can also reduce the symptoms of stress and anxiety. There are fitness programs that fit any age or lifestyle.
Genetic CounselingYour health care provider may refer you to a genetic professional. Universities and medical centers also often have affiliated genetic professionals, or can provide referrals to a genetic professional or genetics clinic. Genetic counseling provides patients and family members the tools to make the right choice in regard to test for a disease or condition.
Genetic DiseaseThe definition of a genetic disease is a disorder or condition caused by abnormalities in a person's genome. Some types of genetic inheritance include single inheritance, including cystic fibrosis, sickle cell anemia, Marfan syndrome, and hemochromatosis. Other types of genetic diseases include multifactorial inheritance. Still other types of genetic diseases include chromosome abnormalities (for example, Turner syndrome, and Klinefelter syndrome), and mitochondrial inheritance (for example, epilepsy and dementia).
Pregnancy Planning (Preparing for Pregnancy)
Pregnancy planning is an important step in preparation for starting or expanding a family. Planning for a pregnancy includes taking prenatal vitamins, eating healthy for you and your baby, disease prevention (for both parents and baby) to prevent birth defects and infections, avoiding certain medications that may be harmful to your baby, how much weight gain is healthy exercise safety and pregnancy, travel during pregnancy.
ScoliosisScoliosis causes an abnormal curvature of the spine. When the cause of scoliosis is unknown the disorder is described based on the age when the scoliosis develops (infantile, juvenile, or adolescent idiopathic scoliosis). In functional scoliosis, curvature develops due to a problem somewhere else in the body. With neuromuscular scoliosis, there is a problem when the bones of the spine are formed. Treatment typically involves observation, bracing, and surgery and is dependent upon the severity of the curvature.
StressStress occurs when forces from the outside world impinge on the individual. Stress is a normal part of life. However, over-stress, can be harmful. There is now speculation, as well as some evidence, that points to the abnormal stress responses as being involved in causing various diseases or conditions.
Stress Management TechniquesStress may be considered as any physical, chemical, or emotional factor that causes bodily or mental unrest and that may be a factor in disease causation. An important goal for those under stress is the management of stress in our lives. Elimination of stress is unrealistic, since stress is a part of normal life. We can however, learn to manage stress through techniques such as exercise, relaxation, meditation, time management, and support systems so that we have control over our stress and its effects on our physical and mental health.