Pycnodysostosis is a disease of the osteopetrosis group of forms. It is characterized by the constant buildup of bone material without the breakdown of old bone components. However, the disease remains confined to the bones, unlike the other syndromes of this form circle.
What is pycnodysostosis?
Pycnodysostosis was first described in 1962. It is a very rare hereditary bone disease characterized by the constant increase of bone mass. There are no data on the exact prevalence of this disease. However, the incidence is still believed to be less than one in a million. Overall, only a few hundred cases of this disease have been observed to date. The leading symptom is increased bone fragility, because the inability of osteoclasts to function means that no remodeling processes can take place in the bone. The bones are therefore constantly built up without the old bone substance being broken down. As a result, a very high bone density develops. However, this is associated with extreme brittleness of the bones. Pycnodysostosis thus belongs to the group of osteopetroses. In contrast to the classical osteopetroses, which have been described time and again in the past centuries, pycnodysostosis does not usually show any anemia or cranial nerve damage. Therefore, it can be easily distinguished from other osteopetroses. In the past, the diseases of the osteopetrosis group were also called marble bone disease. This name indicates that the bones are very dense and strong, but also extremely brittle and fragile. The reason for this condition is the lack of degradation processes by osteoclasts. Thus, new substance is constantly added to the old bone substance without the remodeling process, resulting in a loss of elasticity of the bones.
Causes
The cause of pycnodysostosis is due to a gene mutation of a gene on chromosome 1. This is the gene CTSK, which is responsible for coding for the enzyme cathepsin K. Cathepsin K stimulates bone resorbing cells (osteoclasts) to break down bone substance as part of the remodeling process. For lack of cathepsin K, this process cannot take place here. Only new bone substance is constantly built up. The disease is autosomal recessive heritable.
Symptoms, complaints, and signs
Pycnodysostosis manifests primarily as osteosclerosis. In contrast to osteoporosis, osteosclerosis is characterized by constant bone formation, which results in high bone density. However, the bones are fragile and prone to spontaneous fractures. At the same time, patients exhibit moderate short stature. The height can reach up to 1.50 meters. Acroosteolysis occurs unexplained at the terminal phalanges. This means that the end phalanges of the finger and toe bones show signs of dissolution. Furthermore, the clavicle appears dysplastic. In addition, characteristic skull anomalies occur, which are manifested by an enlarged skull volume, switching bones between the individual skull plates and the persistence of the large fontanel. In addition, there may be defective and abnormally shaped teeth (pointed and conical), which are also poorly positioned. Tooth eruption is often delayed. Brittle and irregularly shaped nails sometimes occur. Anemia and cranial nerve damage are not usually part of the symptom complex of pycnodysostosis. However, in very rare cases, anemia, enlarged liver, sleep apnea, respiratory problems, and general hematologic disorders may occur. Mental development is normal.
Diagnosis and course of the disease
Pycnodysostosis is a rare disorder but also easily distinguishable from other osteopetroses. The genetic defect is defined as a mutation in gene CTSK on chromosome 1. A family history may clarify whether cases of this disease have occurred in the immediate family. Differentially, pycnodysostosis must be differentiated from other osteopetroses, osteoporosis, kleidocranial dysplasia, and idiopathic acroosteolysis. Pycnodysostosis can be confirmed by radiographic studies of the skull and skeleton. Genetic testing should provide complete certainty.
Complications
Because of pycnodysostosis, affected individuals suffer from relatively high bone density.However, despite the increased bone density, the bones are fragile and break easily, so patients suffer from fractures and other injuries more often due to pycnodysostosis. Therefore, patients usually rely on increased precautions to prevent serious injuries from occurring. However, it is not uncommon for small stature to occur as well. In some cases, pycnodysostosis can also negatively affect the teeth, causing them to break easily or have an unnatural shape. Most affected individuals also suffer from brittle nails due to the disease, which also have an irregular shape. Some internal organs may be enlarged due to the disease and it is not uncommon to experience breathing difficulties. However, pycnodysostosis does not negatively affect the patient’s mental development. Causal treatment of pycnodysostosis is usually not possible. The affected person is dependent on regular checks and examinations to prevent pinching of nerves. In the worst case, this can lead to paralysis over the entire body. The patient’s life expectancy is usually not affected by pycnodysostosis.
When should you see a doctor?
Pycnodysostosis must always be treated by a physician. It is not possible to treat the condition with self-help remedies. The doctor should be consulted for pycnodysostosis if the affected person suffers from various bone complaints. This may include short stature or deformities. Here, especially the parents must observe the child and inform the doctor if necessary. Furthermore, deformations of the teeth or nails may indicate pycnodysostosis and must also be examined by a doctor. This is the only way to avoid further complications. Pycnodysostosis is diagnosed and treated by a pediatrician or a general practitioner. Special complications do not occur. However, since the disease can also affect the internal organs, they should be examined regularly.
Treatment and therapy
Because of the hereditary nature of the disease, causal therapy is not possible. Treatment can only be symptomatic. This requires interdisciplinary cooperation between physicians. Constant orthopedic monitoring of the patient is important. Bone fractures that are very difficult to heal have to be treated again and again. However, the treatment concept also includes constant monitoring of the statics of the spine. The spine tends to develop spondylolisthesis. Spondylolisthesis is an instability of the spine characterized by the fact that its upper section can slide forward with the slipped vertebra. However, this cannot be easily detected, since this change is not immediately visible and, moreover, does not necessarily cause discomfort. However, there is a risk of nerve entrapment, which can eventually cause severe pain and paralysis. The prognosis of pycnodysostosis is favorable. It is not curable, but there is also no progressive deterioration in the course of the disease.
Prevention
Pycnodysostosis is a hereditary disease with an autosomal recessive mode of inheritance. In affected families, genetic counseling can help prevent passing this condition on to offspring. First, genetic testing should be performed. If both parents carry this gene, there is a 25 percent chance for the offspring to inherit this disease. For people who already have the disease, prophylaxis against further bone fractures and spinal changes consists mainly in constant medical monitoring.
Aftercare
Since treatment of pycnodysostosis can only be symptomatic and the disease is incurable, there is no aftercare for the disease in the strict sense. Nevertheless, regular visits to the doctor and follow-up of some treatments are inevitable. The fractures caused by pycnodysostosis require regular medical monitoring. Since the disease makes healing of fractures more difficult and complications more likely, this should be more intensive than for ordinary fractures. Regular monitoring for spondylolisthesis is important because it is more common in patients with pycnodysostosis. If the patient has already had such a spondylolisthesis, this must also be followed up.Orthopedic rehabilitation measures accompanied by a physician or orthopedist are offered after successful treatment of spondylolisthesis and freedom from pain of the patient. Usually, they can be used after about twelve weeks. These measures usually consist of physiotherapy exercises, relaxation exercises and sports activity, which can also be combined with other measures such as psychotherapy. These measures are intended to strengthen the abdominal and back muscles. Likewise, general orthopedic control of the patient is necessary, since pycnodysostosis is not a progressive disease and can generally be treated well, but concomitant symptoms can always occur.
