Pseudoachondroplasia is a hereditary disease from the group of osteochondrodysplasia, it is considered the most common condition of this type. Symptoms of this pathology are disproportionate dwarfism, curvature of the lower extremities (O- or X-shaped legs), increased mobility of the joints (except for the elbow) and other malformations of the skeleton. Diagnosis of pseudoachondroplasia is based on the data of the patient’s current status, X-ray studies, molecular genetic analyses. There is no specific treatment for this disease at the moment, various symptomatic measures (physiotherapy, surgical correction) are used to improve the quality of life of the patient.
Pseudoachondroplasia is a genetic disease characterized by a violation of the formation of cartilage tissue and enchondral bone and, as a consequence, osteoarthropathy. It is the most common variant of skeletal dysplasia, but at the same time it has manifestations of varying severity – from severe disproportionate dwarfism to stunting with minor changes in the skeleton.
Pseudoachondroplasia was first described in France by pediatrician Pierre Marot and geneticist Maurice Lamy in 1959, experts identified it as pseudoachondroplastic spondyloepiphyseal dysplasia. Only since 1969, this condition has been isolated into a separate nosological unit called pseudoachondroplasia. At the moment, it has been found out that this disease is characterized by an autosomal dominant inheritance mechanism and affects both boys and girls with the same frequency. The incidence of pseudoachondroplasia is estimated at 1:20,000, while its spread is widespread, racial or national characteristics of the distribution of the disease have not been revealed.
The cause of pseudoachondroplasia is defects in the COMP gene located on chromosome 19. Mutations of the same gene lead to another common variant of hereditary skeletal disorders – multiple epiphyseal dysplasia. COMP encodes a sequence of oligomeric cartilage matrix protein involved in the development of cartilage tissue, processes of enchondral ossification and tendon formation. A genetic defect in pseudoachondroplasia is a change in GAC repeats in the coding sequence of a gene, which entails a different content of aspartic acid in the protein from the norm. The normal COMP gene contains 5 GAC repeats, whereas in patients with pseudoachondroplasia, both a larger (6-7) and a smaller number of them are recorded.
The change in the amount of amino acid residues of aspartic acid in the oligomeric protein of the cartilaginous matrix manifests itself as an abnormal isoelectric point of this protein. As a result, the processes of intracellular transport of this protein are disrupted, it begins to accumulate in the rough endoplasmic reticulum of the cell. Extracellularly, its deficiency is formed, due to which the formation of cartilage and associated areas of bone tissue – metaphyses, epiphyses, vertebral bodies is disrupted, which manifests itself as pseudoachondroplasia. In addition, since the COMP gene is also expressed in the tissues of tendons and articular ligaments, patients with this disease have pathological changes in the joints and weakness of their ligamentous apparatus.
The above mutation (change in the number of GAC repeats) is inherited by an autosomal dominant mechanism with full penetrance, the question of spontaneous genetic defects leading to pseudoachondroplasia is currently debatable. The nature of deformities of the lower extremities and curvature of the vertebral column is strongly dependent on external factors – physical activity, the quality of patient care, his weight and activity. This causes a significant diversity of the clinical picture of pseudoachondroplasia in different patients.
As a rule, manifestations of pseudoachondroplasia are not detected in newborns. Pregnancy in the vast majority of cases proceeds normally, the physical parameters of the infant also do not detect anomalies. The first 2-3 years of life, the physical development of children without pathologies, then various signs of skeletal abnormalities begin to be detected. The first symptom of pseudoachondroplasia is often a change in the proportions of the body – there is a shortening of the limbs due to a decrease in the length of the shoulder and thigh bones, the palms and feet become wider, the fingers are short. At the age of 3-4 years, a pronounced lag in the growth and physical development of a sick child is already observed in comparison with healthy peers.
As the patient with pseudoachondroplasia grows, curvature of the spine occurs – mainly, an increase in lumbar lordosis. The gait changes, which becomes waddling. At an older age, curvatures of the lower extremities of various types (varus or valgus) can be detected – the severity of such deformity largely depends on the degree of load on the legs. Often, with pseudoachondroplasia, attention is drawn to the increased mobility of the joints, with the exception of the elbows – they are subjected to more or less pronounced flexion contracture. The growth of patients rarely exceeds 130 centimeters, in many cases there is a disproportionate dwarfism. With timely preventive treatment and orthopedic correction, the severity of this manifestation of pseudoachondroplasia can be significantly reduced.
Patients with pseudoachondroplasia may develop osteoarthritis, while the hip and knee joints are most severely affected. Pathological changes in the joints are manifested by soreness during movements and local edema, often crunching occurs in the joints. In the future, osteoarthritis can develop into a limitation of mobility and even cause severe disability of the patient. The time of development of osteoarthritis in pseudoachondroplasia and the rate of their progression largely depend on the degree of stress on the joints and the correctness of the prescribed treatment. Unlike many other hereditary dysplasias, the intellectual development of the patient does not suffer from this disease.
Determination of pseudoachondroplasia is made on the basis of data from the general examination of the patient, X-ray studies, molecular genetic analyses. A fairly accurate method of diagnosing this condition, which allows differentiating it from achondroplasia, is to determine the concentration of oligomeric protein of the cartilaginous matrix in blood plasma, but this technique is not available in every laboratory. When examining a patient with pseudoachondroplasia, the clinical picture of the disease depends on age. A 2-3-year-old child may have only a slight lag in growth and body disproportion. By the age of 4-5, these manifestations are accompanied by curvature of the spinal column and changes in gait. In older children and adults with pseudoachondroplasia, a significant shortening of the limbs, dwarfism is determined, signs of coxarthrosis and gonarthrosis are possible.
X-ray examinations in pseudoachondroplasia are also characterized by certain differences in patients of different ages. In childhood, the most frequent changes are a slowdown in the processes of ossification of the metaphyses of long tubular bones, platyspondylia (flattening of the vertebral bodies), shortening of the femoral and humerus bones. The femoral head is reduced, which leads to the expansion of the articular gap of the hip joint. At an older age (17-19 years old) in most patients with pseudoachondroplasia, the condition of the vertebral bodies improves somewhat, there is ossification of the metaphyses and epiphyses, but radiological signs of osteoarthritis of the knee and hip joints, as well as O- or X-shaped deformity of the legs may be detected.
A blood test for the level of the oligomeric protein of the cartilaginous matrix in pseudoachondroplasia shows its absence or extremely low level. In many cases, only this study and molecular genetic analysis help differentiate this disease from classical achondroplasia. With the help of the achievements of modern genetics, it is possible to perform direct automatic sequencing of the COMP gene in order to detect mutations. Given the autosomal dominant nature of pseudoachondroplasia, if one of the parents has this disease, the probability of inheritance is 50%.
There is no specific treatment for pseudoachondroplasia, but properly prescribed symptomatic and preventive therapeutic measures can significantly ease the course of the disease and improve the quality of life of patients. All the techniques used in the treatment of this condition belong to three varieties – conservative, physiotherapeutic (orthopedic techniques are often also included here) and surgical. As a rule, conservative and physiotherapeutic treatment aimed at preventing the development of severe skeletal deformities and osteoarthritis begins soon after the definition of pseudoachondroplasia in childhood. For the prevention of the latter, a long-term intake of chondroprotectors, drugs that improve blood circulation in the joints, physical therapy is prescribed. Physiotherapy methods – warming up, massages, magnetic therapy, electrophoresis and a number of others have a beneficial effect on the condition of joints with pseudoachondroplasia.
An important role in the prevention of deformities of the limbs and spine in pseudoachondroplasia is played by the use of orthopedic means – special shoes, knee pads to strengthen joints, a bandage for the back. In addition to using such means, it is important to limit static loads on the legs and back – prolonged standing, walking long distances are contraindicated. At an older age, in order to alleviate the condition of patients with pseudoachondroplasia, surgical correction of deformed bones (osteotomy) can be resorted to, operations to strengthen and even prosthetics of joints can be performed.
Prognosis and prevention
Most specialists assess pseudoachondroplasia as a condition with a favorable prognosis – despite dwarfism, disproportionality and deformities of bones, most patients retain mobility and relative ability to work. The greatest threat in this disease is a significant deformity of the legs, osteoarthritis of the hip and knee joints, but with proper treatment these problems can be avoided. In addition, it is possible to eliminate them surgically. The intelligence and fertility of patients with pseudoachondroplasia are completely preserved, but women should be especially careful when carrying a child because of the increased load on the spine and lower extremities. It is necessary to avoid work involving prolonged standing or walking. Prevention of pseudoachondroplasia is possible only within the framework of prenatal diagnosis in the case of the presence of such a disease in one of the parents.