Chondrodysplasia is a common name for a group of hereditary diseases caused by a violation of the formation or ossification of cartilage tissue. They arise as a result of gene mutations, are inherited both by autosomal dominant and autosomal recessive type. Pathologies are manifested by stunting, various shortening and deformities of the limbs, joint damage. For diagnosis, radiography or computed tomography data, the results of a genetic study are required. Treatment is aimed at eliminating or correcting existing disorders, for which orthopedic operations, orthoses, physical therapy and physiotherapy methods are used.
Q77 Osteochondrodysplasia with defects in the growth of tubular bones and spine
Today, more than 100 variants of chondrodysplasia are known, many of which are similar in clinical picture, so making an accurate diagnosis is usually difficult. Diseases do not lose their relevance, since they are accompanied by gross deformations of the musculoskeletal system, which is fraught with disability, a sharp deterioration in the quality of life, some have a high mortality rate at an early age. There are no reliable statistical data on the prevalence.
Pathology is associated with point mutations of genes (COL2A1, SEDL, COMP, etc.) responsible for the formation of cartilage matrix proteins or some regulatory peptides. Most types of chondrodysplasia have an autosomal dominant type of inheritance — in the presence of a gene defect in one of the parents, the risk of having a sick child is 50%. Some forms are distinguished by an autosomal recessive transmission mechanism, for which both parents must be carriers of the mutant gene.
In most types of chondrodysplasia, a primary protein defect is detected: different types of collagen, matriline, and oligomeric protein. All of them normally make up cartilage tissue, therefore, with their pathological structure, structural defects, excessive or insufficient development of cartilage are observed. Violations also occur at the stage of formation of regulatory proteins, which include the tyrosine kinase receptor, transcription factors, and RNA processing enzymes.
Typical deformities and shortening of limbs are often combined with disorders of enchondral ossification, in which a non-structural disordered arrangement of chondrocytes is determined, caused by defects in oxidative phosphorylation. A number of forms of the disease are manifested by the formation of bone protrusions (exostoses). The pathogenetic mechanisms of many types of chondrodysplasia have not yet been precisely studied.
Modern genetics has adopted a comprehensive approach to the systematization of chondrodysplasias, taking into account etiopathogenetic, clinical and radiological features. The International Working Group on Chondrodysplasia presented a classification option of 17 sections according to the type of gene mutation. At the same time, in practical medicine, the division of the disease is relevant, taking into account the nature of the cartilage tissue lesion, which includes 3 categories:
- Epiphyseal dysplasia. This includes lesions of articular cartilage, dysplasia of cartilage tissue of the epiphysis proper. The main representatives of the group: Volkov disease, spondyloepiphyseal dysplasia, pseudoachondroplasia, Fairbank disease.
- Physical dysplasia. They are characterized by violations of the formation of the germinal epiphyseal plate. This category includes achondroplasia (chondrodystrophy), hypochondroplasia, exostatic chondrodysplasia.
- Metaphysical dysplasia. This group of pathologies occurs due to the delay of enchondral growth against the background of improper ossification of metaphyseal cartilage. They are the least studied, only a few variants have been described: dyschondroplasia (Ollier’s disease), chondrodysplasia of the type of Jansen, Schmid, Mccusick.
A typical sign of any form of the disease is low growth (dwarfism) associated with disorders of elongation of tubular skeletal bones. The height of adult patients is about 1.2-1.3 m. Dwarfism is accompanied by body disproportions: with relatively normal trunk sizes, such patients have short limbs, a large skull. With the early closure of the cranial sutures, the deformation of the head occurs.
Chondrodysplasia has many symptoms, depending on the specific variant of pathology. Achondroplasia sufferers have a large forehead, saddle-shaped nose, pronounced deflection in the lower back (lordosis), legs acquire a saber-shaped shape. Dystrophic dysplasia is characterized by elongation of the thumbs of the hands, equinovarus clubfoot. With epiphyseal dysplasia, shortening of the distal phalanges of the fingers, dislocations of the hip joints are noted.
In addition to symptoms from the musculoskeletal system, multiple somatic signs of chondrodysplasia are diagnosed. Changes in the skin and subcutaneous tissue are manifested by pigment spots, large lipomas, hemangiomas, large foci of hyperkeratosis often form on the palms and feet. Patients may experience hepatosplenomegaly, various eye lesions: lens dystrophy, astigmatism, myopia.
Some chondrodysplasias are attributed to lethal mutations, with their presence, only a few patients survive to adulthood. This category includes some types of achondrogenesis, thanatophoric dysplasia, capomelic dysplasia, rhizomelic form of point chondrodysplasia. Non-lethal consequences of the disease include joint contractures, deformities of the limbs, gross curvature of the spine by the type of kyphoscoliosis or lordosis.
Since the lesion of bone-cartilaginous structures usually affects the spine, patients have a risk of neurological disorders. They are caused by compression of the spinal cord with narrowing of the spinal canal or with stenosis of the large occipital foramen. Complications include sensitivity disorders, decreased skeletal muscle tone, pelvic disorders. Due to the deformation of the chest, respiratory failure often increases.
Gene mutations can affect not only cartilage tissue proteins, but also components of connective tissue fibers of other localization, which is associated with a complicated course of chondrodysplasia. Often, diseases are accompanied by malformations of the heart: the presence of additional chords, pathologies of the valvular apparatus, damage to large elastic vessels. When the muscular tissue of the heart is involved in the process, severe forms of cardiomyopathy occur.
The initial examination of patients is in the competence of an orthopedic traumatologist, if necessary, a geneticist, an orthopedic surgeon are involved in the examination. It is possible to suspect the presence of chondrodysplasia due to growth retardation in combination with multiple skeletal deformities, but it is difficult to identify a specific nosological unit based on physical data. The diagnostic plan includes the following research methods:
- Bone radiography. Radiological signs are diverse: flattening of the epiphyseal sections of the tubular bones, deformation of short tubular bones, uneven foci of ossification. A pathognomonic picture is observed with achondroplasia — in the picture, the cross-sections of the tubular bones are enlarged, the cortical substance is thickened, the metaphyses are expanded, the relief is enhanced.
- CT of skeletal bones. Computed tomography has a higher resolution, so the method is recommended for difficulties in the differential diagnosis of chondrodysplasia. CT is also informative in mild phenotypic variants, when there are no pronounced anomalies of the bone apparatus.
- Genetic testing. At the present stage of medicine, the genes responsible for most variants of chondrodysplasia have been deciphered. To verify the diagnosis, exon sequencing is used, which is performed on the basis of specialized genetic centers. According to the indications, testing is carried out to the patient’s closest relatives.
Specific therapy has not been developed. The essence of medical care is to restore the normal proportions of the skeleton as much as possible, improve the functionality of the limbs, and prevent severe disability. An important role is played by explaining to patients the inadmissibility of increased loads on the joints, which can cause a sharp deterioration of the condition. The complex of therapeutic measures for chondrodysplasia consists of the following areas:
- Orthopedic correction. The use of special orthoses, fixators (for example, in case of dislocation of the hip joint) partially compensates for the existing anatomical anomalies. To improve the gait, special orthopedic shoes are selected.
- Surgical interventions. A good functional and cosmetic result is provided by limb lengthening operations, which are performed in several stages. Also, surgical assistance is indicated for the elimination of large exostoses, the elimination of articular contractures, and the correction of spinal canal stenosis.
- Rehabilitation. Patients with chondrodysplasia are assigned individual courses of physical therapy, mechanotherapy, special massage. Physiotherapy procedures are useful to reduce muscle tension.
Prognosis and prevention
Among chondrodysplasias, there are lethal variants that lead to fetal death in the prenatal period or early death of a child, and mild forms in which successful rehabilitation and socialization of patients is possible. Timely assistance of orthopedic surgeons and comprehensive rehabilitation is of great importance for improving the prognosis. Taking into account the genetic background of the disease, effective preventive measures have not been developed.