Diastrophic dysplasia is one of the varieties of skeletal dysplasia, which is characterized by a violation of the formation of certain types of cartilage tissue and the associated hindered formation of endochondral bone. The symptoms of the disease are detected immediately at birth or as part of prenatal diagnosis and consist in a reduced length of the newborn’s body and stunting in the future, joint contracture, scoliosis and other malformations. Diagnosis of diastrophic dysplasia is made on the basis of the patient’s examination data, X-ray and molecular genetic studies. There is no specific treatment of pathology, symptomatic therapy is used. If characteristic disorders are detected in the early stages of carrying a child, pregnancy is terminated for medical reasons.
Diastrophic dysplasia is a hereditary disease from the group of bone-cartilaginous dysplasia, characterized by numerous malformations of the skeleton. For the first time this pathology was described in 1960 by the French geneticist M. Lamy together with his student, pediatrician P. Maroto. The researchers were able to determine the features of skeletal abnormalities in this condition and establish their hereditary nature. Diastrophic dysplasia is a disease with an autosomal recessive inheritance mechanism. It is very rare, which makes it somewhat difficult to reliably determine its prevalence. At the same time, it was found out that this condition is more common in the Baltic countries, especially in Finland. Due to the autosomal recessive transmission of diastrophic dysplasia, the sexual distribution of the disease does not have any features – both boys and girls suffer equally from it.
The main cause of the development of diastrophic dysplasia is a mutation in the SLC26A2 gene, which is located on the 5th chromosome. This gene is widely known in medical circles, as its defects cause a large number of hereditary and congenital anomalies of skeletal development, including some types of achondrogenesis and atelosteogenesis, multiple epiphyseal dysplasia and De la Chapelle syndrome. The reason is that SLC26A2 encodes a special protein-a carrier of sulfate ions, which is actively involved in the formation of proteoglycans of cartilage and other connective tissues. Gene mutations of different types lead to unequal structural changes in this protein, which, in turn, changes its functional activity in different ways and causes a variety of malformations.
According to modern genetics, the cause of the development of diastrophic dysplasia (especially the Finnish type) is a mutation IVS1+2T>C. At the same time, the sulfonation of cartilage proteoglycans becomes insufficient, which leads to the accumulation of “unprocessed” products in the matrix of cartilage tissue. Cartilage density and its functional activity are disrupted, which leads to problems in the formation of bones with endochondral ossification (bones of the trunk, limbs and the base of the skull). It is these processes that cause almost all the symptoms of diastrophic dysplasia that are observed in patients and are detected during prenatal diagnosis. All mutations of the SLC26A2 gene are divided into lethal and non-lethal. Diastrophic dysplasia belongs to the latter group, patients in some cases are able to live to an advanced age.
The first symptoms of diastrophic dysplasia can be detected immediately at the birth of a child. Neonatologists register a reduced body length (no more than 42 centimeters) and body weight (up to 2800 grams) at normal gestation periods. This indicates an intrauterine delay in fetal development, which can often be detected during preventive ultrasound examinations. Other early postnatal manifestations of diastrophic dysplasia include microcephaly and inflammation of the cartilage of the auricles, which develops during 1-5 months of a child’s life. After the inflammation subsides, the cartilaginous base of the organ is deformed.
In the future, a patient with diastrophic dysplasia develops a number of other pathologies: deformities of the hand with stiffness in the interphalangeal joints, short fingers, pronounced proximal location of the thumb. Contractures of the hip and knee joints occur. The long tubular bones of the limbs are shortened relative to the proportions of the body. A decrease in the length of the limb bones leads to stunting of patients with diastrophic dysplasia, the average height of men with this pathology is 132 centimeters, women – 126 centimeters. Progressive curvature of the spine (scoliosis, kyphosis) is revealed. Other disorders (in particular, disorders of the intellect and endocrine system) in diastrophic dysplasia, as a rule, are not observed.
Diagnosis of diastrophic dysplasia is based on the data of physical examination, X-ray examination of the skeleton and molecular genetic analysis. When examining a newborn, signs of prenatal lag in physical development are noted (reduced body length and weight, microcephaly), in the future these indicators remain lower than in healthy peers. At an older age, diastrophic dysplasia reveals short limbs, deformities of the hands and fingers, contractures of the knee and hip joints, low growth. Almost 80% of patients have thickening and deformation of the cartilage of the auricles as a consequence of inflammation suffered in early childhood.
Radiologically, in patients with diastrophic dysplasia, a decrease in the relative length of the tubular bones of the extremities is determined, often combined with their arcuate deformation. The expansion of metaphyses, deformation of the femoral heads, subluxations and dislocations of large joints (knee, elbow, hip) are revealed. The metacarpal bones and phalanges of the fingers are often shortened, similar changes are visible on the metatarsal bones. Almost always, with diastrophic dysplasia, curvature of the spine is detected – scoliosis and kyphosis of varying severity. Molecular genetic diagnosis of the disease is reduced to direct sequencing of the SLC26A2 gene in order to confirm characteristic genetic defects. This method allows the most accurate differentiation of diastrophic dysplasia from other skeletal abnormalities caused by mutations of SLC26A2.
Treatment and prognosis
There is no specific treatment for diastrophic dysplasia, symptomatic correction of disorders is carried out, including surgical methods. Possible operations include interventions to eliminate curvature and fixation of the spinal column, shown in severe damage to the spinal roots. With moderate sciatica, anti-inflammatory drugs, physiotherapy, therapeutic gymnastics and other techniques are used. The prognosis of diastrophic dysplasia regarding the survival of patients is uncertain, even with a favorable outcome, the condition becomes a cause of disability. In some cases, patients with this pathology live to adulthood and even old age.
Preventive measures for diastrophic dysplasia are reduced to timely prenatal diagnosis of the disease and determination of the carrier of the pathological form of the SLC26A2 gene. By means of ultrasound examination, pathology can be detected in the fetus from the second trimester of gestation. When dysplasia is detected, the question of termination of pregnancy for medical reasons is raised, but the final decision on this is made by the parents. Molecular genetic techniques of prenatal diagnostics can confirm diastrophic dysplasia in the fetus even before the beginning of the second trimester, the material for the study is obtained by biopsy of chorionic villi or aminocentesis. The use of such techniques is especially relevant when parents are presumably among the carriers of the pathological form of the SLC26A2 gene (the disease was manifested in blood relatives) or when genetic methods have proven that both parents are heterozygous for the mutant form of SLC26A2 – in such cases, the probability of having a child with diastrophic dysplasia is 25%.