Geleophysic dysplasia is a hereditary disease caused by a violation of cellular growth and development, as well as the functioning of some components of connective tissues. The symptoms of the disease are the characteristic appearance of the face (“happy”), low height, shortened limbs, hypertrophy of muscles, difficulty in movement in the joints. Diagnosis of heliophysical dysplasia is made on the basis of the patient’s current status, the study of his hereditary history, genetic studies. There is no specific treatment for pathology, sometimes surgical operations are performed to correct heart valve defects.
Geleophysic dysplasia is a very rare genetic pathology, which is characterized by numerous malformations, small stature, and a characteristic “happy” facial expression. The incidence of this disease has not been determined, since it is diagnosed extremely rarely, two types of pathology have been identified, inherited both autosomal recessive and autosomal dominant. Recessive type of heliophysical dysplasia is more common. The “happy” facial expression of such patients is due to the upturned corners of the mouth and a thickened upper lip – this is reflected even in the name of the pathology, which translates from Greek as “happy nature”. The classification of heliophysical dysplasia as a genetic disease is currently the subject of scientific debate, since the pathology has signs of both lysosomal accumulation disease and features of impaired growth and differentiation of individual tissues.
After a full study of heliophysical dysplasia and its genetic and molecular foundations, it was long believed that mutations in the ADAMTSL2 gene located on the 9th chromosome were the only cause of this condition. It encodes a protein of the same name that controls, among other things, the activity of the transforming growth factor. The latter takes a direct part in the processes of growth and differentiation of cells of many tissues, there are indications of its important role in apoptosis. As a result of the ADAMTSL2 mutation, a protein with a defective structure appears, unable to fully perform its functions, which leads to the development of heliophysical dysplasia. Otherwise, the pathogenesis of this disease, in particular, the cause of the formation of lysosomal vacuoles in the cells of the trachea, lungs, and gastrointestinal tract, remains unknown. Mutations of the ADAMTSL2 gene are inherited by an autosomal recessive mechanism.
In recent years, through the methods of modern genetics, it has been possible to identify another type of geleophysic dysplasia with autosomal dominant inheritance. It is caused by a mutation of the FBN1 gene, which is localized on the 15th chromosome. The product of its expression is a protein of connective tissues – fibrillin-1, which is located in the epidermis, dermis, zinc ligament of the eye and some other organs. In addition, the role of this protein as a “landing pad” and reservoir of numerous factors of cell growth and differentiation was revealed. Apparently, a defect in the structure of fibrillin-1 arising from a mutation of the FBN1 gene makes it difficult to connect it with these biologically active substances, which causes the development of heliophysical dysplasia. In modern clinical practice, cases of the disease associated with ADAMTSL2 mutations are classified as type 1, and those caused by a defect in the FBN1 gene are classified as type 2. geleophysic dysplasia type 1 occurs many times more often relative to the second type of this pathology.
As a rule, at the birth of a child with geleophysic dysplasia, there are no deviations in body weight, head circumference and other physical indicators. The first symptom that occurs a few months after giving birth is a lag in growth from peers. Over time, significant deviations from the normal age norm are becoming more pronounced – there are cases when patients with heliophysical dysplasia at the age of two years had a body weight of only 5 kg, while their birth weight was 3500 grams. But sometimes the lag in physical development may not reach such significant values and remain at the level of the lower limit of the age norm.
With age, other symptoms of geleophysic dysplasia begin to manifest themselves – the face acquires characteristic features (a smiling mouth, a mongoloid cut of the eyes), a relative shortening of the limbs becomes noticeable. The proximal phalanges of the fingers are wide, contractures of the interphalangeal joints often occur. The skin is dense, in places painless thickenings are determined on it. With geleophysic dysplasia, it is also possible to have symptoms of heart valve damage – cyanosis, shortness of breath, low blood pressure and a number of others. Hepatomegaly is present in almost every case of the disease and can be caused by both primary liver damage and stagnation of blood during the development of heart failure.
The diagnosis of heliophysical dysplasia is made on the basis of the patient’s examination data, the study of his anamnesis, liver and heart studies, genetic analyses. Sometimes a biopsy of tracheal or liver tissues can also be performed, followed by histological examination. The examination reveals the characteristic appearance of the patient with geleophysic dysplasia, a “happy” facial expression, low height, possible muscular hypertrophy. Physical examination reveals an enlargement of the liver, with auscultation of the heart, it is possible to detect noises caused by stenosis of the aortic, mitral or pulmonary valves. At an older age, secondary changes in the heart caused by these disorders can also be detected.
Histological examination of tracheal or liver tissues is performed in controversial cases and when it is impossible to conduct genetic and molecular studies. At the same time, with geleophysic dysplasia, a large number of vacuoles of lysosomal origin are observed in cells. Sometimes they can also be detected in macrophages, which allows not to perform an invasive biopsy, but simply to examine the blood. A geneticist can perform direct sequencing of the ADAMTSL2 and FBN1 genes in order to detect mutations. Thus, not only the diagnosis of heliophysical dysplasia can be proved, but its type can also be determined – this is important, since different types have different inheritance mechanisms. Also, genetic methods can be used to identify the carrier of a pathological gene (with type 1 geleophysic dysplasia) or to carry out prenatal diagnosis of this condition.
Treatment and prognosis
There is no treatment for heliophysical dysplasia, only palliative and symptomatic therapeutic measures are possible. Experimental therapy with the use of growth hormone and some other growth factors has not yielded tangible results to date. In some cases, surgical intervention may be required to correct stenosis of the heart valves, reduce the severity of joint contractures. The prognosis of heliophysical dysplasia is most often unfavorable, it largely depends on the severity of cardiovascular disorders, in some cases, a fatal outcome may occur at an early age from heart failure.