DiGeorge syndrome: symptoms, diagnosis, treatment

Classic DiGeorge syndrome has been described in patients with a characteristic phenotype, including heart defects, facial skeleton, endocrinopathy and thymic hypoplasia. The syndrome can also be accompanied by other developmental anomalies.

The pathogenesis of the syndrome of DiGiorgi

The majority of patients with the DiGJ syndrome phenotype had a characteristic hemizygotic chromosomal aberration in the form of deletion of 22qll.2. This chromosomal abnormality is among the most common in the population (1: 4000). Further studies have shown that deletions in the 22qll.2 region lead to different clinical variants of the syndrome. Immunological defects range from complete thymus aplasia to the SCI clinic (0.1% of all aberrations) to almost normal immune function.

In addition to the most frequent aberration of 22qll.2, the phenotype of the syndrome of DiGeorge is revealed in patients with a 10p13-14 deletion (2% of all cases), as well as in newborns with alcoholic fetopathy, maternal diabetes, isotretinoid fetopathy. In connection with this disease in the main group of patients it was decided to call the syndrome DiGiorgi with a deletion of 22qll.2.

In addition, the phenotypic manifestation of the deletion of 22qll.2 in many patients is called cyclo-cardiofacial syndrome or kovotrunkal facial anomaly. These syndromes do not include immunological defects.

To date, the gene responsible for the main defects of the syndrome of DiGeorge has not been found, but several candidates are located on the 22 chromosome. Many of the structures that are damaged in the 22qll deletion syndrome are derived from the brachiocephalic apparatus derived from the cells of the ganglionic plate. It is assumed that the inconsistency of the gene (s) encoding the transcription factors expressed on the mesoderm and endoderm cells can underlie the development of the DiGeorge syndrome. If they are absent, there is no proper migration of the cells of the embryonic leaflets during the formation of the neural tube, thymus, heart and large vessels.

Symptoms of the syndrome DiGiorgi

The so-called "full" syndrome DiGiorgi with pronounced immunological anomalies is extremely rare. In this regard, most patients with the syndrome in the first place fall into the field of view of specialists of other specialties, first of all, cardiologists.

The main clinical manifestations of the syndrome of DiGeorge are:

• Defects of the heart and large vessels (open arterial duct, anomalies of the aortic arch, tetralogy of Fallot and its variety, transposition of large arteries, right aortic arch, coarctation of the aorta, aberrant subclavian arteries). Vices of large vessels are often combined with heart defects (aplasia or atresia of the tricuspid valve, defects of the interventricular and interatrial septums).
• Hypocalcemic convulsions as a consequence of hypoplasia of parathyroid glands and parathyroid hormone deficiency.
• Deficiency of growth hormone.
• Anomalies of the facial skeleton: gothic sky, crevices of the face, broad bridge of the nose, hypertelorism, fish mouth, low set ears with an underdeveloped curl and pointed top.
• Ophthalmologic pathology: retinal vascular pathology, anterior chamber dysgenesis, coloboma.
• Anomalies in the structure of the larynx, pharynx, trachea, inner ear and esophagus (laryngomalacia, tracheomalacia, gastroesophageal reflux, deafness, swallowing disorders).
• Anomalies of teeth: late eruption, enamel hypoplasia.
• Anomalies of the central nervous system: myelomeningocele, atrophy of the cortex, cerebellar hypoplasia.
• Renal developmental defects: hydronephrosis, atrophy, reflux.
• Skeletal anomalies: polydactyly, absence of nails.
• Malformations of the gastrointestinal tract: atresia of the anus, anal fistula.
• Delayed speech development.
• Delayed motor development.
• Psychiatric pathology: syndrome of hyperactivity, schizophrenia.
• Immunological disorders.

As mentioned above, the degree of immunological disorders varies widely. For some patients, a combined immunodeficiency clinic is characterized, with severe viral infections (disseminated CMV, adenovirus, rotavirus infection), pneumonia. For the majority of patients, life-threatening opportunistic infections are not characteristic, but they have recurrent otitis and sinusitis, in part due to abnormalities in the structure of the facial skeleton.

In the presence of severe T-cell deficiency, autoimmune diseases (cytopenia, autoimmune thyroiditis), and an increased risk of oncological diseases are common in patients with DiGeorge syndrome.

The characteristic immunological manifestations of the complete form of the syndrome are a significant decrease in the number of circulating CD3 +, CD4 +, CD8 + cells and a sharp decrease in their proliferative activity induced by mitogens and antigens. The number of B and NK cells is normal. As a rule, the response to polysaccharide antigens is violated. Concentrations of serum immunoglobulins are in most cases within normal limits, however, in some patients, various violations are detected from selective IgA deficiency to agammaglobulinemia.

Treatment of the syndrome DiGiorgi

According to its clinical manifestations and life expectancy of patients, the full form of the syndrome of DiGeorge is comparable to SCID. There are single descriptions of bone marrow transplantation in patients with complete DiGJ syndrome, however, considering the mechanism of the syndrome development, in which the maturation of T cells is disrupted due to the absence of thymus epithelium, transplantation for such patients is not always effective. Justified for patients with the full form of the syndrome is transplantation of epithelial tissue of the thymus. After transplantation of epithelial tissue of the thymus, restoration of the quantity and functional activity of T cells was noted.

Patients with partial immune disorders often need the appointment of prophylactic antimicrobial and antiviral therapy.

In the case of a decrease in serum immunoglobulin concentrations, substitution therapy with intravenous immunoglobulin is carried out. To correct developmental anomalies, surgical treatment is performed.

Forecast

The prognosis and quality of life of patients with DiGeorge syndrome often depends on the severity and degree of correction of cardiological and endocrinological, and not immunological defects.