Kouden's disease – a genetic disease as which main display serves formation of benign tumors of internals is also raised the frequency of emergence of malignant new growths. Multiple gamartoma and cysts are formed in digestive tract, a mammary gland, bodies of reproductive system. Diagnosis of a disease of Kouden partially is based on studying of the present status of the patient, but the most exact result provides the genetic analysis. Specific treatment does not exist for today, only symptomatic therapy including surgeries for removal of good-quality new growths is used.
Kouden's disease (a syndrome multiple gamarty) – rare hereditary pathology at which processes of braking of pathological growth of fabrics are broken and because of it there are benign tumors and there is a risk of development of malignant new growths. For the first time the syndrome was described in 1963 by the American doctors M. Kennes, L. and M. Dennis, the name comprises a surname of the first described patient with this disease. Kouden's disease meets frequency of 1:1000000 people, with equal degree of probability affects both men, and women. At the same time at female persons the disease is observed in easier form. The gene which defect leads to development of a disease of Kouden (PTEN) can have also other mutations leading to such diseases as a syndrome of Banayan-Riley-Ruvalkaba, and also a disease of Lermitt-Duklos. Therefore doctors geneticists quite often unite them in one group – the PTEN associated syndromes of gamartomny tumors.
Is the main etiology of Kouden mutations in PTEN gene located on the 10th chromosome, it codes unique protein-phosphatase. This protein is capable to influence the proteins and lipids containing phosphates in an inozitolny ring, chipping off phosphatic group. Many of the substances which are a substratum for PTEN phosphatase represent secondary intermediaries in information transfer in a cage. This way (which is called on the main PI3K/AKT/mTOR components), in addition, allows a cage to avoid apoptosis even at direct impact on the corresponding receptors on a membrane. Such process is implemented in many types of malignant and benign tumors. The gene of PTEN blocks this way, thereby showing activity of a key antioncogene, but in the presence in it defects various pathologies including Kouden's disease develop.
Transfer of the mutations leading to Kouden's disease is carried out on the autosomno-prepotent mechanism, quite often violations of a gene have the germinalny nature – arise in gametes of parents in the course of their formation. Because of violation of braking of a PI3K/AKT/mTOR-way protective antineoplastic mechanisms of an organism become weakened therefore the probability of development of numerous new growths increases. Besides, the specified way plays an important role in functioning of heart and central nervous system therefore at Kouden's disease violations of intellectual development are often observed. Besides a classical picture of a syndrome, there are Kouden-like violations caused by mutations of other genes. Methods of modern genetics determined only some of them (for example, SDHD and SDHB) which, also as well as PTEN gene, show antionkogenny activity.
Symptoms of a disease of Kouden
The symptomatology of a disease can be shown at any age - both in the early childhood, and in old age. Besides, the clinical picture of a disease Koudena is quite variable and not always begins with education gamarty or other types of benign tumors. For example, the pediatrician can diagnose a delay of mental development for the child, and specific displays of a genetic disease can arise only at adult age. As the first symptoms of a disease of Kouden a miopiya, violations of formation of maxillofacial area, pathology of teeth, frequent inflammatory diseases of the top airways can also act (sinusitis). All this does diagnosis of a disease quite difficult because of big variability of the first manifestations and time of their demonstration.
The Simptomokompleks of a disease of Kouden at full development of a disease includes damages of a thyroid gland, formation gamarty in digestive tract. Integuments of the patient thin, dryness of mucous membranes and formation of leukoplakias on them is often observed. At women with Kouden's disease at young age reveal fibrous and cystous mastopathy, the cystous giperplaziya, an underdevelopment of the lacteal courses is sometimes possible. The hypoplasia of a uterus and instability of a menstrual cycle which is coming down to periodic amenoreyam of various duration is often observed. From the central nervous system, besides a delay of intellectual development, the incoordination of movements, an ataxy often comes to light. At Kouden's disease are frequent violation of the speech (dislaliya) which reasons, however, are most often caused by defects of formation of teeth, language, a soft palate.
In a mouth, besides violation of formation of teeth, often there are papillomatozny educations on mucous membranes. Premature loss of teeth is characteristic, language is increased, red color with a non-uniform surface. In hard cases of a disease of Kouden formation of cysts and tumors in a liver, kidneys, elements of the musculoskeletal device is possible. The thorax is often hollow, asymmetric, sometimes there is a backbone curvature. Formation of genitalia at Kouden's disease occurs without violations, in some cases preservation of genital function is observed. Among disease complications the greatest threat is posed by the malignant new growths arising in various bodies initially or as a result of a malignization gamarty and cysts.
Diagnostics and treatment of a disease of Kouden
It is not always possible to reveal Kouden's disease when studying the present status of the patient because of considerable variability of its manifestations which, besides, can begin to develop at any age. Also not always studying of the hereditary anamnesis as in some cases mutations of a gene of PTEN have the germinalny nature will help and are absent at parents and the patient's relatives. In the presence of multiple gamarty digestive tract, violations of formation of teeth, fibrous and cystous mastopathy and other displays of a disease of Kouden it is necessary to make genetic diagnosis of a disease. Only the sekvenirovaniye of the sequence of a gene of PTEN can reveal existence of a mutation and with guarantee confirm existence or absence of a disease of Kouden. Differential diagnostics is made with other PTEN associated syndromes, and also Klouden-like diseases caused by mutations of other genes.
Specific treatment of a disease of Kouden does not exist today, methods of gene therapy which have to allow "to replace" the struck PTEN gene at present are studied on laboratory animals. Symptomatic treatment is performed by medical experts of various profiles – the stomatologist makes correction of teeth and if necessary prosthetics, the surgeon deletes gamartoma and other opukholevidny educations. When diagnosing a disease of Kouden at early age pediatricians and children's psychologists can reduce expressiveness of violations of intellectual development. Gynecologists together with surgeons treat pathology of mammary glands and internal female genitals. Reasonable therapy and continuous monitoring of a state allow to improve considerably quality of life of the patient, in time to reveal and treat the arisen complications.
Forecast and prevention of a disease of Kouden
The forecast at Kouden's disease in most cases uncertain as expressiveness and character of symptoms of pathology have considerable variability. Violations of intellectual development are observed only at a half of patients, the others keep the satisfactory level of intellectual activity. The main danger at Kouden's disease is made by probability of a sdavleniye of a gamartomama and other benign tumors of important nervous and vascular structures, and also risk of development of malignant new growths. Therefore regular monitoring of a condition of the patient at the oncologist and the doctor geneticist is necessary. These precautionary measures will help to reveal in due time arisen complications, their treatment at early stages in most cases can improve the forecast of survival of the patient considerably.