Proteus' syndrome, or partial gigantism

A rare disease - Proteus syndrome - is a genetic multi-system pathology with pronounced clinical manifestations, namely: with selective gigantism, defeat of the blood and lymphatic system.

The first mention of the syndrome belongs to Michael Cohen - dated 1979. Four years later, in Germany, pathology received its current name - Proteus' syndrome, after the name of the ancient Greek deity Proteus, the many-faced.

Often, Proteus's syndrome is mistakenly diagnosed as a hamartomatous disease in the form of neurofibromatosis, which is transmitted autosomally dominantly.

Other names of Proteus syndrome: multifaceted disease, human elephant disease, partial giantism syndrome.

[1], [2], [3], [4], [5]

Epidemiology

Proteus' syndrome is considered an extremely rare pathology, since only about two hundred such cases have been found in all time. Such statistics make it possible to assert that the syndrome occurs in less than 1 case per 1 million newborns.

[6], [7], [8], [9]

Causes of the proteus' syndrome

The reason for the development of the Proteus syndrome is a certain gene mutation. We all know that the human body has a large number of DNA-chains, which are transmitted to us from the parents. But sometimes during the embryonic development there is some genetic failure, which leads to the emergence of congenital genetic diseases.

Proteus' syndrome is found with the altered ACT gene: this protein is responsible for the rate of cell growth in the body. If a person is healthy, then his ACT gene is in an inactive state. In patients with Proteus' syndrome, this gene is active and accelerates the process of cell growth.

The severity of the manifestation of pathology depends on which in the pre-natal stage the mutation of the gene took place. The earlier this stage was, the more serious the Proteus syndrome would be.

At the moment, scientists are working on such issues:

• How can the mutation of one gene affect the growth rate of absolutely different human tissues?
• What determines the selective growth of tissues - why do some patients have hypertrophies of the skin, while others have bones and / or vessels?

[10], [11], [12], [13], [14], [15]

Risk factors

The exact factors that influence the development of Proteus' syndrome are unknown. However, scientists have identified a number of factors that could theoretically contribute to the appearance of such a pathology in a child:

• unplanned conception;
• absence of medical pregnancy control;
• viral diseases in a pregnant woman;
• use of illicit drugs in pregnancy, as well as chronic and acute intoxication;
• smoking and drinking alcohol during pregnancy;
• addiction;
• insufficient intake of vitamins and other essential substances in the body of a pregnant woman;
• bad ecology, radiation, occupational hazards.

[16], [17], [18],

Pathogenesis

The pathogenesis of Proteus' syndrome is not fully understood. It is only known that the development of pathology results in the mosaicism of somatic cells - an anomaly of combining sex chromosomes with a dominant gene, which has not been determined to date.

Nevertheless, this theory is also questioned by some scientists, since there were single cases of minor signs of the disease in the parents of the affected individuals.

The combined existence of hyper and hypoplasia in Proteus syndrome suggests a possible embryonic somatic recombination, which causes the appearance of at least three cellular subspecies: normal, hypertrophic and atrophic cellular structures.

[19], [20], [21], [22]

Symptoms of the proteus' syndrome

Typically, people with Proteus syndrome, in infancy do not differ from other children: pathological changes begin to manifest over the years. To diagnose Proteus' syndrome is very difficult at first, since the first signs of the disease in each patient may differ. The only characteristic feature of the disease is the growth of tissues. At the same time any tissue of the human body can grow: bone, muscle, fatty tissue, as well as vessels of the circulatory and lymphatic system. Sprawl can affect almost any organ. True, a larger percentage of overgrown tissue is fixed on the limbs and in the head region.

Proteus' syndrome directly affects the decrease in the life expectancy of the patient, and this is due to frequent problems with the blood vessels. Among such problems, thromboembolism, thrombosis, etc. Are common. No less common are tumor processes and lesions of the endocrine system.

By itself, the syndrome has no effect on reducing the intellectual level of the patient, but the pathological proliferation of nervous tissue can provoke a significant lag in mental development.

The first signs of the syndrome can occur in children, starting with 2 or 4 years. Usually these are the symptoms:

• an increase in the size of one of the limbs;
• an increase in the size of individual bones;
• local compaction and thickening of skin areas - for example, in the face, palms, feet;
• development of tumor processes.

Complications and consequences

• Hypertrophic asymmetry of the arms, legs and fingers, hemygiperplasia, megalospondylodisplasia.
• Curvature of the spinal column.
• Increased language, abnormal growth of unchanged skull bone (hyperostosis), microcephaly.
• Vascular defects, lipomas and nevi (connective tissue, epidermal).
• Local invasive defects of adipose tissue or vessels.
• Cystic formations in the lungs.
• Formation of thrombi within deep vessels, pulmonary thromboembolism.
• Cystic formations in the appendages, benign tumors of the parotid salivary glands, some types of oncology.
• Strabismus.
• Defects of the dentition.
• Disorder of intellectual development, problems with progress.

[23], [24], [25], [26], [27]

Diagnostics of the proteus' syndrome

It is almost impossible to diagnose Proteus' syndrome at the initial stage, since the main diagnostic criteria are the characteristic symptoms of the disease:

• proliferation of tissues;
• disproportionate hypertrophy of the limbs;
• an increase in organs or parts of the body;
• curvature of the spine due to disproportionate development of the vertebrae;
• cystic abnormalities;
• lipomas, defects of the circulatory and lymphatic systems.

Analyzes to confirm the diagnosis of Proteus syndrome are not carried out. Be sure to monitor the coagulability of the blood, because the disease is characterized by thrombosis and thromboembolism.

Instrumental diagnosis may include X-ray examination, magnetic resonance imaging, computed tomography, angiography, encephalography, etc.

• X-rays can assess the condition of the curved spine, as well as changes in bone tissue of the extremities or fingers.
• Tomographic methods of investigation help to assess the state of the cranial cavity, reveal defects in the development of the brain, detect vascular anomalies, tumors, cysts, etc.
• Encephalography is prescribed in the presence of convulsions, to determine their cause.
• Angiography and Dopplerography allows to establish the presence of thrombosis and embolism of deep vessels.

Sometimes with Proteus syndrome, especially in the presence of tumor processes, doctors prescribe a histological examination with a preliminary biopsy.

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Differential diagnosis

Differential diagnosis of Proteus syndrome is carried out with the following diseases:

• with the syndrome of Klippel-Trenone-Weber;
• with neurofibromatosis;
• with encephalocraniolipomatosis;
• with a syndrome of lipomatosis-hemihyperplasia.

[29], [30], [31], [32],

Treatment of the proteus' syndrome

Proteus' syndrome is considered an incurable disease. However, early diagnosis of the disease can successfully overcome the main signs of pathology and avoid complications. For example, when the vertebral column is curved, with excessive growth of bone tissue, if the limb length does not match, the patient is asked to use special orthopedic devices.

If the disorder is observed in the hematopoiesis system, or the growth of tumor processes is detected, then the patient with Proteus syndrome should be under lifelong medical supervision.

The drug treatment of Proteus' syndrome consists only in prescribing symptomatic drugs. These include analgesics (Ibuprofen, Ketolong), diuretics (Furosemide, Lasix), anticoagulants (Heparin, Fragmin, Fondaparinux, Tinzaparin), vasopressors (Dopamine, Dobutamine), thrombolytics (Urokinase, Streptokinase, Alteplase).

Medications allowed for Proteus' syndrome

	Dosing and Administration	Side effects	special instructions
Ibuprofen	With pain take 600 mg 2-3 times a day.	Reception can be accompanied by nausea, dyspepsia, pain in the stomach.	Ibuprofen is not used for violations of the hematopoietic function.
Lasix	With swelling take 20-80 mg per day, with a possible further increase in dosage.	Possible lowering of pressure, weakness, pain in the head, thirst, allergy.	Reception of the drug should be combined with compensation of electrolyte disorders.
Tinzaparin	It is used as an anticoagulant according to individual treatment regimens.	With prolonged treatment, it is possible to develop hemorrhagic complications.	The drug is used, constantly monitoring the degree of clotting of the blood.
Dobutamine	The drug is used according to individually selected schemes.	Long-term treatment can cause arrhythmia, changes in blood pressure.	When treating the drug, it is necessary to monitor heart rate, blood pressure, diuresis.
Streptokinase	The drug is administered intravenously drip, at an average dosage of 250,000 IU in 50 ml of saline at a rate of 30 cap / min.	Possible hyper-reaction to protein: pain in the head, nausea, fever.	Treatment is carried out with control of blood coagulation and fibrinogen levels.

Vitamins

The diet of a person suffering from Proteus syndrome should include vitaminized and balanced meals. In addition, periodically you can take additional vitamins - mainly to strengthen blood vessels, the heart, to improve the condition and structure of cells and tissues.

• Riboxin - favorably affects metabolic processes and hepatic function
• Aspartame - prevents problems with the cardiovascular system.
• Doppelherz - contains potassium necessary for the sick organism and useful Omega-3 acids.
• Sophora is a drug for preventing vascular and cardiac diseases.
• Ascorutin - a drug to maintain the normal state of the vascular wall, for the prevention of thrombosis.

Vitamin preparations are usually prescribed individually, as some patients may be intolerant to a particular component.

Physiotherapeutic treatment

Physiotherapy with Proteus syndrome is usually aimed at maintaining the function of the cardiovascular system, improving the coronary and peripheral circulation. With the improvement of blood circulation, the level of oxygen transportation increases, the processes in the central nervous system and the autonomic nervous system are facilitated, and neuroendocrine and immune responses are normalized.

To improve the condition of the patient with Proteus syndrome, various physiotherapy methods can be used, depending on the dominant manifestation of the disease.

Contraindications to physiotherapy may include:

• unstable angina;
• severe circulatory failure;
• severe heart rhythm disturbances;
• aneurysm;
• feverish conditions;
• oncology and suspicion of similar processes;
• thromboembolism;
• infarct-pneumonia.

The choice of a specific procedure for the Proteus syndrome depends on the severity of the functional disorder of the cardiovascular system, the state of the nervous and neurohumoral system of regulation of blood circulation, and also on the presence of other malfunctions in the body.

Alternative treatment

To improve the quality of blood in Proteus syndrome, it is recommended to regularly drink beverages from berries of viburnum, sea buckthorn, cranberries, blueberries.

To prevent thrombosis in Proteus syndrome, teas and infusions are considered useful on the basis of mother-and-stepmother, pubescent, astragalus, comfrey, raspberry leaves. Brewed 1 tbsp. L. Herbs in ½ liter of boiling water, insist under the lid before cooling down. Such medicine is drunk on half a glass three times a day.

A huge benefit is the famous ginger tea: it dilutes blood and improves blood circulation, prevents the accumulation of toxins. To make medicinal ginger tea, a slice of ginger root is rubbed on a grater and poured with boiling water, it is insisted 20 minutes. After cooling into the drink, add a little honey and / or lemon. To improve the lymph flow in such tea, you can add a pinch of cinnamon.

If the affected tissues formed edema, then use this method: to the affected areas apply the sliced tomato slices: after 3-4 hours, the lobules are replaced with fresh ones.

An example of treatment of Proteus syndrome with the help of mummies:

• dissolve 8 g of mummy in 500 ml of boiled water;
• drink within 10 days of 1 tbsp. L. In the morning on an empty stomach.

The course of treatment can be repeated after 5 days. In total, 4 courses are recommended.

Affected areas can be treated with ointment, which is a 20% diluted mummy in a mixture with petroleum jelly.

[33], [34], [35], [36], [37], [38]

Herbal Treatment

• The rhizome of ginseng is taken before meals inside - 20 drops of tincture on alcohol three times a day, or in tablets of 0.15-0.3 g three times a day. Duration of admission is ½-1 month.
• Prepare a mixture of 20 grams of buckthorn bark, 80 grams of birch leaves, 100 grams of willow bark. Prepare an infusion of 1 tbsp. L. Of the resulting mixture and 250 ml of boiling water. The medicine is drunk 2 glasses daily.
• Take a tincture of garlic in the amount of 20 drops to 3 times a day, or tincture of onion - 25 drops three times a day, for a month.
• With edemas, herbal teas are made on the basis of birch leaves, horsetail herbs, parsley root, juniper berries, dandelion roots, hips.

Homeopathy

To date, many medical specialists have recognized the effectiveness of homeopathic medicines in the treatment of various, including chronic, diseases. There are also homeopathic remedies that can help, if not cure, then significantly weaken the manifestations of such a disease as Proteus's syndrome.

For example, Lymphomyosot is a complex homeopathic preparation of German manufacture that performs several useful functions in the body:

• removes toxic substances, products of tissue decay and metabolism;
• stops the pathological proliferation of tissues;
• prevents formation of edema.

Lymphomyosot can be purchased in pharmacies in the form of drops, tablets or injection solution. The drug is recommended for use on the prescription of the doctor three times a day (tablets or drops), or 1-3 times a week (intramuscular or subcutaneous injection). The course of treatment with Lymphomyosot can last for a long time, if necessary up to several months.

In order to enhance the effectiveness of the drug, it can be combined with other homeopathic remedies. Most often use such drugs: conium, thuya, calcium fluoride. Less often, and according to the testimony - Solanum Tuberozum, succinum, apis and tropeolum.

In addition, potentiated Ceylon agents (mitotic cell preparation regulators), epidermal growth factor (EGF) agents, fibroblast growth factor (FGF) agents have been actively used during the last decade.

The listed drugs are practically devoid of unpleasant side effects, but can significantly improve the condition of patients with Proteus syndrome.

Operative treatment

Some types of tissue proliferation in the Proteus syndrome require prompt correction. For example, with jaw deformities,

• surgical orthodontic correction of occlusion;
• the building of individual teeth, the formation of the right dentition;
• maxillofacial interventions, etc.

In the presence of skin and subcutaneous growths, surface hemangiomas, their laser removal or cryodestruction can be used. Cystic formations and tumors (including internal ones) are removed by surgery.

• The operation may be required with a progressive curvature of the spine, with excessive lengthening of the fingers, etc.
• Operative intervention is justified in the presence of growths that interfere with the normal function of breathing, vision, hearing, and also those that are located in the field of vital organs.
• Necessarily removed growths prone to a rapid increase.

Some operations with Proteus' syndrome are performed for aesthetic reasons - for example, if the growth of the tissue is found in the face or head region.

Prevention

The scientists formulated the so-called "10 commandments" for women, on the prevention of birth defects in the future child, including the prevention of Proteus syndrome. Such "commandments" consist of the following recommendations:

1. A woman who is in reproductive age, is sexually active and is not protected, should be ready to be able to become pregnant at any time.
2. Pregnancy should always be properly planned, and it is desirable to do it at the age of 30-35 years.
3. During the entire period of gestation, it is necessary to visit the doctor and monitor the course of pregnancy and the condition of the fetus.
4. Before the onset of pregnancy, it is advisable to get vaccinated against rubella. When pregnancy should beware of contact with people who suffer from viral diseases - not to visit public places during epidemics, wash their hands with soap on arrival from the street, etc.
5. Categorically, one should not take any medication during pregnancy without the permission of a doctor.
6. You can not drink alcohol, smoke and take drugs.
7. In the continuation of the previous paragraph: places and premises for smoking should be avoided.
8. It is necessary to eat a balanced and balanced diet, to consume enough plant food.
9. If possible, you should just rest during pregnancy, do not overload the body with physical labor.
10. For any doubt or suspicion, consult a doctor.

[39], [40], [41]

Forecast

All sorts of complications - for example, abnormal central nervous system function, rapidly growing spinal curvature, thrombosis, internal organ damage - can adversely affect the quality and life expectancy of patients with diagnosed Proteus syndrome.

The earlier this diagnosis is established, the more likely the patient to avoid many complications. And timely preventive and curative measures can positively affect the quality of life, increase its duration.

In general, Proteus' syndrome in patients who do not need surgical treatment does not prevent the conduct of a relatively active lifestyle.

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