Proteus syndrome is a disorder in which there is excessive skin growth and unusual bone development, often with tumors on more than half the body. An extremely rare condition, it has only affected just over 200 people.
Affected organs and tissues tend to overgrow. Barely noticeable at birth, it appears between 6 and 18 months of age. There is a risk of premature death due to vascular malformations.
Proteus syndrome is not passed on from either parent, nor is it caused by environmental factors before or during pregnancy. Appears as a result of a mosaic mutation of the AKT1 gene. Diagnosis includes genetic testing of mosaic, sporadic occurrence, progressive course.
A drug called Rapamycin is used effectively to treat this disease.
Other names:
- Hemihypertrophy and macrocephaly;
- Partial gigantism of the arms, legs, nevi, hemihypertrophy.
Proteus syndrome is characterized by excessive growth of a body part. Overgrowth is usually asymmetrical, affecting the right and left sides differently.
Newborns show little or no signs of the disorder.
Leads to differences in appearance over time, an increased risk of blood clots and tumors.
Some have neurological abnormalities, including intellectual disability, seizures, vision loss, and distinctive facial features.
The condition is not inherited and occurs as a random mutation early in pregnancy. AKT1 affects only part of the body's cells. Therefore, only part of the body is affected and people with Proteus syndrome may be affected differently.
Treatment of the disease often requires a team of specialists with knowledge of the wide range of features and complications of the condition.
Canadian geneticist Michael Cohen Jr., DMD, PhD, first described the condition in 1979, and German pediatrician Hans Rudolf Wiedemann named the disease in 1983 after a Greek god who could transform his form.
Symptoms
The table lists the symptoms that people with this disease may have. People with the disorder may not have all of the symptoms listed.
| Medical terms | Other names |
80%-99% have these symptoms | |
| Abnormal vertebral shape | |
| Incorrect distribution of subcutaneous adipose tissue | |
| Arteriovenous malformation | |
| Breast asymmetry | |
| Cachexia | Exhaustion |
| Capillary hemangioma | |
| Decreased muscle mass | Underdeveloped muscles |
| Disproportionate height | |
| Epidermal nevus | |
| Irregular hyperpigmentation | |
| Kyphosis | Round back |
| Lipoma | |
| Asymmetry of the lower and upper limbs | |
| Lymphangioma | |
| Macrodactyly | Broken finger |
| Melanocytic nevus | |
| Scoliosis | Abnormal curvature of the spine |
| Subcutaneous node | Hard mass under the skin |
| Violation of the vascular network of the skin | |
30%-79% show signs | |
| Abnormal pulmonary lopination | |
| Bronchogenic cyst | |
| Hyponosis of the vessels of the leg | |
| Dolichocephaly | Tall, narrow skull |
| Digital syndactyly | Spliced fingers |
| Generalized hyperkeratosis | |
| Hypertelorism | Wide-set eyes |
| Lymphedema | |
| Macrotia | Big ears |
| Coffee stains | |
| Pulmonary embolism | |
| Round face | |
| Thrombophlebitis | |
| Visceral angiomatosis | |
5% -29% of people have | |
| Anomaly of tooth enamel | |
| Retinal pigmentation disorders | |
| Overdeveloped metacarpal bones | Long Bones |
| Antevered nostrils | Nose up |
| Arterial thrombosis | Blood clot in an artery |
| Buphthalmus | Enlarged eyeball |
| Carious teeth | Tooth decay |
| Cataract | Clouding of the eye lens |
| Central heterochromia | |
| Chorioretinal coloboma | Congenital defect. A hole in the inner layer of the back of the eye |
| Clinodacty of the fifth toe | Permanent bend of the little finger |
| Craniosynostosis | |
| Flattened nasal bridge | Flat nose bridge |
| Diabetes | |
| Falling finger-shaped cracks | Tilt down between eyelids |
| Enlarged | |
| Exostoses | |
| Facial asymmetry | Asymmetrical face |
| Generalized hirsutism | |
| Generalized hyperpigmentation | |
| Hallux valgus | |
| Heterotopia | |
| Hip dislocation | |
| Intellectual disability | Mental retardation |
| Poor joint mobility | Stiff joints |
| Long face | Vertical facial growth |
| Long penis | Enlarged penis |
| Low set ears | |
| Macrocephaly | Large head circumference |
| Macroorchidism | Big testicles |
| Meningiomas | |
| Metatarsus valgus | |
| Myofibrillar myopathy | |
| Myopia | |
| Narrow internal auditory canal | |
| Lung neoplasm | |
| Thymic neoplasm | |
| Ovarian neoplasm | Ovarian tumors |
| Proptosis | Protruding eyes |
| Ptosis | Drooping upper eyelid |
| Repeated infections | |
| Reduced number of teeth | |
| Kidney cyst | |
| Reticular hamartoma | |
| Seizures | Convulsions |
| Sirenomelia | |
| Splenomegaly | Enlarged spleen |
| Strabismus | |
| Sudden death from heart attack | |
| Testicular neoplasm | Testicular tumor |
| Thick nose alleys | |
| Thymic hyperplasia | Enlarged thymus |
Other symptoms | |
| Deep vein thrombosis | Blood clot in a vein |
| Depigmentation, skin hyperpigmentation | |
| Epibulbar dermoid | |
| Epidermal acanthosis | |
| Facial hyperostosis | Increase in the size of facial bones |
| Hemangioma | Wine stains |
| Hemihypertrophy | Asymmetrical growth |
| Hyperkeratosis | |
| Hypertrophy of the skin of the soles | Thick leather soles |
| Intellectual disability, moderate | IQ between 34 – 49 |
| Kyphoscoliosis | |
| Mandibular hyperostosis | |
| Several liposomes | |
| Nevus | |
| Open mouth | |
| Spinal canal stenosis | Narrow spinal canal |
| Spinal cord compression | |
| Thin Bones | |
| Venous deformity |
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The AKT1 mutation alters the ability of affected cells to regulate their own growth, causing some parts of the patient's body to grow to abnormal or even enormous sizes while others remain normal. The unevenness increases with age and increases susceptibility to neoplasms.
In addition to excessive limbs, the disorder causes many skin lesions, thickening of the soles of the feet. Some patients have neurological complications such as mental retardation, seizures, and vision loss.
Individuals with this disease have a significantly increased risk of developing deep vein thrombosis and pulmonary embolism.
Cause
The gene variant that causes Proteus syndrome occurs spontaneously after conception in only one cell of the developing embryo. As they continue to grow and divide, some have the mutation and others do not. The victims have an altered gene AKT1 only in some, known as mosaicism.
AKT1 encodes a protein that helps regulate cell growth, division (proliferation), and death. A mutation in it disrupts the cell's ability to regulate its own growth, allowing it to grow and divide abnormally.
The mutated gene creates an abnormal protein. The mutation is known as "c. 49G>A, p.Glu17Lys.” The gene has an error that creates an abnormally active protein in the body. It is believed that the active protein increases the rate of tissue growth and prevents tissue death. Increased proliferation leads to abnormal growth and increased risk of cancer.
Diagnostics
Diagnosis is based on clinical criteria including three general characteristics and a specific list of symptoms. Mutation AKT1 detected in more than 90% of people meeting diagnostic criteria.
There are three general features that must be present to confirm the diagnosis of Proteus syndrome:
- Mosaic distribution: means that the areas of overgrowth are patchy, with only some parts of the body showing signs of overgrowth and others unaffected.
- Sporadic occurrence: No one in the affected family shares similar traits.
- Progressive development: Excessive development noticeably changes the appearance of the affected parts of the body over time or new areas of damage appear.
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If a person has all three signs in addition to some specific characteristics, doctors consider a diagnosis.
Specific characteristics are grouped into three categories: A, B, C. Diagnosis requires the presence of all three general characteristics and one category A or two category B, three category C.
Category A
Cerebral connective tissue nevus, which is a skin lesion with deep grooves observed on the surface of the brain.
Category B
- Growths caused by excessive growth of cells on the outer layer. (Linear epidermal nevus)
- Asymmetrical, disproportionate growth (at least one of the following):
- Limbs;
- Hyperostosis of the skull;
- Hysterosis of the external auditory canal;
- Megaspondylodysplasia;
- Spleen, thymus.
- Tumors before age 20
- Bilateral ovarian cystadenoma (benign ovarian tumor)
- Parotid monomorphic adenoma (benign tumor of the salivary gland).
Category C
- Abnormal growth or distribution of fat (adipose tissue dysregulation), any of the following:
- Fatty tumors (lipomas);
- Lack of subcutaneous fat (regional lipohypoplasia);
- Vascular malformations (differences in blood vessels, veins, capillaries), including one of:
- Capillary malformation;
- Venous deformity;
- Lymphatic malformation;
- Lunar bullae.
- Facial signs (all of the following):
- Long, narrow head (dolichocephaly);
- Long face;
- Palpebral fissures, slight ptosis;
- Flattened bridge of the nose;
- Wide nostrils;
- Open mouth at rest.
Treatment
Each person with Proteus syndrome has different medical needs that require individualized treatment. Many patients are accompanied by several specialists, such as a geneticist, pediatrician, dermatologist, and others.
A rare genetic disorder that leads to the overgrowth of bone and other tissues.Proteus syndrome is an extremely rare genetic disorder that causes overgrowth of body tissues such as bones. The growth often occurs disproportionately and can seriously change a person's appearance. The condition was named after the Greek god Proteus, who could take on different forms at will.
Symptoms of proteus syndrome
Each person with Proteus is affected differently. Some people may have overgrown limbs, while others experience excessive skull growth. While this condition can affect any part of the body, the most common are bones, fat, and connective tissue. Blood vessels and internal organs may also be affected.Symptoms and features of Proteus syndrome are absent at birth. As the child begins to grow, the condition becomes apparent - usually between 6 and 18 months of age. The condition becomes more severe as the child continues to grow.
Although the specifics of the condition vary, certain symptoms are commonly observed in all patients diagnosed with Proteus syndrome.
General symptoms of proteus syndrome
Three characteristics common to people with Proteus syndrome include:- Some parts of the body, such as the limbs or head, grow rapidly and are disproportionately large compared to other parts of the body. The growth pattern usually occurs in an asymmetrical and "spotted" (mosaic) formation. Which parts of the body are affected will vary from person to person.
- Over time, overgrowth becomes more severe and can change a person's appearance. Over time, a person may experience excessive growth in new areas.
- No one in the person's family has the condition or any symptoms indicating it.
- Noncancerous (benign) tumors
- Abnormal curvature of the spine (scoliosis)
- Fatty growths (lipomas) or areas of tissue loss (atrophy)
- Deformed blood vessels, which increase the risk of blood clots and pulmonary embolism (the most common cause of death in people with Proteus syndrome)
- Thick, rough, raised grooves in the skin, especially in the lower legs (a condition called connective tissue neurosis cerebri, which is almost exclusively seen in people with Proteus syndrome)
People with Proteus syndrome may also have certain facial features, such as a long face with wide nostrils, squinting (strabismus), and drooping eyelids (ptosis). Some studies suggest that people with characteristic facial features associated with Proteus syndrome are more likely to have neurological problems associated with the condition. Although the connection between these two aspects has been noted, it is not yet fully understood.
Causes of proteus syndrome
Proteus syndrome is not believed to be hereditary. Of the several hundred cases in the medical literature, not a single person known to have Proteus syndrome had a child with the condition.Proteus syndrome, however, is caused by a genetic mutation. In 2011, researchers identified the gene responsible for proteus syndrome: AKT1. The gene is involved in how cells grow and divide (proliferation) and can also prevent cells from dying when they should (apoptosis). Because it affects these cellular mechanisms, the gene is also involved in some forms of cancer.
Even though Proteus syndrome is associated with a gene, it does not mean that the parent "gives" the condition to the child. Mutations occur spontaneously (sporadic) and in the early stages of fetal development.
A mutation in the AKT1 gene affects how cells grow, but the mutation will not affect all cells (called mosaicism). This causes some tissues to grow normally, while others develop the growth characteristic of Proteus syndrome.
The specific symptoms a person has and their severity are usually proportional to the ratio of normal to mutated cells they have.
How they mutate and cause disorders
Diagnosis of proteus syndrome
Proteus syndrome is very rare, with only a few hundred cases diagnosed worldwide, and many researchers believe the condition may be overdiagnosed. Other conditions that can cause asymmetric or abnormal growth patterns may be misdiagnosed as Proteus syndrome, meaning the true incidence of the disorder may be even rarer.Doctors use a very specific set of guidelines to make a diagnosis of Proteus syndrome. Understanding the role that gene mutations play in the development of the condition has helped make the diagnostic process more accurate.
Along with diagnostic criteria that include the presence of physical characteristics, signs and symptoms, diagnosing Proteus syndrome usually requires a thorough workup including tissue biopsy, laboratory tests, imaging studies and genetic testing.
Proteus syndrome was not described in the medical literature until 1979. Because the disease is so rare, many doctors have never seen it. Even with strict diagnostic criteria, it can be difficult to correctly diagnose the condition. Proteus syndrome appears to affect men more often than women and occurs in people of all racial and ethnic groups.
One of the most notable cases of Proteus syndrome is that of Joseph Merrick, better known as the "Elephant Man." Throughout his life in the early 19th century, Merrick was thought to have neurofibromatosis. Many decades later, researchers now believe that he actually had Proteus syndrome.
Why the medical mystery "The Elephant Man" has baffled doctors for 100 years
Treatment of proteus syndrome
Does not exist from Proteus syndrome. Each person who has the condition will have different symptoms, and these symptoms will vary in severity. All patients with Proteus syndrome will need to work with a team of healthcare professionals to manage their medical care.Health needs
Some common health needs of people with Proteus syndrome include:- Surgery to remove growths or excess skin
- Dental problems, including malocclusion
- Poor vision, squinting (crossed eyes), or vision loss due to neurological disorders
- Cosmetic procedures to correct areas of the body deformed due to excessive growth
- Monitoring of affected organ systems (kidneys, brain, spine, etc.)
- Mental health, social and educational support
- Referral to specialists who deal with body systems that are more severely affected or that are at higher risk for complications (for example: a vascular doctor who can monitor a person for blood clots, or an orthopedist who can help treat problems related to excessive bone growth)
However, surgery comes with its own risks, especially for patients at risk of developing blood clots, as most with Proteus syndrome do. Because of this risk, deciding when, if at all, to act can be a difficult decision for the clinician.
Other potential problems, although they may not shorten life expectancy, can certainly affect a person's quality of life. Excessive height or growth caused by Proteus syndrome can seriously change a person's appearance. When one or more limbs are affected, a person's mobility can be greatly affected. This, combined with neurological effects, can limit a person's ability to live independently. The social stigma associated with looking "different" can cause emotional distress, anxiety, and depression.
While people with Proteus syndrome usually need a team of specialists to manage their care, as most doctors (such as general practitioners or internists) are unlikely to have encountered such cases earlier in their careers, the management of a person's care is usually supervised. specialist such as a geneticist.
The need for regular care, follow-up care, and close monitoring with specialists will depend on which areas of the body are affected, as well as the severity of a person's symptoms and the progression of the condition.
A word from Health-Ambulance
Because Proteus syndrome is so unusual, it can be difficult to properly diagnose. Once a person has been diagnosed, the primary focus is on managing symptoms (which can range in severity from mild to debilitating and can be physical, medical, and cosmetic) and preventing potentially life-threatening complications (such as pulmonary embolism or blood clots). ).Managing Proteus syndrome can be difficult, but is most successful when a person with the condition has the support of a team of health care professionals, including specialists, genetic counselors and mental health professionals, who can address all aspects of a person's life that have been affected by the condition.
is a rare congenital pathology manifested by abnormal growth of individual parts of the body. Usually there is an increase in the area of the head, arm or leg. Partial hypertrophy is combined with an increased likelihood of developing thrombosis and thromboembolism, the formation of tumors of various structures and localizations. The diagnosis is made based on the results of the examination, X-ray data, CT, MRI, angiography, Dopplerography. Radical treatment has not been developed. Orthopedic devices are used, operations are performed according to indications to improve limb function, facilitate breathing and eating, and surgical removal of neoplasia is performed.
ICD-10
Q87.5 Other congenital anomaly syndromes with other skeletal changes
General information
Proteus syndrome (partial gigantism) is a very rare congenital disease. Approximately 200 cases of this pathology are mentioned in the literature, while experts do not exclude that some patients could suffer from other diseases with similar symptoms. The first description of the syndrome was presented in 1979, but it became widely known after the publication of the work of the German pediatrician Wiedemann in 1983. The name was also suggested by Wiedemann in association with the ancient Greek god Proteus, who was capable of changing his appearance. The disease has a pronounced negative impact on the quality of life of patients, both due to external disfigurement and due to dysfunction of the affected parts of the body. It often causes early death due to the high likelihood of developing tumors and the tendency to thrombosis.
Causes
The cause of the disease is somatic mosaicism, presumably caused by a random mutation of a dominant gene. Some experts question the random nature of the mutation, based on information about the identification of several cases of mild signs of the syndrome in parents of patients. There are studies according to which the pathology is caused by a mutation of the PTEN gene, located in the 10q locus of the X chromosome. However, researchers indicate that mutations of this gene are found in only 20% of patients with Proteus syndrome and are detected in some other diseases characterized by an increased likelihood of the formation of malignant neoplasia. Thus, the genetic basis of the disease has not yet been definitively established.
Pathogenesis
As a result of mutation, three types of cells are formed in certain parts of the body - normal, hyper- and atrophic. In the changed area, the process involves the skin, bone, muscle and adipose tissue, lymphatic and blood vessels, which causes deformation, an increase in the length and volume of a limb or part of the head, and vascular changes. Since the defective gene is a tumor suppressor, the presence of a mutation sharply increases the likelihood of tumors.
Symptoms
At birth there are no signs of the disease. Pathological manifestations occur in early childhood. The clinical picture is polymorphic. Characteristic symptoms are abnormal enlargement of one or more limbs, macrocephaly, vascular abnormalities (malformations, varicose veins). Some patients exhibit ophthalmological disorders: exophthalmos, strabismus, myopia. With pathological growth of the lower jaw, progeny is formed. Possible skin growth in the area of the soles. Among the possible variants of pathology, the literature mentions isolated enlargement of the spleen or fingers, optic nerve atrophy and retinal pigmentary degeneration in combination with multiple meningiomas.
Enlargement of the lower extremities entails impairment of support and movement. Patients are forced to use orthopedic shoes and special devices (cane, crutches, wheelchair). With enlargement of the upper limbs, difficulties are observed in the process of self-care. Due to deformation of parts of the head, gross cosmetic defects occur, and difficulties in breathing and eating may occur. There is a high probability of developing neoplasms of various localization and histological structure: hamartomas, lipomas, lymphangiomas, hemangiomas, salivary gland adenomas, meningiomas and others.
Complications
A typical symptom of Proteus disease is the occurrence of malignant tumors, which significantly reduce the life expectancy of patients. Other life-threatening consequences of the disease are complications of vascular pathologies. There is an increased risk of deep vein thrombosis. Cases of pulmonary embolism have been described. Due to the increase and difference in the length of the lower extremities, the load on the joints and spine increases, and curvature of the spinal column is formed. Secondary arthrosis and osteochondrosis are detected. More than half of the patients have mental retardation, caused by compression of nerve tissue by enlarged bones of the skull. Convulsions and neurological disorders are possible.
Diagnostics
Due to the low prevalence and similarity of Proteus syndrome to some other congenital diseases, making a diagnosis can present significant difficulties. The diagnostic search process involves specialists in the field of oncology, traumatology and orthopedics, vascular surgery, etc. Hemihypertrophy, vascular anomalies and a tendency to form tumors are considered as the main criteria. The examination plan includes:
- Questioning, inspection. The history reveals abnormal growth of a body part in early childhood and repeated operations for tumors. An external examination reveals a disproportionate, asymmetrical enlargement of the limb(s) or head. It is possible to identify subcutaneous lipomas, ophthalmological disorders, and mental retardation.
- Radiography. An accessible instrumental technique that allows you to assess the condition of the bone structures of the affected area of the body, joints, and spine. X-rays visualize enlarged bones of the skull or segments of the limbs, degenerative-dystrophic changes in the joints and spinal column.
- Tomographic methods. CT and MRI of bones, soft tissues, skull and brain are carried out to clarify the severity of disorders, determine the relationship between bone and soft tissue structures, detect neoplasia, vascular anomalies, bone defects in the skull area, causing compression of the respiratory organs, organs of vision and intracerebral structures.
- Vascular studies. Angiography, Dopplerography, duplex scanning are prescribed for suspected vascular malformations, thrombosis, embolism. They make it possible to determine the severity of vascular damage and choose the optimal treatment tactics.
- Lab tests. Since Proteus syndrome is characterized by a high probability of developing thromboembolic complications, all patients need to assess the state of the hemostatic system (coagulogram).
In case of visual impairment, an ophthalmological examination is prescribed; in case of mental retardation, tests are used to determine the level of intelligence and cognitive abilities. For convulsive syndrome, disorders of the central and peripheral nervous system, consultation with a neurologist is indicated. The disease is differentiated from congenital lipomatosis and Klippel-Trenaunay-Weber, Maffucci, Bannayan-Zonnan syndromes, in which tumors, partial hypertrophy and vascular pathology are also detected. Enlargement of large limb segments is difficult to correct surgically. Interventions are usually performed for hypertrophy of the hands, which makes self-care difficult. Amputations, phalangeal resections, and soft tissue excision are possible.
Prognosis and prevention
Proteus syndrome is a disabling disease that negatively affects the life expectancy of patients. According to research, many patients die in childhood or young adulthood. The causes of death are malignant neoplasia, pulmonary embolism, and thrombosis of large vessels. Preventive measures have not been developed due to the congenital nature of the pathology and insufficient knowledge of the etiology of the disease. Patients suffering from this disease need to undergo regular examinations to assess the condition of the blood coagulation system and early detection of tumors.
X1G) JOURNAL OF CLINICAL MEDICINE OF KAZAKHSTAN
Klinikalyn, Zhagdai / Clinical case / Clinical case
DOI: 10.23950/1812-2892-JCMK-00506
Proteus syndrome and pregnancy
Gulnar Murzabekova1, Lyazzat Saidildina1, Farida Tleuberdieva1, Raushan Berdibekova1, Aigerim Nurmanova1.
"Corporate fund "University Medical Center" National Research Center for Maternal and Child health, department of obstetrics and gynecology, Astana, Kazakhstan.
UDC 616.361:617.053
This work is licensed under a Creative Commons Attribution 4.0 International License
J CLIN MED KAZ 2017; 3(45 SUPPL 3):103-105 Corresponding author: Murzabekova Gulnar Sarkytkazievna, Corporate Foundation “University Medical Center” National Scientific Center for Maternity and Childhood, Department of Obstetrics and Gynecology, Turan St. 32, Astana, Kazakhstan. Phone: +77019999934, E-mail: [email protected]
This paper describes a clinical case of patients with Proteus syndrome. Proteus syndrome is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features. The developmental abnormalities associated with this syndrome can lead to unusual look and overgrowth of different parts of the body. The growth is not symmetrical, which means that the parallel parts of the body are not of the corresponding length of the other. The syndrome is caused due to mutations or mosaic changes in a gene known as AKT1. It is believed that such genetic errors occur shortly after conception. The different bodily defects can be noticed and diagnosed during later toddler-hood or early childhood. The accompanying symptoms begin to appear at this age, which is quite late. It is important to realize that each person with Proteus syndrome will have different medical needs that need individualized treatment.
ZHENA'S GIANT PROTEUS SYNDROMES
Murzabekova G.S.1, Saydildina L.L.1, Tleuberdieva F.N.1, Berdybekova R.R.1, Nurmanova A.M.1
]Ana men bala ^ltshch naked ortalygy "University Medical Center" corporate ^ory, obstetrics and gynecology Belimi, Astana, ^azakhstan.
T¥ZHIRYMDAMA
Makalada Tipi protei syndromemen naukastyts ZHYktiligi men bosanu agymynyts klinikalyk zhagdayi sipattalgan. Proteus syndromes - tua paida bolgan ec si-rek kezdesetsh aura. Bul aura CYYekterdits, teri asty may, kan tamyrlardyts, lymphatamyrlarynyts asymmetrical tez esuimen ZYredi. Sindromnyts sebebi embi-onaldy damu kesetsyde AKT1 gezhde HYktelik mutation, spontaneous gene variationsy paida bolada. Aurudyts auyrlshy tkeley embryoldy damuynyts kay kesetsyde gene mutation sonyts paida boluyn baylanysty, birak birinshi symptomdar baldyrgannyts emrnsch birinshi eki zhylda gana kershedk Proteydsch syndromenyts kerinisi ete aluan Tyrli. Medicinanyts MYmkindikterin shekteulilikpen zhene aurudyts kerUsshsch ertektYrli kerinu sebebyen er syrkatta eat individuals ZYredi.
PROTEUS SYNDROME AND PREGNANCY
Murzabekova G.S.1, Saydildina L.L.1, Tleuberdieva F.N.1, Berdibekova R.R.1, Nurmanova A.M.1
Corporate Foundation "University Medical Center" National Scientific Center for Maternity and Childhood, Department of Obstetrics and Gynecology, Astana, Kazakhstan.
The article describes a clinical case of pregnancy and childbirth in a patient with Proteus syndrome. This case demonstrates the possibility of pregnancy in women with a rare congenital disease and successful delivery. A rare congenital disease, the main features of which are atypical and rapid disproportionate growth of bone and skin, muscles, adipose tissue, blood and lymphatic vessels. As a rule, the disease is accompanied by tumors of individual parts of the body.
Introduction
Proteus syndrome is an extremely rare congenital disease, the main features of which are atypical and rapid disproportionate growth of bone and skin, muscles, adipose tissue, blood and lymphatic vessels. As a rule, the disease is accompanied by tumors of individual parts of the body.
The first descriptions of this syndrome were made in 1979 by Michael Cohen. Proteus syndrome
has multiple clinical manifestations and therefore presents difficulties in diagnosis and further treatment.
The syndrome is caused by spontaneous variation of a gene during embryonic development. A point mutation occurs in the AKT1 gene. AKT1 mutations modify the activity of the cellular AKT protein, which activates sporadic tissue growth. In patients with Proteus syndrome, increased activity of the AKT protein was found,
In healthy people, this protein is inactive. This mutation in the LKT1 gene impairs the ability of affected cells to regulate their own growth, causing some parts of the patient's body to grow to abnormal sizes while others remain normal. The severity of the disease directly depends on the period of embryonic development, when the genetic mutation itself occurred, leading to at least the formation of three subtypes of cells - normal, atrophic and hypertrophic, but the first symptoms appear only in the first two years of the baby’s life. This partial genetic mutation of the LKT1 gene is not detected in blood tests. It is important to collect tissue samples, including bone, cartilage, and growth plates, when patients undergo surgery.
There are no obvious signs of the disease at birth. Signs of Proteus syndrome are detected in the first 2 years of a child’s life. At birth, there are usually no obvious signs of disease. With age, it can lead to excessively rapid growth of tumors. Average life expectancy is reduced in those affected, often from an increased incidence of deep vein thrombosis and pulmonary embolism, which can receive complications from diseases associated with vascular malformations. Due to the increase in weight of the deformed limb, muscle and joint pain may appear. The disease itself does not cause mental retardation. Tissue proliferation can lead to secondary damage to the nervous system, which in turn leads to cognitive impairment. Sufferers are at increased risk of developing certain types of cancer, tumors, meningiomas and salivary gland adenomas. In addition to the growth of the limbs, thickening of the soles of the feet and various skin lesions occur. There are also patients who have developed neurological complications such as seizures, mental retardation and vision loss. It should be taken into account when making a diagnosis that tissue proliferation in Proteus syndrome is asymmetrical.
Diagnosis of Proteus syndrome, the earlier the disease itself is identified, the more the chances of a comfortable future life increase. It is impossible to get rid of the syndrome, just like any other congenital or hereditary disease.
Until today, clinical diagnosis consists of:
Regular monitoring of the patient to prevent the development of complications of concomitant diseases.
Consultation with a geneticist; for an accurate genetic diagnosis, a tissue biopsy is necessary, because the failure that causes mutations in LCT1 is often also present in white blood cells selected for genome analysis.
Proteus syndrome is difficult to treat, as it manifests itself differently in each patient. Treatment of pathological symptoms in combination with the correction of complex disorders of the bones and spine, as well as monitoring of children, improving medical knowledge and experience - all in order to find a cure for the successful treatment of a rare disease.
Clinical manifestations and symptoms:
Manifestations of Proteus syndrome are very diverse. The main ones are:
Excessive growth of any part of the body, e.g.
face, limb, body, finger, neck. This violation is always asymmetrical, that is, it is more pronounced on the right or left than on the other side.
Various skin formations, including: flaming nevus, epidermal nevus, which can be sebaceous or warty, angiokeratoma.
Congenital tumors: hemangiomas, lymphangiomas, lipomas.
Violation of normal skin coloring: hyperpigmentation (excessive coloring) or hypopigmentation (lack of coloring).
Finger defects, among which syndactyly is most common.
Malformations of the skull, spine (scoliosis) and internal organs
Hypertrophy of the skin of the soles.
Macroglossia and hemifacial macrosomia.
tumors and adenomas of the sclera, salivary glands,
subcutaneous tumors.
Pulmonary embolism, deep vein thrombosis.
Treatment is determined for each patient
individually, due to the limited capabilities of medicine and the heterogeneity of the manifestation of the disease.
Treatment of Proteus syndrome involves:
Detection of deviations from the norm at an early stage;
Application of symptomatic and preventive treatment.
Hemihyperplasia:
Corrected by an experienced orthopedist, since different leg lengths can cause complications;
Enlarged fingers create a lot of problems for the patient in everyday life: when writing, when grasping movements, etc.
Macroglossia and hemifacial macrosomia:
May affect the formation of malocclusion;
Observation by an orthodontist is necessary; maxillofacial surgery is indicated.
Early and correct diagnosis prevents the progression of symptoms and the development of complications.
Skin and subcutaneous abnormalities:
They need regular monitoring, since vascular anomalies and lipomas can lead, in addition to local ones, to systemic disorders.
Skin vascular spots and abnormalities:
Laser treatment may be used to eliminate skin vascular spots and possible other abnormalities.
For acute pain in the arms and legs, difficulty breathing, and constant shortness of breath, complex treatment is prescribed.
Internal damage:
Internal damage (pulmonary cysts, lipomas) will help identify magnetic resonance imaging of the abdominal cavity and chest.
In the standard treatment of Proteus syndrome, drug treatment does not play a significant role.
Surgical treatment: Orthopedic intervention is possible for progressive scoliosis. Sometimes, in order to be able to use their hands and wear shoes normally, patients need surgery
to shorten fingers that are too long. When performing facial surgery, a preliminary consultation with a plastic surgeon is necessary. All subcutaneous lesions that occur on vital organs require immediate intervention. Internal lung cysts and lipomas will require surgery.
Scientists around the world are working to create a drug that would block the supra-dimensional activity of the protein in the earliest stages of the disease.
Case description
Our observation presents a case of the development of pregnancy in a patient with Proteus syndrome, who was registered for pregnancy at the National Scientific Center for Maternity and Childhood in the Department of Women's Health and Management of Pregnant Women with a diagnosis of Pregnancy 10 weeks 3 days. Proteus syndrome. Mild myopia. Secondary lymphostasis, hemangiomatosis of the left upper and lower extremities. Residual encephalopathy. Oblique pelvis.
When receiving complaints, he does not make active complaints.
From the anamnesis: a pregnant woman has a congenital pathology, Proteus syndrome (unilateral hypertrophy combined with changes in skin coloration). In childhood (1995), a comprehensive examination was carried out in Germany: a hereditary syndrome was excluded (arises as a result of a somatic mutation at an early embryonic level). A 3 cm shortening of the leg length on the right side was detected, and it was recommended to wear orthopedic shoes. The bone structure of the hip joint and left leg is normal, in the pelvic area there is a displacement to the right side. The left arm is longer than the right.
Repeated examination in Germany in 2004: pronounced hemihypertrophy with pronounced asymmetry of half the face, hemangiomatous skin changes in the upper part of the left arm, in the upper part of the right thigh and in the area of the left chest and right side. The pelvis is 2 cm crooked to the right. An examination of the internal organs, lymph nodes, and skin did not reveal any abnormalities in the structure of the internal organs, and no increase in hemangiomas or subcutaneous neoplasms was detected.
There is also myopia -1.5 D.
Menstrual function without any peculiarities, sexual activity since 18 years. This is the first pregnancy. Last menstruation April 19, 2015.
A complete clinical and laboratory examination was carried out in the Women's Health Department. The patient was examined by specialists: a vascular surgeon, a geneticist, and a neurologist.
Conclusion of the vascular surgeon: there is secondary lymphostasis, hemangiomatosis of the left upper and lower limbs against the background of congenital Naevi syndrome. At the time of examination there were no contraindications to pregnancy. It is recommended to wear elastic stockings and sleeves, Detralex 1 tablet 2 times a day until delivery.
Geneticist's conclusion: there are no contraindications to pregnancy. A repeat examination with the results of ultrasound examinations of the first and second trimesters is recommended.
Neurologist's conclusion: Residual encephalopathy, there are no contraindications to carrying the pregnancy to term, it is recommended to exclude the period of pushing during childbirth.
General condition is satisfactory.
Physique features - the left half of the body is hypertrophied: thickening of the left cheek, left arm, left leg (OG left bottom - 24.5 cm, OG bottom right 20 cm, OG left top 36 cm, OG right top 30 cm, OB left bottom 42 cm, OB right bottom 33 cm, OB left top 54 cm, OB right top 48 cm). Moderate nutrition.
The skin is of normal color; there are extensive hemangiomas - nevus - on the left upper limb, left mammary gland, right half of the torso and right lower limb.
Blood pressure 100/50, 100/60 mmHg, pulse 80 beats per minute. The mammary glands are soft,
painless. The tongue is moist, slightly coated. The abdomen is soft and painless. The symptom of effleurage is negative. Stool and diuresis are not disturbed.
An emergency surgical delivery occurred in the hospital at 38 weeks' gestation. A girl was born, full-term, diva, with a body weight of 2760.0 g, body length 51 cm, with an Apgar score of 7-9 points. The early neonatal period proceeded without complications. During childbirth, blood loss was 600.0 ml. The postpartum postoperative period was uneventful. Discharged in satisfactory condition on the 4th day of the postoperative period with the child.
Discussion
Proteus syndrome is a random genetic mutation, so it is impossible to prevent its development. The cause of the disease is mosaicism of somatic cells containing a dominant gene that has not yet been identified. However, due to the fact that symptoms appear immediately, the hypothesis of postzygotic embryonic recombination has been put forward, which leads to the emergence of three types of cells - normal, hypertrophic, atrophic. SP is almost always characterized by excessive asymmetric tissue growth, which often begins after 6-18 months of life, and rapid progression.
The prognosis is favorable in most cases. A more serious prognosis with the development of organ complications. In this case, the pregnant patient underwent preventive measures aimed at preventing bleeding. After birth, it is recommended to consult a geneticist for the child.
Literature:
1. Boris N.W., Damna J.H., Owens J.A. Proteus syndrome. 2010; 6(9):36-38.
2. Solonichenko V.G., Shafranov V.V., Kucherov Yu.I., Zhirkova Yu.V., Burov A.A. Sindrom proteya u novorozhdennogo. Pediatric surgery 2007; 4(5):48-50.
Proteus syndrome is a genetic disease that is congenital. In this case, the person not only becomes disabled, but also undergoes rapid and pronounced extensive deformation.
At the same time, other diseases develop that can significantly shorten the patient’s life.
What is Proteus syndrome
The name of this disease comes from the Greek myth about the sea god who could change the shape of the body. The disease has similar symptoms and clinical picture.
In fact, this is a congenital condition in which skin and bone tissue grow rapidly. the condition is often accompanied by tumors of entire parts of the body.
Michael Cohen first asked the question of this pathology back in 1979. Already at that time, he discovered about 200 cases of the development of the condition in people with genetic disorders of this type around the world.
Later studies showed that about half of the cases belong to other diseases with similar symptoms. As a result, medical research has shown that the disease is rarer.
Important! Sometimes more weakened types of Proteus syndrome are recorded, and therefore often patients simply do not seek help.
Proteus syndrome provokes the growth of skin, muscles, bones, adipose tissue, lymphatic and blood vessels. Immediately after birth, in the vast majority of cases, patients have no external signs.
As the child develops, tissues begin to actively grow, causing atypical tissue hypertrophy. Ultimately, this can lead to the development of tumors.
In addition to such conditions, the average life expectancy of patients with Proteus syndrome is often reduced due to the development of pulmonary embolism and deep vein thrombosis. Such complications occur due to vascular malformation.
Due to the increase in weight of the affected parts of the body and limbs in particular, joint and muscle pain begins to develop. This manifests itself under the influence of the altered shape of tissues, which can become pinched, experience intense and uneven load, which significantly loads the nervous system.
In fact, the disease itself is not a provoking factor for the manifestation of mental retardation, but it is important to take into account the factor of tissue proliferation. Nerve endings and the peripheral nervous system are often affected by this process. This is what can lead the patient to cognitive impairment.
Patients with Proteus syndrome have an increased risk of developing malignancies. The most common types of cancer found in such situations are meningiomas, salivary gland adenomas, and other types of cancer. The manifestation of benign tumors is inevitable.
Important! Complications can also develop due to excessive tissue growth, which is what happened in one of the most famous cases with Joseph Merrick. He suffocated in his sleep due to the fact that the cervical region could not withstand the load and bent under the weight of his head.
Causes
The causes of this condition are genetic and chromosomal disorders that occur during intrauterine development of the fetus. That is, pathology is often an accidental manifestation, although some scientists also support the hereditary form of transmission as the main risk factor.
Statistics have shown that symptoms may differ from case to case. Sometimes the manifestations of pathology are so insignificant that patients often prefer not to see a doctor. But most often clinical manifestations have the following characteristics:
- Significant growth of tissues of all types;
- Joint and muscle pain;
- Limited mobility;
- Poor blood circulation and innervation;
- Decreased reflexes.
The rest of the symptoms may be supplemented depending on which part was affected to the greatest extent. If in the neck area, then this is a circulatory disorder, leading to dizziness, shortness of breath, and so on. if in the head area, the nervous system and the corresponding functions of the body are significantly affected - from speech and coordination to the sensitivity of the skin, the work of the heart and blood vessels, ophthalmological and auditory disorders, and so on.
Also in the clinical picture, the development of other diseases plays an important role - tumors, vascular malformation, thromboembolism, and so on.
Diagnostics must be carried out in order to identify a child with such disorders. Ultrasound is mandatory during pregnancy.
If there is a suspicion that the condition is present in a child, then an examination must be carried out by an orthopedist, oncologist, vascular surgeon and other specialists. The selected methods are:
- Survey and inspection;
- X-ray;
- Angiography;
- Dopplerography;
- Duplex scanning;
- Coagulogram and other laboratory tests.
If there are disturbances in a particular organ system, the patient is referred to the appropriate specialists to carry out the necessary tests. It is also necessary to differentiate from diseases such as Maffucci, Klippel-Trenore-Weber, Bannayan-Zonnan syndromes, lipomatosis, and so on.
Therapy is carried out depending on the manifestation of specific disorders. All efforts are aimed at prolonging the patient's life. Considering that the disease is genetic in nature, medications in this case are often ineffective.
But at the same time, medications can help eliminate the symptoms of the disease, such as pain, thrombosis and other similar conditions. That is why the presented type of treatment requires careful diagnosis.
If we talk about other treatment methods, the disease can be corrected surgically, but not completely cured. Tissue growth will still continue. Corrective manipulations can be plastic or to improve the functionality of the affected area.
If complications develop, tumor removal and vascular interventions may be required. In some cases, amputation of non-viable tissue is performed.
Forecast
The prognosis for Proteus syndrome is unfavorable. The disease is disabling and can significantly shorten the patient's life expectancy. As studies show, most patients die at a young age or even in childhood. The causes of death are either malignant tumors or blood clots.
What is Proteus syndrome, watch in our video:
