Proteus syndrome is a rare congenital pathology manifested by abnormal growth of individual parts of the body. Usually, an increase in the area of the head, arm or leg is detected. Partial hypertrophy is combined with an increased likelihood of thrombosis and thromboembolism, the formation of tumors of various structures and localization. The diagnosis is made based on the results of the examination, radiography, CT, MRI, angiography, Dopplerography. Radical treatment has not been developed. Orthopedic devices are used, according to indications, operations are performed to improve the functions of the limb, facilitate breathing and eating, surgical removal of neoplasms is performed.
ICD 10
Q87.5 Other syndromes of congenital anomalies with other skeletal changes
Meaning
Proteus syndrome (partial gigantism) is a very rare congenital disease. About 200 cases of this pathology are mentioned in the literature, while experts do not exclude that some patients may have suffered 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, 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 probability of developing tumors and a tendency to thrombosis.
Causes
The cause of the disease is somatic mosaicism, presumably caused by a random mutation of the dominant gene. Some experts question the random nature of the mutation, relying on information about the identification of several cases of mild signs of the syndrome in the parents of patients. There are studies according to which the pathology is caused by a mutation of the PTEN gene located at the 10q X chromosome locus. At the same time, the researchers point out that mutations of this gene are found in only 20% of patients with Proteus syndrome and are determined in some other diseases characterized by an increased likelihood 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 altered area, the skin, bone, muscle and adipose tissue, lymphatic and blood vessels are involved in the process, which causes deformation, an increase in the length and volume of the limb or part of the head, vascular changes. Since the defective gene is a tumor suppressor, the presence of a mutation dramatically increases the likelihood of neoplasms.
Symptoms
There are no signs of the disease at birth. Pathological manifestations occur in early childhood. The clinical picture is polymorphic. Characteristic symptoms are abnormal enlargement of one or more limbs, macrocephaly, vascular anomalies (malformations, varicose veins). In some patients, ophthalmological disorders are detected: exophthalmos, strabismus, myopia. With pathological growth of the lower jaw, progenia is formed. There may be an overgrowth of the skin in the area of the soles. Among the possible variants of pathology, literature sources mention isolated enlargement of the spleen or fingers, optic nerve atrophy and retinal pigmented degeneration in combination with multiple meningiomas.
An increase in the lower extremities entails a violation of support and movement. Patients are forced to use orthopedic shoes and special devices (cane, crutches, wheelchair). With an increase in the upper limbs, difficulties are observed in the self-service process. Due to the deformation of parts of the head, gross cosmetic defects occur, difficulties with breathing and eating may be noted. 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 sign of Proteus disease is the occurrence of malignant tumors that significantly shorten the life expectancy of patients. Other life-threatening consequences of the disease are considered 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 limbs, the load on the joints and spine increases, a curvature of the spinal column is formed. Secondary arthrosis, osteochondrosis are detected. More than half of the patients have mental retardation due to compression of nerve tissues by enlarged bones of the skull. Seizures, neurological disorders are possible.
Diagnostics
Due to the low prevalence, similarity of Proteus syndrome with some other congenital diseases, diagnosis can present significant difficulties. Specialists in the field of oncology, traumatology and orthopedics, vascular surgery, etc. take part in the process of diagnostic search. hemihypertrophy, vascular abnormalities and a tendency to tumor formation are considered as the main criteria. The survey plan includes:
- Survey, inspection. In the anamnesis, abnormal growth of a part of the body in early childhood, repeated operations for neoplasms are determined. An external examination reveals a disproportionate asymmetrical enlargement of the limb (limbs) or head. It is possible to detect subcutaneous lipomas, ophthalmic disorders, 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, spine. Enlarged bones of the skull or limb segments, degenerative-dystrophic changes of joints and vertebral column are visualized on radiographs.
- Tomographic methods. CT and MRI of bones, soft tissues, skull and brain are carried out to clarify the severity of disorders, to determine the relationship between bone and soft tissue structures, to detect neoplasms, vascular anomalies, bone defects in the skull that cause compression of the respiratory organs, the organ of vision and intracerebral structures.
- Vascular studies. Angiography, dopplerography, duplex scanning are prescribed if vascular malformations, thrombosis, embolism are suspected. They make it possible to determine the severity of vascular damage, choose the optimal treatment tactics.
- Laboratory tests. Since Proteus cider is characterized by a high probability of thromboembolic complications, all patients need to assess the state of the hemostasis system (coagulogram).
In case of violations on the part of the organ of vision, an ophthalmological examination is prescribed, in case of mental retardation, tests are used to determine the level of intelligence, cognitive abilities. In case of convulsive syndrome, disorders of the central and peripheral nervous system, a neurologist’s consultation is indicated. The disease is differentiated with congenital lipomatosis and Klippel-Trenone-Weber, Maffuchi, Bannayan-Sonnan syndromes, in which tumors, partial hypertrophy and vascular pathology are also detected.
Treatment
Pathogenetic therapy has not been developed, treatment is only symptomatic. According to the indications, orthopedic correction is carried out using special shoes, orthoses, corsets with secondary changes in the spine. Prescribe medication therapy for the prevention of thrombosis. Due to the involvement of various organs and systems, surgical treatment measures are carried out by various specialists, including orthopedists, oncologists, neurosurgeons, vertebrologists, vascular surgeons, cosmetic surgeons, maxillofacial surgeons, etc. The following groups of operations for Proteus syndrome can be distinguished:
- In case of pathology of the extremities. Enlargement of large limb segments is difficult to correct surgically. Interventions are usually performed with hypertrophy of the hands, which makes self-care difficult. Amputations, resections of the phalanges, excision of soft tissues are possible.
- With changes in the facial skeleton. In case of respiratory disorders, enlarged areas of bones and soft tissue structures are removed to restore the lumen of the respiratory tract. In case of malocclusion, according to indications, resections of the upper or lower jaw are performed, orthodontic devices are applied. In case of gross cosmetic defects, plastic reconstruction is carried out.
- With vascular anomalies. With the development of complications, thromboembolectomy, ligation of an artery or vein, and other vascular interventions may be required.
- With neoplasms. Surgical tactics are determined by the size and degree of neoplasia malignancy. Benign tumors are removed using traditional techniques or modern technologies (electrocoagulation, laser exposure, radiosurgery), with malignant lesions, extended operations are performed.
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 at a young age. The causes of death are malignant neoplasia, PE, thrombosis of large vessels. Preventive measures have not been developed due to the innate nature of the pathology and insufficient knowledge of the etiology of the disease. Patients suffering from this disease should be regularly examined to assess the state of the blood coagulation system, early detection of neoplasms.
Literature
- Proteus syndrome. A case report of a hamartomatous syndrome with severe mandibular hemihypertrophy. Pinto PX, Beale V, Paterson AW. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Jan;85(1):82-5. link
- Pathology of lipomatous lesions in Proteus syndrome. Tihan T, Okun J. Pediatr Dev Pathol. 1998 Sep-Oct;1(5):443-8. link
- An unusual initial presentation of Proteus syndrome: macrosyndactyly. Türk CY, Güney A, Oner M, Halıcı M. Eklem Hastalik Cerrahisi. 2011;22(1):56-9. link
- Proteus syndrome: diagnosis and surgical management. Vaughn RY, Selinger AD, Howell CG, Parrish RA, Edgerton MT. J Pediatr Surg. 1993 Jan;28(1):5-10. link