What is it?
Proteus syndrome is a rare disease characterized by significant growth of bones, skin and other tissues. The organs and tissues affected by this pathology are disproportionately large in relation to the rest of the body.
This abnormal size of certain organs and / or tissues is generally asymmetrical. Indeed, the disease can affect the left side as well as the right side of the body in a different way.
Newborns with Proteus syndrome have very few, if any, characteristic signs of the disease.
The disease usually develops between 6 and 18 months and intensifies with age.
The disease can affect different parts of the body. The long and short bones, the skull and the spine are most often affected.
It can also be the cause of tumor tissue development in the skin.
Blood vessels and adipose tissue may also be affected by abnormal size.
In some cases, Proteus syndrome can cause neurological deficiencies as well as intellectual difficulties, contractions and loss of vision. Affected individuals may also have defects in facial development, such as an elongated face, defects in the ends of the eyes, a “low bridge” nose, an open mouth expression, etc.
for some unknown reasons, people with the disease and neurological symptoms are more likely to develop these types of facial defects.
Other potential complications are also visible in the context of Proteus syndrome. This is particularly the case of an increased risk of developing benign tumors. Or blood clots (deep vein thrombosis development, mainly in the deep veins of the arms and legs). These clots may then pass into the bloodstream and then lodge in the lungs and cause complications: pulmonnaire risk of embolism.
Pulmonary embolism is the leading cause of death in patients with this condition.
Proteus syndrome is a rare disease whose incidence does not exceed 1 in 1,000,000.
Symptoms of Proteus Syndrome
The symptoms associated with Proteus syndrome are:
megalodactyly: hypertrophy (increased volume of a tissue or organ) of the fingers and toes;
– vertebral abnormalities;
– asymmetrical development of limbs;
– hyperostosis: excessive production of bone tissue;
– excessive growth of viscera (spleen, thymus, etc.);
– uneven distribution of adipose tissue (fat);
– asymmetrical muscle development;
– connective tissue naevi: cutaneous abnormalities in the development of cells containing melanin.
Calcification of the connective tissue (accumulation of calcium deposits in the tissue whose main function is the maintenance and protection of other body tissues) as well as long bone lengthening are also observable in cases of Portée Syndrome.
Subjects with this syndrome are more likely to develop bilateral ovarian cystadenomas (ovarian cysts) or parotid monomorphic adenomas (salivary tumors).
Blood clots can also occur in the tissues and then pass through the blood vessels. These clots can reach the lungs and cause pulmonary embolism. The incidence of these thromboembolic consequences is high.
The origins of the disease
Proteus syndrome is a genetic disease; it is the consequence of a mutation in the AKT1 gene. This disease is however not hereditary because it is not transmitted to the offspring.
The mutation in this gene of interest occurs randomly at the level of a cell in the early stages of fetal development. In the development of the subject, cells continue to divide. Some of them will have the mutation, and some will not. This cell group composed of mutated and unmutated cells forms a genetic mosaic.
This AKT1 gene comes into play in the regulation of cell growth, in cell proliferation as well as in cell death. A mutation in this gene therefore causes a disruption in the ability of cells to self-regulate. This results in uncontrolled cell proliferation in different tissues and organs leading to abnormal magnification of certain limbs and / or organs.
The mutations within this AKT1 gene are the most characteristic in the development of the disease.
Other hypotheses regarding the correlation between the presence of mutations in the PTEN gene and the development of Proteus syndrome have been reported. These hypotheses are the subject of controversy among scientists.
Indeed, the PTEN gene produces the enzyme (particular protein) phosphatidylinositol 3-kinase (PI3K). This protein is a signaling pathway for the AKT gene. In this sense, mutations in the PTEN gene can lead to a signaling defect for the AKT gene. These mutations therefore have indirect consequences in the role of the AKT gene.
Risk factors for Proteus Syndrome
Since Proteus syndrome is not a hereditary disease, the risk factor for the transmission of the disease to the offspring does not exist here, or very little.
The mutation concerning the AKT1 gene is a non-hereditary somatic mutation.
Nevertheless, mutations in the PTEN gene can be transmitted to offspring through autosomal dominant inheritance. That is, the presence of a single copy of the mutated allele for the gene within a non-sexual chromosome is sufficient for the subject to develop the phenotype associated with the disease. In addition, this risk factor for inherited transmission for this gene involved in the development of the disease is a low risk factor.
Prevention and treatment of Proteus Syndrome
Treatment for the disease is interventions to control abnormal bone growth. These interventions are:
– The epiphysiodère: total or partial cartilage fusion to stop the growth of bone tissue;
– amputation, in extreme cases.
Physiotherapy and the mobilization of a group of health professionals are important in the supervision of the patient:
– the use of orthosis or custom-made shoes may be necessary;
– dermatological treatment;
– Surgical more or less important can also be treated for deformities and a reduction of pain.
Monitoring the subject with Proteus syndrome is very important. In particular through a close monitoring of the development of tumors. Regular physiotherapeutic and radiological examinations are often recommended.
In addition, psychological counseling is often associated and beneficial for the patient and his family.
The prognosis is dependent on the severity of the disease.