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 of a disproportionate size compared to the rest of the body.

This abnormal size of certain organs and / or tissues is generally asymmetrical. This is because the disease can affect the left side as well as the right side of the body in different ways.

Newborns with Proteus syndrome show very few, if any, characteristic signs of the disease.

The disease usually develops between 6 and 18 months and intensifies with age. (1)

The disease can affect different parts of the body. Long and short bones, skull and spine are most often affected.

It can also be the cause of the development of tumor tissue in the skin.

Blood vessels as well as fatty tissue can also be affected by abnormal lumps. (1)

In some cases, Protée syndrome can lead to neurological impairments as well as intellectual difficulties, contractions and loss of vision. People with the disease may also have defects in facial development, such as an elongated face, defects in the ends of the eyes, a “low” nose, an open mouth expression, and so on.

For some as yet unknown reasons, people affected by the disease and exhibiting neurological symptoms are more likely to develop these types of facial defects. (1)

Other potential complications are also visible in Proteus syndrome. This is particularly the case with an increased risk of developing benign tumors. or blood clots (development of deep vein thrombosis, mainly in the deep veins of the arms and legs). These clots may then pass into the blood vessels and then lodge in the lungs and thus cause complications: risk of pulmonary embolism.

Pulmonary embolism is the major cause of death in patients with this pathology. (1)

Proteus syndrome is a rare disease with an incidence of no more than 1 in 1.

Symptoms associated with Proteus syndrome are: (2)

– megalodactyly: hypertrophies (increase in the volume of a tissue or organ) of the fingers and toes;

– vertebral anomalies;

– asymmetric development of the limbs;

– hyperostosis: excessive production of bone tissue;

– excessive growth of the viscera (spleen, thymus, etc.);

– uneven distribution of adipose tissue (fat);

– asymmetric muscle development;

– connective tissue nevi: skin abnormalities in the development of cells containing melanin.

– vascular deformations.

Connective tissue calcification (accumulation of lime deposits in the tissue whose main function is the maintenance and protection of other body tissues) as well as an elongation of long bones are also observable in cases of Portée syndrome. (2)

People with this syndrome are more likely to develop bilateral ovarian cystadenomas (cysts in the ovaries) or even monomorphic parotid adenomas (salivary tumors).

Blood clots can also occur in tissues and then pass through blood vessels. These clots can then reach the lungs and cause pulmonary embolism. The incidence of these thromboembolic consequences is high.

Protée syndrome is a genetic disease, it is the consequence of a mutation in the AKT1 gene. However, this disease is not hereditary because it is not transmitted to the offspring.

The mutation in this gene of interest takes place randomly in a cell present in the early stages of fetal development. As part of the subject’s development, the cells therefore continue to divide. Some of them will have the mutation, and some will not. This cell group made up of mutated and non-mutated cells forms a genetic mosaic.

This AKT1 gene is involved in the regulation of cell growth, cell proliferation and cell death. A mutation in this gene therefore causes a deregulation in the capacity of cells to self-regulate. This leads to uncontrolled cell proliferation in different tissues and organs leading to abnormal enlargement of certain limbs and / or organs.

Mutations within this AKT1 gene are the most characteristic in the development of the disease. (1)

Other hypotheses as to the correlation between the presence of mutations in the PTEN gene and the development of Protée syndrome have been put forward. These assumptions are the subject of controversy among scientists.

Indeed, the PTEN gene produces the enzyme (specific 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. (3)

As Protée syndrome is not an inherited disease, the risk factor for the transmission of the disease to the offspring therefore does not exist here, or very little.

The mutation in the AKT1 gene is a non-inherited somatic mutation.

However, mutations in the PTEN gene can be transmitted to offspring through autosomal dominant inheritance. Either, 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. Furthermore, this risk factor for hereditary transmission for this gene entering into the development of the disease is a low risk factor.

Treatment for the disease is interventions to control abnormal growth in the bones. These interventions are:

– the epiphysiodère: total or partial fusion of cartilage making it possible 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: (3)

– the use of orthosis or custom-made shoes may be necessary;

– dermatological treatment;

– more or less important surgical interventions can also be the object of a treatment of the deformities and a reduction of the pains.

Monitoring of the subject with Proteus syndrome is very important. In particular through a close follow-up of the development of tumors. Regular physiotherapeutic and radiological examinations are often recommended.

In addition, psychological monitoring is often associated and beneficial for the patient and his family.

The vital prognosis is dependent on the severity of the disease.