Proteus syndrome is a rare genetic condition characterized by the disproportionate and often asymmetrical growth of various tissues throughout the body. This condition is extremely rare, affecting fewer than 1 in 1,000,000 live births, with approximately 200 cases reported worldwide. The name “Proteus” originates from the ancient Greek god of change, reflecting the unpredictable and variable nature of the syndrome’s manifestations.
Defining Proteus Syndrome
Proteus syndrome is a sporadic and progressive disorder marked by the overgrowth of various tissues. This overgrowth affects different parts of the body unevenly and can progress over time. Newborns with Proteus syndrome usually show no signs of the condition, with atypical growth beginning to appear between 6 and 18 months of age and often becoming more severe through the first decade of life.
The Genetic Origin
Proteus syndrome is caused by a somatic mutation in the AKT1 gene. This mutation occurs after conception, meaning it is not inherited from parents. The AKT1 gene plays a role in controlling cell growth and division, and the mutation disrupts this regulation, leading to abnormal cell proliferation. This results in mosaicism, a condition where some cells in the body carry the mutation while others do not. The patchy, asymmetric overgrowth observed in individuals with Proteus syndrome is a direct consequence of this mosaic distribution of mutated cells.
Key Clinical Manifestations
The clinical presentation of Proteus syndrome is highly variable, with overgrowth affecting skin, bone, fatty tissue, and blood vessels. This can impact almost any part of the body, including limbs, the skull, and internal organs. Individuals may experience skeletal overgrowth leading to differences in limb length, spinal curvature (scoliosis), and bone deformities. A distinctive skin lesion called cerebriform connective tissue nevus, characterized by thick, raised, and deeply grooved skin, often forms on the soles of the feet but can also appear on the hands.
Beyond overgrowth, other features include vascular malformations, such as abnormal capillaries and veins, and the development of mostly benign tumors like lipomas. Individuals also have an increased risk for certain benign tumors. Some people with Proteus syndrome also experience neurological abnormalities, including intellectual disabilities, seizures, and vision loss. Distinctive facial features, such as a long face, downward-slanting eyes, a flat nasal bridge with wide nostrils, and an open-mouth expression, may also be present.
Management Approaches
There is currently no cure for Proteus syndrome, so management focuses on addressing specific symptoms and complications as they arise. A multidisciplinary team of specialists is typically involved in care, which may include orthopedic surgeons for bone issues, dermatologists for skin concerns, neurologists for neurological symptoms, and hematologists to monitor for blood clots. Surgical interventions are often necessary to manage overgrowth, correct skeletal deformities, or remove problematic tissues.
Physical therapy and occupational therapy are important to improve movement and mobility, and custom orthotics or footwear may be required. Monitoring for the development of deep vein thrombosis (DVT) is important, as these blood clots, particularly in the legs or arms, can lead to life-threatening pulmonary embolisms if they travel to the lungs. Regular surveillance for potential tumor development is also part of ongoing care.
Prognosis and Support
The long-term outlook for individuals with Proteus syndrome varies significantly, depending on the severity and location of the overgrowth and associated complications. While some complications can be life-threatening, particularly deep vein thrombosis and pulmonary embolism, which are leading causes of death, many individuals can lead fulfilling lives with appropriate medical care. Approximately 25% of individuals with Proteus syndrome may die before the age of 22, often due to pulmonary embolisms. Those with milder symptoms tend to have a more favorable prognosis with effective treatment. Psychosocial support is beneficial for individuals and their families, helping them navigate the challenges associated with the syndrome’s visible manifestations and potential complications.