Proteus syndrome is a rare complex disorder, characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease overgrows asymmetrically; the disease may affect the right and left sides differently and also can affect any part of the body. With only a few hundred cases reported, it has an incidence of less than 1 in 1 million people worldwide; males are almost twice more likely to be affected compared to females. Overgrowth starts between the ages of 6 and 18 months and gets more severe with time.
Proteus syndrome is characterized by macrodactyly, vertebral abnormalities, and asymmetric limb overgrowth and length discrepancy. Hyperostosis, overgrowth of viscera (spleen, thymus), abnormal and disproportionate fat distribution, asymmetric muscle development, connective-tissue nevi, epidermal nevi, and vascular malformations may also be seen. Proteus syndrome is also characterized by thrombo embolic manifestations, pulmonary cystic malformations, calcified connective tissue, and elongation of long bones with abnormal thinning. Some patients affected with Proteus syndrome have neurological abnormalities, including intellectual disability, seizures, and vision loss. Some may also have distinctive facial features such as a long face, outside corners of the eyes that point downward (down-slanting palpebral fissures), a low nasal bridge with wide nostrils, and an open-mouth expression.
Proteus syndrome is caused by a mutation in the AKT1 gene. AKT1 regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis. A mutation in this gene disrupts a cell's ability to regulate its own growth; it will grow and divide abnormally. The AKT1 gene is an autosomal dominant lethal gene, mutation in this gene is not inherited from a parent; it arises randomly in one cell during the early stages of development before birth. As cells continue to grow and divide, some cells will have the mutation and other cells will not, resulting in a mosaic state.