About encephalocraniocutaneous lipomatosis

What is encephalocraniocutaneous lipomatosis?

Proteus syndrome is a rare disorder characterized by overgrowth of various tissues of the body. The cause of the disorder is a mosaic mutation in a gene called AKT1. Disproportionate, asymmetric overgrowth occurs in a mosaic pattern (i.e., a random "patchy" pattern of affected and unaffected areas). Affected individuals may experience a wide variety of complications that may include progressive skeletal malformations, benign and malignant tumors, malformations of blood vessels (vascular malformations), bullous pulmonary disease, and certain skin lesions. In some cases, life-threatening conditions relating to abnormal blood clotting may develop including deep vein thrombosis and pulmonary embolism.

What are the causes for encephalocraniocutaneous lipomatosis?

ECCL can result from mutations in the FGFR1 gene, which provides instructions for making a protein called fibroblast growth factor receptor 1 (FGFR1). This receptor interacts with proteins called fibroblast growth factors (FGFs) to trigger signaling within cells. Signaling via the FGFR1 protein is involved in many critical processes, such as cell division and the regulation of cell growth and maturation. This signaling is important for the normal development and growth of several parts of the body, including the brain.

The FGFR1 gene mutations that cause ECCL arise 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 others will not. This mixture of cells with and without a genetic mutation is known as mosaicism. In cells with an altered FGFR1 gene, the resulting FGFR1 protein is overactive, triggering abnormal signaling that affects cell growth and division. Researchers are studying how these changes in signaling lead to the growth of noncancerous tumors and the other features of ECCL.

In some people with ECCL, no FGFR1 gene mutation has been identified, and the cause of the disease is unknown. Other genetic changes are under study as possible causes of this condition.

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