Winchester syndrome is a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. Winchester syndrome used to be considered part of a related condition now called multicentric osteolysis, nodulosis, and arthropathy (MONA). However, because Winchester syndrome and MONA are caused by mutations in different genes, they are now thought to be separate disorders.

Winchester syndrome is caused by mutations in the MMP14 gene (also known as MT1-MMP). This gene provides instructions for making a protein called matrix metallopeptidase 14, which is found on the surface of cells. Matrix metallopeptidase 14 normally helps modify and break down various components of the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. These changes influence many cell activities and functions, including promoting cell growth and stimulating cell movement (migration). Matrix metallopeptidase 14 also turns on (activates) a protein called matrix metallopeptidase 2. The activity of matrix metallopeptidase 2 appears to be important for a variety of body functions, including bone remodeling, which is a normal process in which old bone is broken down and new bone is created to replace it.

Winchester syndrome is a rare condition whose prevalence is unknown. It has been reported in only a few individuals worldwide.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Published Date: December 01, 2013
Published By: National Institutes of Health