Meyahealth
Home
ENES
HomeGeneticsConditionsWinchester syndrome
Back to Conditions
Winchester syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Conditions

Winchester syndrome

Winchester syndrome is a rare inherited disease characterized by progressive loss of bone tissue, particularly in the hands and feet, leading to pain, limited movement, and increased fracture risk, alongside potential skin and eye abnormalities.

Description

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.

In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.

Some people with Winchester syndrome have skin abnormalities including patches of dark, thick, and leathery skin. Other features of the condition can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), gingival hypertrophy, heart abnormalities, and distinctive facial features that are described as "coarse."

Frequency

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

Causes

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 survival, 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.

Mutations in the MMP14 gene alter matrix metallopeptidase 14 so that less of the enzyme is able to reach the cell surface. As a result, not enough of the enzyme is available to break down components of the extracellular matrix and activate matrix metallopeptidase 2. It is unclear how a shortage of this enzyme leads to the signs and symptoms of Winchester syndrome. It is possible that a loss of matrix metallopeptidase 2 activation somehow disrupts the balance of new bone creation and the breakdown of existing bone during bone remodeling, causing a progressive loss of bone tissue. How a reduced amount of matrix metallopeptidase 14 leads to the other features of Winchester syndrome is unknown.

Learn more about the gene associated with Winchester syndrome

  • MMP14

Inheritance

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.

Other Names

  • Winchester disease
  • WNCHRS

MEDICAL ENCYCLOPEDIA

  • Genetics

Understanding Genetics

  • What is the prognosis of a genetic condition?
  • How can gene variants affect health and development?
  • What does it mean if a disorder seems to run in my family?
  • What are the different ways a genetic condition can be inherited?
  • How are genetic conditions treated or managed?

Frequently Asked Questions

Patients should be closely monitored for increased fracture risk due to osteopenia and osteoporosis, requiring regular bone density scans. Cardiac abnormalities, corneal opacity, and gingival hypertrophy also require periodic evaluation by specialists. Regular follow-ups with a multidisciplinary team, including orthopedists, rheumatologists, ophthalmologists, and cardiologists, are essential to manage the various manifestations and prevent severe complications.
Treatment focuses on managing symptoms and preventing complications. This typically includes pain management with medications, physical therapy to maintain joint mobility and strength, and sometimes orthopedic interventions for severe joint deformities or fractures. Bisphosphonates or other bone-modifying agents may be considered to help slow bone loss, though their effectiveness can vary.
Winchester syndrome is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated MMP14 gene (one from each parent) to develop the condition. Parents who are carriers (have one mutated gene copy) typically do not show symptoms but can pass the gene to their children. Genetic counseling is recommended for affected families to understand inheritance risks and discuss family planning options.
Diagnosis often involves a combination of clinical evaluation of symptoms like bone pain, limited movement, and skin changes, along with X-rays to identify characteristic bone loss patterns, particularly in the hands and feet. Genetic testing for mutations in the MMP14 gene is crucial to confirm the diagnosis and differentiate it from similar disorders like MONA.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ