HFS is caused by changes (mutations) in the ANTXR2 gene, which provides instructions for making a protein that helps regulate certain substances in the body, including collagen. This protein helps maintain the structure and function of connective tissues like skin, bones, and cartilage by interacting with the extracellular matrix—the network of proteins surrounding cells. It also plays a role in forming small blood vessels and supporting basement membranes, which help organize and separate tissues. When this gene is altered, the protein does not work properly, leading to a buildup of abnormal material in the skin, joints, and other tissues.
There are different types of changes in the ANTXR2 gene, which can affect the severity of the condition:
• Some changes in the gene completely stop the protein from being made or working properly. These tend to cause more severe symptoms, including serious digestive problems and infections.
• Other changes partially affect how the protein works. These are usually linked to milder symptoms, and some individuals can live into adulthood.
Researchers have found that changes in different regions of the ANTXR2 gene influence how severe the condition is. Variation in certain areas of the gene are more likely to lead to the severe form of the condition, while changes in other areas are associated with milder symptoms.
Understanding these genetic differences helps clinicians provide better care and plan management based on the specific genetic change an individual has.
ANTXR2