Paganini-Miozzo syndrome is caused by changes (variants) in a gene called HS6ST2, which is located on the X chromosome. This gene helps the body make and modify heparan sulfate, a substance that is important for how cells communicate with each other, especially during brain and eye development.
So far, only a very small number of children with this condition have been reported. In all reported cases, the genetic change was a missense variant, meaning that one “letter” in the DNA code was changed and this led to the substitution of one building block of the protein. These changes are thought to reduce or alter the normal function of the HS6ST2 protein.
Laboratory studies on some of these variants showed that the altered protein may work less well, may be less stable, or may not be processed normally inside the cell. Doctors believe that this can disturb important signals needed for normal development, particularly in the brain and the eyes. This may help explain features such as developmental delay, learning difficulties, seizures, and vision problems.
Because this condition is linked to the X chromosome, it usually affects boys more severely. Mothers can s carry the genetic change without having symptoms. Genetic testing can confirm the diagnosis and can help families understand the chance of the condition happening again in the family.
HS6ST2