Molecular characteristics

Many changes in the genetic code of the PCDH19 gene have been found to cause CE. Changes which affect the gene’s ability to function (and therefore cause disease) are referred to as pathogenic variants or mutations. Every person has a unique genetic code and most changes to this code do not cause disease. These non-disease-causing changes are called benign variants. When a diagnosis of CE is supported by the finding of a pathogenic variant by a molecular laboratory, the identified variation is recorded on the report from the testing laboratory.

Most individuals with CE have a pathogenic variant that is unique to their family, and therefore it can be difficult to determine if a variant is a benign (non-disease-causing) change or a pathogenic (disease-causing) change. More evidence may be required to be sure that the genetic change in PCDH19 is causing disease. Testing of other family members can be helpful and provide evidence for the variant being either benign or pathogenic. A clinical genetics service can advise on the next steps after a PCDH19 pathogenic variant is identified.

The international scientific and diagnostic community is working hard to build tools to improve our ability to determine whether a variant is disease-causing or not.