There is a strong family history of a familial disorder in up to 40% of individuals with Frontotemporal degeneration (FTD). A genetic cause can be identified in up to 20% of Frontotemporal degeneration cases. In these cases, there is a detectable genetic cause that can be seen in the individual’s DNA. It is important to keep in mind that the majority of Frontotemporal degeneration is not genetic, meaning that 60% or more of FTD cases do not have a genetic cause. Research is still ongoing to understand and define the non-genetic causes of FTD .
The overall symptom profiles of genetic and non-genetic Frontotemporal degeneration are identical. The biggest clue to a genetic cause is family history. A patient with a family history that includes many relatives with FTD or other neurodegenerative diseases is more likely to have a genetic cause than a patient with no known family history of neurodegenerative diseases. The Penn Frontotemporal Degeneration Center has a genetic counselor available to help document and interpret family history information, as well as provide further information about the genetic testing options for FTD.
There are several specific genes associated with Frontotemporal degeneration or FTD related disorders. All human beings have these genes, as each gene carries specific instructions that the body needs in order to function correctly. Moreover, we have 2 copies of each gene, as one copy is inherited from the mother and one copy from the father. When there is a change in the gene (this is referred to as a mutation), this changes the instructions and consequently can lead to disease. A genetic testing laboratory can check a gene to see if there are any disease-causing mutations. A genetic test typically involves a small sample of blood, but sometimes the testing can be done on an alternative sample, such as saliva. The University of Pennsylvania has one of a small number of certified laboratories in the US that can test for the most common genes implicated in Frontotemporal degeneration . We also have a research laboratory that tests for all of the genes that have been associated with FTD.
The known genetic causes of Frontotemporal degeneration all have autosomal dominant inheritance. “Autosomal” refers to the first 22 pairs of chromosomes, which are identical in both males and females. Therefore, both genders have an equal chance of being affected if a mutation is present on a gene in an autosomal chromosome. “Dominant” inheritance means that only one copy of a gene has to have a mutation to cause disease. Typically, the copy of the gene with the mutation is inherited from one of the parents, and most individuals with an autosomal dominant condition will have a family history of the disease. A child of a person with a dominant mutation has a 50% chance of inheriting the copy of the gene with the mutation and a 50% chance of inheriting the copy of the gene without the mutation.
The majority of Frontotemporal degeneration patients with a genetic cause have a mutation occurring in one of the following genes:
For more detailed information about these genes, please see the downloadable booklet “Understanding the Genetics of FTD” .
Three additional genes that have been associated with very rare FTD cases:
The Penn FTD Center has a full-time genetics counselor who can discuss the options for helping to manage Frontotemporal degeneration . Our genetics program has the capacity to detect genetic status in family members. On-going studies are developing algorithms for helping with prognosis. With the development of treatment trials, individuals who are carriers of a mutation can participate in these trials, and asymptomatic carriers of a mutation may be able to delay or even prevent the emergence of symptomatic FTD.
Researchers at the Penn FTD Center are studying the mechanisms of disease associated with inherited forms of Frontotemporal degeneration. This is crucial to the development of treatments of FTD. We are also searching for genes causing Frontotemporal degeneration that remain to be discovered.
We are also interested in discovering genetic factors that can influence the risk or progression of FTD symptoms, as well as genetic factors that might help to predict an individual’s response to a certain treatments or medications. Genetic factors such as these can be very difficult to find and it can take thousands of DNA samples in order to make these types of discoveries.
A majority of individuals withFrontotemporal degeneration do not have a genetic cause; these individuals have sporadic Frontotemporal degeneration. Studies of genetic mechanisms of disease in FTD can teach us how to improve diagnostic accuracy in sporadic FTD. Moreover, factors related to prognosis and response to treatment interventions in genetic FTD may contribute to prognosis and treatment response in sporadic FTD.