What Causes FTD?
Frontotemporal degeneration (FTD) is group of disorders caused by degeneration of specific parts of the brain called the frontal and/or temporal lobes. FTD brings progressive changes to behavior, personality, language, and movement.
We know today that FTD occurs when abnormal proteins accumulate and clump together in brain cells called neurons. Some of the most common proteins that are known to accumulate and lead to FTD are called tau, TDP-43, and FUS. In some cases, these accumulations result from a change, or variant, in a person’s genes. In other cases, we don’t yet know the cause.
Multiple studies since 2009 have identified that 40 percent or more of FTD are known as familial. These cases can reflect a family history of dementia, a major psychiatric condition, or progressive challenges in movement.
A subset of familial FTD cases are genetic, or hereditary, in nature. They occur when a parent passes a genetic variant associated with FTD to their child. All known genetic forms of FTD are autosomal dominant, meaning that if one parent has an FTD-associated variant, the child has a 50% chance of inheriting it. While more than a dozen genetic variants are known to cause FTD, the most common are C9orf72, GRN, and MAPT.
Why Is Learning My FTD Genetic Status Important?
Determining whether you have a genetic form of FTD can be important for a number of reasons.
Confirming an FTD Diagnosis
FTD is understood to be the most common cause of dementia for people under 60 (Knopman et al., 2011). However, it is frequently misdiagnosed, and many individuals with FTD are never given an accurate diagnosis. While genetic testing cannot by itself diagnose FTD, it can be used—along with an assessment of clinical symptoms, imaging, and other assessments—to help determine if someone has FTD or another cause for their symptoms.
Scientists are developing treatments that target specific FTD-causing genes. Only those people with changes in the targeted gene will be eligible for those treatments once available—or for the clinical trials needed to develop them. These clinical trials will not succeed unless people who know they are eligible based on their genetic status choose to take part.
In addition, some people with a family history of FTD would like to have genetic testing to better understand their risk of developing symptoms in the future. While someone without symptoms could get tested for all of the genes associated with FTD, their results may be more conclusive if there is a known genetic variant in the family, identified in someone symptomatic for FTD, that the lab can rule in or rule out.
Bear in mind that family history doesn’t always tell the whole story. FTD can present with a wide variety of symptoms, and it remains frequently misdiagnosed even today. These factors can make it difficult to have a complete understanding of prior family history of the disease. In fact, researchers have found a small but significant percentage of genetic variants associated with FTD in people without a family history.
Prior to genetic testing, AFTD strongly recommends meeting with a genetic counselor to understand the genetics of FTD and advise you on your particular situation and potential risk.