Is FTD genetic?
This is an important topic which concerns many patients with Frontotemporal dementia (FTD) and their families. Here, we try to address the main issues frequently raised in the clinical practice.
Almost a third of patients with FTD have a family history of dementia, if you include relatives with any sort of dementia coming on at any age. True familial FTD, however, is much rarer, accounting for about 10 -15% of cases.
As with other dementias, it is important to distinguish patients with a likely genetic basis and those with a co-incidental family history. In short, FTD patients with other family members diagnosed with younger onset dementia have a greater chance of having a gene mutation. Familial FTD is often defined as having two, or more, affected family members who have been affected by dementia of younger onset type (in the past an accurate distinction between FTD and other dementia was rarely possible). Motor Neurone Disease (MND) is included within this spectrum as FTD and MND are related, both at the cognitive and pathological level (see Overlap with MND). Patients with no family history of FTD are referred to as sporadic cases.
The diagnosed clinical variant of FTD is also an important factor to consider. Genetic factors seem less common in some forms of FTD. For instance, the vast majority of Semantic Dementia (SD) cases are sporadic, whereas the behavioural variant (bv) form, and the variant with Motor Neurone Disease features, are more often familial.
The genetic basis of FTD is not fully understood and is a topic of active research. A number of genes have been identified over the past few years on chromosomes 3, 9 and 17, although only two are common. The first gene, on chromosome 17, codes for the microtubule-associated protein tau (MAPT); mutations of the tau gene cause FTD with associated clinical features of Parkinson disease and tau-positive inclusions in the brain. The second gene, also on chromosome 17, discovered in 2006, codes for progranulin (PGN); mutations of the progranulin gene give rise to FTD associated with ubiquitin positive inclusions in nerve cells. Both the tau and PGN gene mutations are inherited in an autosomal dominant pattern. This means that each child of someone with the tau or PGN mutation has a 50% likelihood of inheriting the mutation. Those with the mutation are destined to develop the dementia. Together, the tau and PGN gene mutations account for about half of the cases of familial FTD. This means that there is currently a 50 – 50 chance of finding a mutation in someone with familial FTD, further, there are other responsible genes yet to be discovered.
Studies have shown that the likelihood of having a gene mutation, if there is no family history of dementia (or Motor Neurone Disease), is extremely low. We therefore do not recommend gene screening in sporadic cases. Gene screening should be considered for patients with familial FTD after discussion with the person, their family or both. It may be recommended for first degree relatives of people with familial FTD, but only after counselling by an appropriately trained person, typically in a medical genetic department, to ensure that those tested realise the implications of testing positive. This is not something to be undertaken lightly. It is recommended only in cases when a gene mutation has already been found in the person with FTD, or sometimes if there is a strong family history of possible FTD (two or more affected members), but the affected members have deceased before a mutation was established.
