Genetic screening in sporadic ALS and FTD

Abstract

The increasing complexity of the genetic landscape in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) presents a significant resource and physician training challenge. At least 10% of those diagnosed with ALS or FTD are known to carry an autosomal dominant genetic mutation. There is no consensus on what constitutes a positive family history, and ascertainment is unreliable for many reasons. However, symptomatic individuals often wish to understand as much as possible about the cause of their disease, and to share this knowledge with their family. While the right of an individual not to know is a key aspect of patient autonomy, and despite the absence of definitive therapy, many newly diagnosed individuals are likely to elect for genetic testing if offered. It is incumbent on the practitioner to ensure that they are adequately informed, counselled and supported in this decision.

Keywords: ALS; C9ORF; FRONTOTEMPORAL DEMENTIA; GENETICS.

Figure 1

Upper panel: Comparison of proportions of monogenic causes of ALS in those reporting a family history of ALS versus apparently sporadic cases. Lower panel: Comparison of proportions of monogenic causes of FTD in those reporting a family history of dementia versus apparently sporadic cases. ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia.