A Genetic Perspective on ALS and Frontotemporal Degeneration



Partners in FTD Care
Spring 2018

Approximately 40% of affected individuals with FTD have a family history that includes at least one other relative diagnosed with a neurodegenerative disease. Their FTD is said to be familial, or hereditary. Hereditary FTD is caused by harmful gene mutations that affect proteins essential to the normal functioning and survival of brain cells. In FTD, autopsy can usually identify abnormal accumulations of either the protein tau, TDP-43 or FUS. The most common finding in ALS with FTD is TDP-43, with a small portion of cases associated with FUS.

Researchers have identified three genes that account for the majority of mutation-associated hereditary FTD cases. The most common genetic mutation in hereditary FTD and ALS is a mutation of the C9orf72 gene. Approximately 10% of all cases of ALS are familial, and of these, 25% are accounted for by mutations in C9orf72. Similarly, 10% to 25% of patients with FTD demonstrate an autosomal dominant family history. Of these, 12% demonstrate mutations in C9orf72. Presently it is unclear how the mutation in this gene leads to the pathology that causes ALS or FTD.

Because they share a common inheritable mutation, ALS with FTD can present itself in many different ways within the same family. Members of the same family may present symptoms of just ALS, or just FTD, or innumerable combinations of ALS and FTD symptoms.

For more information, visit the Genetics of FTD section of the AFTD website.

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