Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) is an autosomal dominant neurodegenerative disorder characterized by adult onset of one or both of these features in an affected individual, with significant intrafamilial variation. The disorder is genetically and pathologically heterogeneous (summary by Vance et al., 2006). Patients with C9ORF72 repeat expansions tend to show a lower age of onset, shorter survival, bulbar symptom onset, increased incidence of neurodegenerative disease in relatives, and a propensity toward psychosis or hallucinations compared to patients with other forms of ALS and/or FTD (summary by Harms et al., 2013). Patients with C9ORF72 repeat expansions also show psychiatric disturbances that may predate the onset of dementia (Meisler et al., 2013; Gomez-Tortosa et al., 2013).
Ranganathan et al. (2020) provided a detailed review of the genes involved in different forms of FTDALS, noting that common disease pathways involve disturbances in RNA processing, autophagy, the ubiquitin proteasome system, the unfolded protein response, and intracellular trafficking. The current understanding of ALS and FTD is that some forms of these disorders represent a spectrum of disease with converging mechanisms of neurodegeneration.
For a general phenotypic description of frontotemporal dementia, also known as frontotemporal lobar degeneration (FTLD), see 600274. For a general discussion of motor neuron disease (MND), see amyotrophic lateral sclerosis-1 (ALS1; 105400).
Genetic Heterogeneity of Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis
See also FTDALS2 (615911), caused by mutation in the CHCHD10 gene (615903) on chromosome 22q11; FTDALS3 (616437), caused by mutation in the SQSTM1 gene (601530) on chromosome 5q35; FTDALS4 (616439), caused by mutation in the TBK1 gene (604834) on chromosome 12q14; FTDALS5 (619141), caused by mutation in the CCNF gene (600227) on chromosome 16p13; FTDALS6 (613954), caused by mutation in the VCP gene (601023) on chromosome 9p13; FTDALS7 (600795), caused by mutation in the CHMP2B gene (609512) on chromosome 3p11; and FTDALS8 (619132), caused by mutation in the CYLD gene (605018) on chromosome 16q12. [from
OMIM]