Genetic causes of frontotemporal degeneration

J Geriatr Psychiatry Neurol. 2010 Dec;23(4):260-8. doi: 10.1177/0891988710383574. Epub 2010 Oct 11.


The purpose of this review is to provide a comprehensive update on the genetic causes of frontotemporal lobar degeneration (FTLD). Approximately 40% to 50% of patients diagnosed with FTLD have a family history of a ''related disorder,'' whereas 10% to 40% have an autosomal dominant family history for the disease. At this time, mutations occurring in 2 independent genes located on the same chromosome (MAPT and GRN) have been shown to cause the majority of cases of autosomal dominant FTLD. Specific genetic, molecular, pathological, and phenotypic variations associated with each of these gene mutations are discussed, as well as markers that may help differentiate the 2. In addition, 3 relatively rare, additional genes known to cause familial FTLD are examined in brief. Lastly, genetic counseling issues which may be important to the community clinician are discussed.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Animals
  • Brain / pathology*
  • Cell Cycle Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Endosomal Sorting Complexes Required for Transport / genetics*
  • Family
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / pathology
  • Frontotemporal Lobar Degeneration / psychology
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Progranulins
  • Tomography, X-Ray Computed
  • Valosin Containing Protein
  • tau Proteins / genetics*


  • CHMP2B protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Nerve Tissue Proteins
  • Progranulins
  • tau Proteins
  • Adenosine Triphosphatases
  • Valosin Containing Protein