Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia

Vaishnavi Manohar  1 , Leon Crowley  1 , Jemeen Sreedharan  1
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].
Affiliations
Free Books & Documents
Review

TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia

Vaishnavi Manohar et al.
Free Books & Documents

Excerpt

Clinical characteristics: In this GeneReview, TARDBP amyotrophic lateral sclerosis-frontotemporal dementia (TARDBP-ALS-FTD) refers to the spectrum of phenotypes caused by pathogenic variants in TARDBP, the gene encoding TDP-43. The phenotypic spectrum encompasses pure (i.e., without other neurologic findings) amyotrophic lateral sclerosis (ALS; most common), pure (i.e., without other neurologic findings) frontotemporal dementia (FTD; rare), a combination of ALS and FTD, and atypical neurologic phenotypes (very rare). Individuals with the same TARDBP pathogenic variant (even within the same family) may have clinical features that vary in both type and severity. Common manifestations are dysarthria and dysphagia; less common manifestations can include parkinsonism, cognitive deterioration, and behavioral and psychological manifestations of dementia. Life expectancy for TARDBP-ALS is highly variable and mainly associated with an individual's clinical features; overall disease duration averages three to five years. For TARDBP-FTD, disease duration averages one to 16 years.

Diagnosis/testing: The diagnosis of TARDBP-ALS-FTD is established in a proband with suggestive findings and most commonly a heterozygous pathogenic (or likely pathogenic) variant in TARDBP identified by molecular genetic testing. Rarely, homozygous pathogenic (or likely pathogenic) variants in TARDBP have been reported.

Management: Treatment of manifestations: There is no cure for TARDBP-ALS-FTD. Individuals benefit from multidisciplinary supportive care to improve quality of life, maximize function, and reduce complications. This can include care by specialists in neurology, physiotherapy, occupational therapy, speech-language therapy, nutrition, respiratory therapy, pulmonology, psychology, social work, genetic counselling, palliative care, and special nursing.

Surveillance: Frequent monitoring of existing manifestations, the individual's response to supportive care, and the emergence of new manifestations by the treating clinicians is recommended.

Genetic counseling: TARDBP-ALS-FTD is inherited in an autosomal dominant manner. About half of individuals diagnosed with TARDBP-ALS-FTD have an affected parent. Each child of an individual with TARDBP-ALS-FTD has a 50% chance of inheriting the TARDBP pathogenic variant. Once a TARDBP pathogenic variant has been identified in an affected family member, predictive testing for at-risk relatives and prenatal and preimplantation genetic testing for the presence of the TARDBP pathogenic variant are possible. (Note: Because the clinical presentation of TARDBP-ALS-FTD may differ among heterozygous family members, accurate prediction of future possible clinical manifestations in an individual found to have a familial TARDBP pathogenic variant is not possible.)

PubMed Disclaimer

Similar articles

  • C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis.
    Gossye H, Engelborghs S, Van Broeckhoven C, van der Zee J. Gossye H, et al. 2015 Jan 8 [updated 2020 Dec 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2015 Jan 8 [updated 2020 Dec 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 25577942 Free Books & Documents. Review.
  • MAPT-Related Frontotemporal Dementia.
    Rohrer J, Ryan B, Ahmed R. Rohrer J, et al. 2000 Nov 7 [updated 2022 Aug 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2000 Nov 7 [updated 2022 Aug 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301678 Free Books & Documents. Review.
  • WARS2 Deficiency.
    Mroczek M, Busra A, Houlden H, Efthymiou S, Nagy S. Mroczek M, et al. 2023 Oct 12. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2023 Oct 12. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 37824696 Free Books & Documents. Review.
  • Ataxia-Telangiectasia.
    Veenhuis S, van Os N, Weemaes C, Kamsteeg EJ, Willemsen M. Veenhuis S, et al. 1999 Mar 19 [updated 2023 Oct 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 1999 Mar 19 [updated 2023 Oct 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301790 Free Books & Documents. Review.
  • CSF1R-Related Disorder.
    Dulski J, Sundal C, Wszolek ZK. Dulski J, et al. 2012 Aug 30 [updated 2024 Apr 4]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2012 Aug 30 [updated 2024 Apr 4]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 22934315 Free Books & Documents. Review.
See all similar articles

References

    1. Abel O, Powell JF, Andersen PM, Al-Chalabi A. Credibility analysis of putative disease-causing genes using bioinformatics. PLoS One. 2013;8:e64899. - PMC - PubMed
    1. Acosta-Uribe J, Aguillón D, Cochran JN, Giraldo M, Madrigal L, Killingsworth BW, Singhal R, Labib S, Alzate D, Velilla L, Moreno S, García GP, Saldarriaga A, Piedrahita F, Hincapié L, López HE, Perumal N, Morelo L, Vallejo D, Solano JM, Reiman EM, Surace EI, Itzcovich T, Allegri R, Sánchez-Valle R, Villegas-Lanau A, White CL, 3rd, Matallana D, Myers RM, Browning SR, Lopera F, Kosik KS. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects. Genome Med. 2022;14:27. - PMC - PubMed
    1. Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, Hardiman O, Kollewe K, Morrison KE, Petri S, Pradat PF, Silani V, Tomik B, Wasner M, Weber M, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. Eur J Neurol. 2012;19:360–75. - PubMed
    1. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351:602–11. - PubMed
    1. Borghero G, Floris G, Cannas A, Marrosu MG, Murru MR, Costantino E, Parish LD, Pugliatti M, Ticca A, Traynor BJ, Calvo A, Cammarosano S, Moglia C, Cistaro A, Brunetti M, Restagno G, Chiò A. A patient carrying a homozygous p.A382T TARDBP missense mutation shows a syndrome including ALS, extrapyramidal symptoms, and FTD. Neurobiol Aging. 2011;32:2327.e1–5. - PMC - PubMed

LinkOut - more resources