Penetrance

While there is intra- and interfamilial variability in the age of onset and clinical presentation, the pathogenicity of missense variants shows high penetrance and males and females are similarly affected .

Source: GeneReviews — "TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia"

Diagnostic Criteria

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. No consensus clinical diagnostic criteria for TARDBP-ALS-FTD have been published.

Suggestive Findings

TARDBP-ALS-FTD should be suspected in probands with the following clinical and neuroimaging findings and family history.

Clinical findings

Source: GeneReviews — "TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia"

Differential Diagnosis

Family history. The frequency of TARDBP pathogenic variants is about twice as high in individuals with a family history of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) (3%-4%) compared to those without a family history of these disorders (~1.5%) .

Differential diagnosis for TARDBP-ALS-FTD

Source: GeneReviews — "TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia"

Management Guidelines

No clinical practice guidelines specifically for TARDBP-related amyotrophic lateral sclerosis-frontotemporal dementia (TARDBP-ALS-FTD) have been published. Guidance provided in this section is for amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) more generally. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with TARDBP-ALS-FTD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia

Source: GeneReviews — "TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia"

Therapies Under Investigation

Unlike SOD1-ALS-FTD (see ALS Overview), for which tofersen has recently been approved by the FDA, there are no approved antisense oligonucleotide therapies for TARDBP-ALS-FTD. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, see for recommended evaluations. Table 5. Recommended Surveillance for Individuals with TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia

Source: GeneReviews — "TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia"