Clinical Guidance

The following genotype-phenotype correlations have been observed :

• The common variants and usually present with bvFTD.

• The variant usually presents with a parkinsonian syndrome.

• A sizeable minority of individuals with the variant present with a parkinsonism syndrome.

• The less common variants , , , , , and can present with a parkinsonian syndrome.

• The variants , , and in particular may present with episodic memory problems, and in some individuals this can be the initial presentation, with a phenotype similar to Alzheimer disease.

Source: GeneReviews — "MAPT-Related Frontotemporal Dementia"

Penetrance

MAPT-FTD is commonly thought to be a fully penetrant disorder. However, occasional reduced penetrance may exist in some families with specific MAPT variants (e.g., , and ), and may be age related.

Source: GeneReviews — "MAPT-Related Frontotemporal Dementia"

Diagnostic Criteria

No consensus clinical diagnostic criteria for MAPT-related frontotemporal dementia (MAPT-FTD) have been published. However, diagnostic criteria for features of FTD including behavioral changes (full text), corticobasal degeneration (full text), progressive supranuclear palsy (full text), and primary progressive aphasia (full text) have been published.

Suggestive Findings

MAPT-FTD should be suspected in individuals with the following clinical features, neuroimaging findings, and family history.

Clinical features

Source: GeneReviews — "MAPT-Related Frontotemporal Dementia"

Differential Diagnosis

The clinical characteristics of MAPT-related frontotemporal dementia (MAPT-FTD) significantly overlap with those of other conditions, including FTD of unknown cause, genetic FTD (e.g., GRN- and C9orf72-related FTD), FTD spectrum disorders (e.g., corticobasal syndrome and progressive supranuclear palsy), as well as non-FTD spectrum disorders (Parkinson disease, Alzheimer disease, and Huntington disease). This clinical overlap makes it difficult to predict which family has MAPT-FTD by clinical presentation alone. Around 30% of individuals with FTD have familial FTD (i.e., a positive family history of dementia, usually with autosomal dominant inheritance). lists the most common genes associated with familial FTD. Note: On rare occasions individuals with MAPT-FTD may be seen initially by psychiatrists for mental health issues that resemble schizophrenia. However, schizophrenia typically initially manifests in the teenage years to age 30 years, while onset of MAPT-FTD is typically between ages 30 and 60 years. Table 3. Genes of Interest in the Differential Diagnosis of MAPT-Related Frontotemporal Dementia

Management Guidelines

No clinical practice guidelines for MAPT-related frontotemporal dementia (MAPT-FTD) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MAPT-FTD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. MAPT-Related Frontotemporal Dementia: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "MAPT-Related Frontotemporal Dementia"

Therapies Under Investigation

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 — "MAPT-Related Frontotemporal Dementia"

Surveillance Guidelines

Table 6. MAPT-Related Frontotemporal Dementia: Recommended Surveillance

Source: GeneReviews — "MAPT-Related Frontotemporal Dementia"