MAPT- Related Frontotemporal Dementia

Excerpt

Clinical characteristics: The spectrum of clinical manifestations of MAPT-related frontotemporal dementia (MAPT-FTD) has expanded from its original description of frontotemporal dementia and parkinsonian manifestations to include changes in behavior, motor function, memory, and/or language. A recent retrospective study suggested that the majority of affected individuals have either behavioral changes consistent with a diagnosis of behavioral variant FTD (bvFTD) or, less commonly, a parkinsonian syndrome (i.e., progressive supranuclear palsy, corticobasal syndrome, or Parkinson disease). Fewer than 5% of people with MAPT-FTD have primary progressive aphasia or Alzheimer disease. Clinical presentation may differ between and within families with the same MAPT variant. MAPT-FTD is a progressive disorder that commonly ends with a relatively global dementia in which some affected individuals become mute. Progression of motor impairment in affected individuals results in some becoming chairbound and others bedbound. Mean disease duration is 9.3 (SD: 6.4) years but is individually variable and can be more than 30 years in some instances.

Diagnosis/testing: The diagnosis of MAPT-FTD is established in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in MAPT identified by molecular genetic testing.

Management: Treatment of manifestations: There is no cure for MAPT-FTD. Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This can involve multidisciplinary care that often includes a neurologist, specially trained nurses, speech-language pathologist or therapist, physical therapist, occupational therapist, nutritionist, psychiatrist/psychologist, social worker, and genetic counselor.

Surveillance: To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, routine evaluations by multidisciplinary specialists are recommended.

Genetic counseling: MAPT-FTD is inherited in an autosomal dominant manner. Most individuals diagnosed with MAPT-FTD have an affected parent with the clinical features of FTD and/or parkinsonism; however, because of the late onset and relatively rapid course of the disease, the affected parent often dies before onset of the disease in the offspring. A proband with MAPT-FTD may have the disorder as the result of a de novo pathogenic variant; such variants have been reported but are thought to be rare. Once the MAPT pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.