Case Report Co-Authored by AFTD Board Member Highlights Varying Presentations of FTD-GRN

Graphic: Case report co-authored by AFTD board member highlights varying presentations of FTD-GRN

A case report recently published in the journal Clinical Parkinsonism & Related Disorders highlights how even between people with the same variant of genetic FTD caused by a GRN mutation (FTD-GRN), the presentation of the disease can vary greatly. The study was co-authored by AFTD Board member and assistant professor of medicine at Johns Hopkins University School of Medicine Halima Amjad, MD, PhD.

The case report summarizes the experiences of a 73-year-old woman who was first evaluated for symptoms resembling atypical parkinsonism. She reported difficulties with the use of her left arm and a progressive history of balance issues, and required assistance with several basic daily activities like dressing herself. Her family noted that she had become less engaged with them, and had become more apathetic and withdrawn. The woman had previously undergone PET and MRI scans, which revealed distinct atrophy patterns in several areas of the brain.

The woman was initially diagnosed with Parkinson’s disease and given medicines typically used to treat it, though she experienced no benefits and had issues with vertigo after the doctors raised the dosage.

Researchers consulted the woman’s medical history, finding that FTD had been diagnosed in her mother and sister, with her sister showing communication-based symptoms consistent with primary progressive aphasia (PPA), and that her maternal grandfather and uncle had a history of unspecified dementia.

Because of the woman’s family history and the possibility of a genetic link, the researchers recommended genetic testing. Months later, after the woman was placed in a memory care facility due to her symptoms, genetic testing confirmed a GRN gene mutation.

Despite her sister’s symptoms presenting as PPA, researchers found that the woman’s symptoms met the clinical criteria for probable corticobasal syndrome (CBS), an FTD disorder that primarily affects movement. CBS symptoms are often described as “atypical parkinsonism” because of the decline in motor function they cause, which is more commonly associated with Parkinson’s, which helped explain her initial misdiagnosis.

Researchers note that FTD-GRN can have a range of presentations across the FTD spectrum and can, at times, have a mixed pathology. People with FTD-GRN can present with symptoms consistent with behavioral variant frontotemporal degeneration or one of the three PPA variants; in rare instances, GRN mutations might also present in a manner consistent with Lewy body dementia. Roughly 40% of people with GRN mutations experience movement-based difficulties following the development of behavioral symptoms, such as the woman featured in the study. Those with movement-based difficulties typically involve symptoms consistent with CBS or progressive supranuclear palsy.

The authors highlight the importance of family medical history in their analysis, which demonstrates just how diverse the presentation of a single mutation can be across multiple generations. They note that it is important to keep FTD-GRN in mind as a potential diagnosis when people have mixed presentations, including parkinsonism and speech and behavioral changes.

Did you know that there are other gene variants that can cause FTD? Check out the FTD Genetics and You page to learn more.

If you’re worried that your family may be at risk for genetic FTD, genetic testing can help you determine if you carry a disease-causing variant. Visit the About Genetic Testing page to learn about the risks and benefits of genetic testing.

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