Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review

Abstract

Objective: To report the clinical manifestation and genetic characteristics of a patient having frontotemporal dementia (FTD) with abnormal behavior and unstable walking.

Methods: The clinical and imaging features of a patient who was eventually diagnosed with FTD were analyzed. The patient's neuropsychological, PET-CT, electromyography, and genetic data were collected. Furthermore, the patient's blood samples were examined for FTD-related genes.

Results: The patient was a 52-year-old man with hidden onset. The symptoms progressed gradually, presenting with abnormal behaviors, including repeated shopping, taking away other people's things, constantly eating snacks, and frequently calling friends at night. The patient also exhibited executive dysfunction, such as the inability to cook and multiple driving problems, e.g., constantly deviates from his lane while driving. In addition, the patient showed personality changes such as irritability, indifference, and withdrawal, as well as motor symptoms, including unstable walking and frequent falls when walking. Brain magnetic resonance imaging revealed hippocampal sclerosis along with widening and deepening of the bilateral temporal lobe sulcus. Brain metabolic imaging via PET-CT demonstrated decreased metabolism in the bilateral prefrontal lobe, with the abnormal energy metabolism indicating FTD. Lastly, blood sample analysis detected mutations in the amyotrophic lateral sclerosis (ALS)-related GRN gene c.1352C > T (p.P451L) and ErbB4 gene c.256 T > C (p.Y86H).

Conclusion: This is the first case of heterozygous mutations in the GRN and ErbB4 genes in FTD alone. The GRN and ErbB4 genes are likely to be important in the pathogenesis of FTD, expanding the common genetic profile of ALS and FTD.

Keywords: Abnormal behavior; Behavioral variant frontotemporal dementia; GRN and ERBB4 genes; Mutation; Unstable walking.

Fig. 1

Brain imaging examination showing the brain abnormalities of the patient. Bilateral hippocampal atrophy, frontotemporal lobe atrophy, and widening and deepening of the bilateral temporal lobe sulcus were observed

Fig. 2

Sequence diagram of the GRN gene mutation in the patient and his daughter. High-throughput gene testing revealed a c.1352C > T (p.P451L) heterozygous mutation in the GRN gene while no variants were detected in his daughter

Fig. 3

Sequence diagram of the ErbB4 gene mutation in the patient and his daughter. The patient had a heterozygous mutation c.256 T > C (p.Y86H) in the ERBB4 gene while no variants were found in her daughter