Introduction:
Frontotemporal dementia with parkinsonism-17 is part of a group of brain disorders characterized by the loss of neurons (nerve cells). It is associated with frontotemporal degeneration, that is, the degeneration of the frontal and temporal lobes of the brain due to the loss of neurons in that area. The loss of these neurons affects that individual's behavior, personality, movement, and language. The disease starts showing symptoms in the fourth or fifth decade of life, and affected individuals survive for not more than five to ten years after the appearance of the symptoms. Frontotemporal dementia is an autosomal dominant disorder.
What Are the Clinical Features of Frontotemporal Dementia With Parkinsonism-17?
Frontotemporal dementia with parkinsonism-17 (FTDP-17) is a neurodegenerative disorder that has three cardinal symptoms such as:
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Motor symptoms.
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Behavioral changes.
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Cognitive impairment.
Behavioral Changes: Changes in the personality and behavior of a person are often the earliest signs of the disorder. They start losing appropriate responses, lose inhibition, become restless, neglect personal hygiene, and lose overall interest in activities they once enjoyed.
Motor Symptoms: These patients will require more help with personal needs and their daily activities as their motor activities will start reducing with the onset of the disease.
Cognitive Impairment: Neurodegeneration affects cognitive functions such as planning, concentration, and judgment. They may suffer from hallucinations and delusions, as some may develop psychiatric symptoms. They might not be able to judge their actions as socially appropriate or unacceptable.
Speech Impairment: These patients may start confusing one word with another (semantic paraphasias) as they develop problems with language and speech. The problems with communication worsen over time, eventually even losing their ability to communicate.
Parkinsonism: The affected individuals develop features of parkinsonism such as rigidity, tremors, and bradykinesia (unusually slow movements). These features also worsen over time, and they become unable to walk. Additionally, they have problems with eye movement, such as difficulty moving eyes up and down (gaze palsy) and rapid abnormal movements of the eyes (saccades).
Inheritance: It is an autosomal dominant disorder; that is, even if only one copy of the altered gene is affected, the disease can be expressed.
It is also called
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Familial Pick's disease.
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Wilhelmsen-Lynch disease.
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Disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC).
What Causes Frontotemporal Dementia With Parkinsonism-17?
Frontotemporal dementia with parkinsonism-17 is caused by a mutation in the gene called MAPT, which is located on chromosome 17. This gene is responsible for the coding of the protein tau, which is found in the nervous system and neurons of the brain. The normal structure and function of the tau protein are disrupted if the MAPT gene is mutated. This leads to abnormal clumps within neurons and brain cells. This leads to the death of brain cells. (It is unclear how the clumps lead to cell death). The cells in the temporal and frontal lobes of the brain gradually fail in this disease. The frontal lobes are responsible for planning, judgment, reasoning, and problem-solving. The temporal lobe handles speech, memory, hearing, and emotion.
Tauopathies are a group of diseases associated with abnormality of the tau protein, and Frontotemporal dementia with parkinsonism-17 is one of the tauopathies. Tau is found in neurons and stabilizes the microtubules.
How to Diagnose Frontotemporal Dementia With Parkinsonism-17?
Frontotemporal dementia with parkinsonism is a rare but autosomal dominant disorder that occurs due to a mutation in the gene on chromosome 17. It can be suspected if more than one of the following symptoms is present:
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Neuropsychiatric symptoms worsen, such as behavioral abnormality, personality disorder, or dementia.
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Neurological symptoms appear between the thirties and forties.
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Seizures that are not controlled by anticonvulsants.
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Speech difficulties worsen with time.
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Symptoms associated with parkinsonism such as rigidity, bradykinesia, tremors, postural instability, and poor response to therapy. These patients fall frequently and have difficulty in eye movements.
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Diagnostic methods include genetic analysis of the genes along with the analysis of clinical features. Computed tomography (CT) and magnetic resonance imaging (MRI) can eliminate other differential diagnoses such as brain abscess, tumor, or hydrocephalus. These imaging modalities also help to identify atrophy in the frontal and temporal lobes.
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Laboratory studies are generally normal. Electroencephalography (EEG) shows normal results initially, and only when the disease advances does it show variations.
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Genetic counseling. Since this disease is autosomal dominant in inheritance, affected individuals should be advised about the chance of passing the genetic disorder on to their offspring. There is a 50 % chance that an individual with the disorder can have a child with the abnormal gene. Although it is not necessary that the individual may express the same clinical features, genetic testing can be done to determine if the gene mutations are present. The clinical features vary between individuals depending on the penetration of the mutation.
What Are the Treatment Options for Frontotemporal Dementia With Parkinsonism-17?
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As most patients do not respond favorably to levodopa treatment, there are no curative treatments available. The patient is managed by providing symptomatic treatment and palliative care.
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Physical therapy is useful to manage motor symptoms and help preserve mobility and reduce the risk of falling. It also enables the patient to continue performing daily tasks.
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Stool softening is administered for constipation.
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For patients with psychosis, Clozapine or Quetiapine may be helpful.
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Speech therapy is useful for speech and language impairment.
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If the patient develops depression, antidepressants are given.
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In palliative or bed-ridden patients, water beds or air beds should be used, and they should be frequently repositioned.
What Is the Prognosis of Frontotemporal Dementia With Parkinsonism-17?
Prognosis, like the symptoms, varies between individuals. It is a slowly progressive disease. The onset of symptoms and identification may take time, and the rate of regression depends on the family history. The life expectancy ranges from several months to several years. Some cases may have a life expectancy of up to two decades. The prognosis is worsened by associated problems that may arise, such as injuries due to falls or urinary tract infections.
Conclusion:
Frontotemporal dementia with parkinsonism-17 is a rare genetic disorder that arises due to the mutation of the gene. This mutation leads to an abnormality in the tau protein, which affects the nerve cells in the frontal and temporal lobes of the brain. The patient develops symptoms in the third or fourth decade of life, which progressively worsens. The symptoms include motor impairment, speech problems, and parkinsonism-related symptoms. Management is based on the symptoms expressed by the patients.
