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The mystery of genetic mutations: What genetic factors cause progressive myoclonic epilepsy?
Progressive myoclonic epilepsy (PME) is a group of rare inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and deterioration of neurological function. The cause of PME depends primarily on its specific type, with most PMEs caused by autosomal dominant or recessive mutations as well as mitochondrial mutations. Furthermore, the location of mutations also affects the inheritance pattern of PMEs and their therapeutic efficacy. Diagnosis of PMEs is difficult due to genetic heterogeneity and unidentified genetic mutations in some patients.
The prognosis of most PMEs is not optimistic. Individuals often need to rely on wheelchairs to carry out daily activities, or even fall into a vegetative state due to myoclonus, and their life expectancy is also shortened.
Common signs and symptoms
The most common symptom of PME is myoclonus, which may be intermittent or multifocal and can be triggered by posture, movement, and external stimuli such as light, sound, and touch. Myoclonus presents differently depending on the type of PME. In addition, generalized, tonic, paroxysmal, and atypical seizures may occur. In Lafora disease, patients suffer moments of visual blindness as well as visual hallucinations.
Once progression begins, PME has a marked decrease in neurological capacity and may lead to symptoms such as myopathy, neuropathy, cognitive decline, cerebellar ataxia, and dementia.
Diagnosis process
The diagnosis of PME relies primarily on the individual's symptoms and lack of response to antiepileptic drugs and treatments. In addition, electroencephalogram (EEG) results, genetic testing, enzyme testing, and skin and muscle biopsies can also assist in diagnosis. The diagnostic challenge is that the neurophysiological characteristics of different patients are very different, resulting in variable EEG results.
Management and Treatment
There is currently no cure for PME, and treatment focuses primarily on managing symptoms, especially myoclonus and seizures. However, treatment of symptoms is often challenging due to resistance of patients with PMEs to antiepileptic drugs. Antiepileptic drugs used include valproic acid, benzodiazepines, valproic acid, clofluthixol, etc.
Although some anti-epileptic drugs are effective in controlling symptoms, some such as vegabat can worsen symptoms, so treatment needs to be chosen carefully.
Prognosis
The prognosis for PME depends on the specific type. In the case of Lafleurosis, neurodegeneration gradually increases over a decade, eventually leading to a vegetative state and death shortly after diagnosis. However, with other types of PME, such as Unverricht-Lundborg disease, advances in antiepileptic drugs have extended patient lifespan to well beyond sixty years.
Research Progress
The rarity of PME makes specific studies difficult. In particular, it is difficult to guarantee the accuracy of double-blind studies for testing the effects of anti-epileptic drugs. Research is also ongoing into the use of oligonucleotide therapeutic strategies to replace genetic defects in patients with Unverricht-Lundborg epilepsy. However, studying the impact of AEDs has been limited due to the variable symptoms and EEG variability of PMEs.
The origin and history of PME
As early as 1822, Prichard first mentioned the relationship between myoclonus and epilepsy. Later, Lundborg proposed the name "progressive myoclonic epilepsy" in 1903, based on his studies of several Swedish families. Despite this, Unverricht-Lundborg disease was not recognized as a disease until a century later.
As our understanding of the disease deepens, scientists continue to work hard to find mutated genes and their impact on symptoms. Can this lead us to find treatments for PME in the future?
