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Progressive Myoclonic Epilepsy
Progressive myoclonic epilepsy (PME) is a group of myoclonic epilepsies with the subgroups being of several diseases sharing similar features. (webmd) These shared features include any of the following: worsening of symptoms as time progresses, Autosomal recessive inheritance, mutations of gene sequences leading to inhibitions of specific protein production, and reoccurring seizures (webmd). Progressive myoclonic epilepsy differs from myoclonic epilepsies by muscle contractions (myoclonus) being a separate entity from reoccurring seizures as well as the disease progressively getting worse over time and mostly ultimately leading to death (e.com)(webmd). There are four main sub-groups of PME being Lafora disease, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fibers, and Batten disease (PME).

Lafora progressive myoclonus epilepsy
Lafora progressive myoclonus epilepsy (Lafora Disease, Lafora Body Disease) is a genetic disorder of the brain that causes reoccurring seizures and slow declination of intellectual ability (GHR). The common seizures that occur in individuals with Lafora disease include occipital seizures as well as grand mal seizures. Occipital seizures can cause hallucinations and even temporary blindness (GHR, PME). Grand mal seizures (tonic-clonic seizures) are myoclonic seizures that affect a large portion or even entirely of the individual's body, causing rigidness in the muscles, uncontrollable convulsions, and can cause the individual to fall into a state of unconsciousness (GHR). These seizures usually begin in late childhood or early adolescence, with noticeable symptoms being depression, periods of confusion, and speech difficulties (GHR). As time progresses, symptoms of some loss of intellectual ability occurs such as memory loss, slowed thought processes, and impaired judgment that make the ability to perform tasks normal for daily life very difficult (GHR). The loss of this ability takes only around one decade after the first appearance of symptoms, and the end result is death (GHR). This disease is an autosomal recessive trait, so both recessive genes from parents must be passed on and also must contain the gene mutations (GHR, PME). The specific genes that lead to Lafora disease are mutations in either the EPM2A gene or the NHLRC1 gene (GHR). The EPM2A gene is responsible for making the protein Laforin, and the mutation denies the cell ability to produce this protein (GHR). The NHLRC1 gene likewise, is responsible for making the protein malin, and the mutation in the gene makes the sequence no longer code for the protein production (GHR). Laforin and malin together help regulate glycogen production, preventing a dangerous buildup of glycogen in cells (GHR). Abnormal formations of these glycogen deposits (Lafora bodies) cannot be broken down for fuel supply in the cell, and this buildup kills nerve cells, which leads to brain dysfunction (GHR). Lafora disease generally progresses slower in individuals with NHLRC1 gene mutation as opposed to the EPM2A gene, which is a phenomenon that is not yet clearly distinguished (GHR).

Unverricht-Lundborg Disease
Unverricht-Lundborg Disease (Baltic myoclonus, Mediterranean myoclonus) is a form of myoclonus epilepsy that is first seen in children as young as six, and occurs after stimuli to light, excessive exercise, stress, and other stimuli (GHR). The seizures experienced are grand mal seizures which involve the entire body in muscle contractions, and can lead to unconsciousness in some cases (GHR). Without medication, these seizures will advance over the span of several years to become severe enough to interfere with normal daily activities such as driving and walking (GHR). In addition to this, progression of this disease may lead to slight declines of intellectual ability, involuntary rhythmic shaking, depression, difficulties with speech, and declines in coordination (e.com). This is the most common of the progressive myoclonic epilepsies, and although worldwide statistics are unknown, the disease has a prevalence in 1 in 25000 in Finland, which is where the disease is most common (GHR). Unverricht-Lundborg disease is an autosomal recessive disease, and thus is inherited (GHR). The mutated gene that causes the disease is the CSTB gene, which is responsible for coding for the cyctatin B protein. This protein is involved with decreasing the activity of the enzyme cathepsins. Cathepsins help break down certain proteins in lysosomes, and with less cyctatin B proteins, the cathepsins are thought to be able to break down important proteins in the cytoplasm (GHR). The CSTB gene is a 12 base pair sequence 5'CCC-CGC-CCC-CGC3', and this repeats only a couple of times in healthy individuals (e.com). The mutation is an extended repeat of this 12 base pair sequence, containing 30 to 100 repeats (e.com). This repeat sequence is located in the promoter region 175 base pairs upstream from the AUG initiation sequence (e.com). Treatment of this disease is shown to lighten symptoms and slow progression (e.com). The standard treatment currently available is valproic acid complimentary with clonazepam or piracetam (e.com).

Myoclonic Epilepsy with Ragged-Red Fibers
Myoclonic epilepsy with ragged-red fibers (MERRF) is a myoclonic epilepsy that affects muscle and nerve cells, and it first appears in late childhood or adolescence (GHR). The typical signs of MERRF are twitching in the muscles, progressive stiffness, and general weakness (GHR). The term 'ragged-red fibers' stems from the fact that individuals with the disease have abnormal muscle cells in design. The symptoms of MERRF include ataxia, peripheral neuropathy, recurrent seizures, loss of intellectual function, and also may develop optic atrophy and loss of hearing (GHR). Less commonly individuals develop cardiomyopathy, or short stature and abnormalities in the heart (PME). This disease is inherited by maternal inheritance because the disease is found in mitochondrial DNA (mtDNA), which is found in egg cells and not sperm cells (GHR)(PME). The specific genes that form mutations are the MT-TK, MT-TL1, MT-TH, and MT-TS1 genes, with four fifths of the mutations occurring in the MT-TK gene (PME). The mutations of the genes affect the functioning of the mitochondria to use oxygen to produce energy, and also impair the ability of producing certain proteins in the mitochondria (PME). This mostly affects the cells in the body that are high energy, which include brain and muscle cells (PME)(GHR). This is still a disease that needs further research to determine more specifically what occurs in the mitochondria of the cells (PME).

Batten Disease
Batten Disease is a form of neuronal ceroid lipofuscinoses (NCL) that is prevalent in children that first appears between the ages of 4 and 18 (GHR). The first sign of Batten disease is declination of vision which occurs normally before the age of ten, which leads to total blindness after rapid vision loss (GHR). The seizures in individuals usually begin after the beginning of vision impairments, anywhere from the ages of 5 to 18 (GHR). Individuals will also experience the declination of cognitive ability, along with behavioral and attention problems, troubles with speech, and difficulty sleeping (GHR). Another difficulty developed by affected individuals is typical issue that is shared with NCL diseases, which is the development of rigid, slow, and clumsy movement, that progresses into the inability to perform everyday tasks that is even extended to the ability to walk (GHR). In the United States, the prevalence of this disease is 1:50000 to 1:25000 individuals (GHR). This disease is an autosomal recessive disease, meaning it is passed on by the parents who both contain the mutated recessive gene (GHR). The affected gene is the CLN3 gene which codes for a protein that plays an important role in the survival of nerve cells, although the specific protein is still not known (GHR). While the role of the gene is unknown, it is expected that the mutation disrupt the functioning of lysosomes in nerve cells, making the buildup of lipopigment possible, which is a lipid that builds up abnormally in lysosomes, ultimately causing cellular death (GHR). Affected individuals usually live into their twenties, with a handful living into their thirties (GHR).