Myotonic Dystrophy : A Disorder That Affects Multiple Systems

Autosomal recessive inheritance is the third type known to cause muscular dystrophy, whereas both parents are carriers of the defective gene. For this reason the offspring have a 25% chance of being affected with both malformed genes, resulting in them being affected. The chance increases with cousin marriages.

Duchenne Muscular Dystrophy is the most common muscular dystrophy disorder. In the United States DMD affects 1 in 3,500 males. 2/3 of those cases are passed down for the mothers and 1/3 are random mutations. Internationally the statistics are similar. (Medscape, 2015)

Duchenne muscular dystrophy is a gender-linked inherited disorder. To illustrate, males only have one X chromosome, therefore they do not have a second X chromosome to make up for the damaged gene. Females can only become carriers of the disease, as females have a second X chromosomes to make up for the damaged gene.

Genetics is a key factor in potentially developing a form of muscular dystrophy, as it is caused by a gene that protects muscle fibers suddenly becoming defective. However, this particular genetic mutation can abruptly occur while an embryo is still developing in the egg of the mother. Muscular dystrophy can occur in an individual of any age, sex, or race. The most common form of MD diagnosed, Dechenne, is most often found in males of a youg age. However, family history of the disease is the biggest risk factor associated with developing it.

Autosomal dominant LGMD occur less often than recessive dominant LGMD. In the metabolism myotilin gene mutations occur, it may be due to a deficiency of vitamin B12, vitamin E, folate or exposures to nitrous oxide. LGMD 1A disease normally occurs from the age 42 to 77, and develops in the same areas (hip, shoulder and back) however, it could spread to the leg muscles. Due to the fact that myotilin gene is mutated, it causes focal myofibrillar destruction to occur, and this results in intracytoplasmic deposits to float around in the blood stream. In one case study done in Barcelona in 2011, there were 13 patients who were all diagnosed with myotilin gene mutation disease. The results showed that the deposits of myofibrillar became immune to myotilin and cluster up the vacuoles and interfere with the Z-lines. Overall the study revealed that each patient shared the same phenotypic characteristics, LGMD 1A and myofibrillar myopathy variations which emphasizes that LGMD is a developing neuromuscular disorder (Montse,

The cause of Duchenne Muscular Dystrophy is the occurrence of mutations in the Dystrophin (DMD) gene. The cytogenetic location off the DMD gene is Xp21.2; meaning at location 21.2 on the short arm of the X chromosome from base pair 31,119,219 to base pair 33,339,609. DMD is the biggest human gene currently known and instructs for the production of a 427 kDa protein by the same name. The dystrophin protein is part of the dystrophin associated protein complex which is expressed at the sarcolema and anchors muscle cellcytoskeletons to the extracellular matrix in skeletal and cardiac muscle,

DMD is caused by a mutation in the X-linked dystrophin gene, which results in a dysfunctional dystrophin protein. Dystrophin is a cytoskeletal protein that provides mechanical stability to muscle cells by connecting the muscle sarcolemma to the basal lamina of the extracellular matrix (ECM), and without it there, the muscle cells typically undergo a process of degeneration and regeneration. This process is limited by the survival of satellite cells present since satellite cells can only undergo mitosis a limited amount of times. Sarcolemma instability typically results in excess intracellular amounts of both sodium and calcium, which causes ATP depletion and mitochondrial uncoupling (Horn & Schleip, 2012). Satellite cells only have a limited number times they can undergo mitosis, and once a patient can no longer generate healthy muscle cells, the patient will typically experience cell death. This cell death and necrosis usually

Duchenne muscular dystrophy (DMD) is caused by a mutated gene in the X chromosome. This flawed genes is passed on by the mother. However, most carrier of the gene do not show signs or symptoms of the disease. The The flawed gene causes the improper production of the protein dystrophin which is accompanied by “defective dystrophin-glycoprotein complex (DGC) in the sarcolemma and leads to progressive muscle degeneration” (Nakamura & Takeda, 2011). The Dystrophin protein is vital in providing a muscle integrity. Therefore, the absence of dystrophin production can lead to muscled atrophy.

Duchenne Muscular Dystrophy is one of the most severe yet common cases of Muscular Dystrophy that occurs mainly in boys of younger age. Guillaume Benjamin Amand Duchenne, who was a French neurologist, was the first to discover this disorder in the 1860s (Emery, 2008, pp. 25). This disease is an X-linked disorder which affects the skeletal system, and causes rapid muscular weakness and heart muscle problems. It’s stated that 1 out of every 3,600 males will be diagnosed with Duchenne Muscular Dystrophy (Bushby, 2009, pp.1). According to the Muscular Dystrophy Association, symptoms usually begin to show between the ages of 3 to 5 years old. (pp. 1) Some of the symptoms may include delayed in walking, regularly falling, learning difficulties,

This protein may play a role in the communication within cells, especially those of the heart, brain and skeletal muscles. It is believed that the protein is involved in the communication between cells and regulates the production and function of important structures inside muscles cells by interacting with other proteins. The DMPK gene is located on the long arm of chromosome 19 at position 13.3. It is between base pairs 45,769,708 and 45,782,556 making it 12848 base pairs long. It consists of a trinucleotide repeat of the nucleotide sequence CTG. Meaning that the nucleotides CTG are repeated multiple times. In a normal DMPK protein the number of CTG repeats ranges from 5-34. The mutation that causes myotonic dystrophy is known as trinucleotide repeat expansion, meaning it increases the number of times CTG is repeated in the gene. People with myotonic dystrophy can have 50 to 50,000 repeats, the more repeats an individual has the worse their symptoms are. The increased number of repeats produces an expanded version of mRNA, which then forms clumps inside the cell that interfere with the production of many other proteins. These clumps prevent muscle cells and cells in other tissues from functioning

Muscular dystrophy (MD) is a group of genetically transmitted diseases characterized by progressive symmetric wasting of skeletal muscles without evidence of neurologic involvement (Lewis, 2011). There are four different types of muscular dystrophy. The four types are Duchenne, Becker, Landouzy-Dejerine, and Erb. Duchenne muscular dystrophy is the most common type among children. It only affects boys; it’s passed down from the mother. Duchenne muscular dystrophy is created from X-linked recessive gene from the mother. About one in thirty-five hundred boys are born with Duchenne muscular dystrophy. The boys will experience weakening of the muscles, wasting and contractures and inability to walk by themselves by the time they even reach

Family history is a big part in diagnosing a person with (DMD) since it’s a genetic disease. Patients with a family history of (DMD) can get a screening including fetuses in the womb. Genetic testing for these conditions in future pregnancies of an affected individual or parents of an affected individual can be done before birth through amniocentesis or chorionic villus sampling (Quercia). Amniocentesis is when doctors take fluid from the amniotic sack and test it for and chromosomal abnormalities. (The main trait that causes (MD) is the protein dystrophin. Women pass on the genetic disease and are the carriers. Women that are carriers of (DMD) can have mild symptoms but won't be affected as a much as a male would since females have an unaltered X chromosome. The most common mechanisms of mutation are deletions and duplications largely clustered in the “hot spot,” a DNA sequence associated with an abnormally high frequency of mutation or recombination (MD). The dystrophin gene defect is affecting males in two out of three cases due to the X-linked inheritance (MD). One third of the cases of the gene defect is due to the defect happening as a result of a mutation in the germ cells of parents (MD). Scientists also believe that since the mother is the carrier of (DMD) that the egg cell has a dystrophin gene

Muscular dystrophy is a combination of diseases passed down through genes identified by progressive degeneration of the skeletal or voluntary muscles.(Alicia Foose,PhD, Patricia Ardovino,PhD,2008, p.141). This occurs due to mixture of hypertrophy, atrophy, and necrosis muscle cells. The muscle fibers increase in muscle size and results in muscle weakness while the muscle undergoes necrosis, fat and connective tissue replace the muscle fibers.(Sheila Grossman, Carol Mattson Porth,p.461).There are nine types of muscular dystrophy according to Alicia Foose, and Patricia Ardovino“Duchenne, Becker, Emery-Dreifuss, Limb-girdle, facioscapulohumeral, myotonic, oculopharyngeal distal, and congenital.”Each disease

There are five main type of CMT: CMT1, CMT2, CMT3, CMT4, and CMTX. Each type is caused by a different mutation in the genes, and each type has multiple subtypes. CMT1 is the most common type of CMT, accounting for about two-thirds of all cases. CMT1A, the most common CMT1 subtype, is caused by a mutation in the PMP22 gene on chromosome 17, and CMTIB is caused by a change in the MPZ gene on chromosome 1; both lead to problems with the myelin sheath on nerves (Kedlaya). The more rare subtypes of CMT1 are CMT1C, CMT1D, CMT1E, and CMT1F. Moreover, CMT2, which causes direct damage to the nerve axon, is the second most common type of CMT, with CMT2A, the most common subtype, caused by a mutation in the MFN2 gene (Muscular Dystrophy Association). CMT4 is also caused by a defect in the myelin sheath, and a famous subtype of CMT4 is Dejerine-Sottas Disease, a very severe form of CMT. Lastly, CMTX is is caused by a mutation of connexin 32 of the X-chromosome (Kedlaya). Because females have two X-chromosomes, CMTX most often occurs in women. Overall, CMT is caused by mutations in over 80 different genes, depending on the type and

For example, gene 3p22 would be located on chromosome 2, P-arm, and the 22nd region of the dark/light bands on the P-arm. Mutations on genes GNPTAB (12q23.2), GNPTG (16p13.3), and NAGPA (16p13.3) may cause about 10 percent of cases of stuttering. These three genes are involved in the breakdown and recycling of cellular components in the brain. In addition to the previously mentioned genes, DRD2 (11q23.2) and AP4E1 (15q21.2) may also contribute to stuttering behaviors. A DRD2 mutation causes myoclonus dystonia, which is relative to Tourette Syndrome—individuals with Tourette Syndrome exhibit many stuttering-like behaviors. Additionally, AP4E1disruption may be associated with Cerebral Palsy—individuals with congenital disorders like Cerebral Palsy have higher degrees of stuttering than individuals without congenital