Spinal Muscular Atrophy : An Incurable Autosomal Recessive Disease

Spinal Muscular Atrophy is classify as an interneuron abnormality and loss of the anterior horn cells in the spinal column. SMA is categorized into three subtypes with the classification embedded on the motor milestone achieved. Spinal type I (Werdnig-Hoffman disease) child is to weak that they never learn to sit, type II child learn to sit but never learn to walk without assistive device, and type III (Kugelberg-Welander disease) child can walk independently (Tecklin, 2015).

Muscular dystrophy (MD) is a rare, progressive disease relating to the weakening of skeletal muscles. There are more than 30 types of muscular dystrophy that are further divided into nine categories. Duchenne MD is the most common and acute form of this condition that accounts for 50% of all the cases. Duchenne MD (DMD) is most prevalent in males, between the ages of 3 and 5 (Norwood, FL, et al. 2009). This X-linked disease occurs for 1 in every 3,500 males, which results in confinement to a wheelchair (Blake et al., 2002). Becker MD (BMD) is a less severe type of this condition. A study conducted in the United Kingdom by Bushby, Thambyayah and Gardner-Medwin, the incidence of Becker MD was estimated to be 1 in 18,450 males at birth

Muscular dystrophy (MD) is a genetic disorder caused by incorrect or missing genetic information that leads to the gradual weakening of the muscle cells. Various causes lead to weak and deteriorating muscles depending on the type of muscular dystrophy the patient was affected by. However, there are many causes for muscular dystrophy due to the fact that there are thirty forms of muscular dystrophy, which are categorized under several categories. All are ultimately caused by autosomal recessive, autosomal dominant, sex-linked, and random mutations in very rare cases.

Prior to the 1980s, there was minimum knowledge relating to the causes of muscular dystrophy. However, in 1986, researchers discovered a gene, soon to be named dystrophin, on the X chromosome. The gene, when mutated, reacted by causing Duchenne muscular dystrophies. During 1987, the protein in relation to the gene discovered a year early was officially classified and named dystrophin. Duchenne Muscular Dystrophy (DMD) develops due to the mutated gene failure to supply active dystrophin. This minimum amount of dystrophin affects the body by developing muscle damage and continued weakness from early life.

What is Muscular Dystrophy, or MD for short. Muscular Dystrophy is a hereditary disease that effects the muscles which controls movement weaken overtime, and in some cases will affect the heart and other organs. Symptoms can show up in those as young as infants and can stay in those in the middle ages or older. There are nine major forms of MD including: Myotonic, Duchenne, Becker, Limb-girdle, Facioscapulohumeral, Congenital, Oculopharyngeal, Distal, Emery-Dreifuss. The form and severity vary by the age that MD occurs. Some types of MD will affect mostly males, while some people with MD will enjoy a slow progression with mild symptoms, but on the otherhand, others will experience swift and severe weakening, dying in their late teens and early 20’s. More than 50,000 Americans are affected by various types of MD.

Spinal muscular atrophy (SMA) is a generic, lethal condition characterized by an inability to will voluntary muscles as desired. The motor neurons responsible for exciting muscular contractions are deficient and loss of usage in voluntary muscles results in their atrophy. Characterized early in life, children with SMA exhibit difficulty in early voluntary muscular activities such as crawling, sucking, imitation of facial expressions, and breathing. Three stage of SMA exist: SMA I for children younger than six months, SMA II for children between 6-18 months of age, and SMA III for all remaining children.

The genetic disease known as Muscular Dystrophy first appeared in history in the year 1830. It was included in a written report by the Scottish Neurologist Sir Charles Bell. The disease soon became more prominent, where it appeared in several medical journals from the 1850’s and onwards. Several young boys were described as having a weakness which progressively worsened, along with problems walking. The disease led to their eventual premature deaths. A French Neurologist known as Guillaume Duchenne studied 13 boys who all had the most common and severe form of Muscular Dystrophy, soon to be known as Duchenne Muscular Dystrophy (NIH 2016). Muscular dystrophy refers to a group of more than 30 genetic diseases including Distal MD, Emery-Dreifuss MD, Facioscapulohumeral MD, Limb-girdle MD, Becker MD, Congenital MD, Myotonic MD and Oculopharyngeal MD. This review however will just focus on Duchenne muscular dystrophy.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder involving degeneration of anterior horn cells in the spinal cord due to a deficiency of SMN protein produced by the SMN1 gene. While this is an extensive topic, the following paper attempts to provide an overview of relevant aspects and treatment strategies of interest.

central nervous system disorders such as cerebral palsy and spinal cord injury (spina bifida); motor neuron disorders such as spinal muscular atrophy; peripheral nerve disorders such as Charcot-Marie-Tooth disease; neuromuscular junction disorders such as congenital myasthenia gravis; and muscle fiber disorders such as Duchenne's muscular dystrophy currently have no known definitive treatments or cures (p. 163).

Muscular dystrophy is a lethal sex-linked disorder characterised by progressive muscle weakness and muscle degeneration. It has been a medical problem for many years. In particularly Duchenne muscular dystrophy (DMD) for it is the most frequently occurring and one of the most rapidly progressive in children neuromuscular disorders (MDA, 2015). DMD affects approximately 1 in 3600 live male births throughout the whole world (MDA, 2015). DMD can cause or create an array of difficulties for diagnosed patients depending on how bad the patient’s case of DMD is. This is all as a result of the faulty or lack of the dystrophin gene, making it incredibly difficult for these patients to do simple activities like walking and running.

A muscular dystrophy is a group of diseases that is associated with progressive weakness and loss of an individual’s muscle mass. The condition causes the abnormal genes to interfere with the production of proteins needed to form healthy muscles. There is no medical cure for muscular dystrophy and related diseases, but strategies such as medication and therapy are used to manage the symptoms and slow the course of the disease. There are more than 30 types of muscular dystrophy, and the difference is based on the genes that cause it, the age when the symptoms appear first, how quickly the disease progresses and the muscles it affects (Tecklin, 2015).

Spinal Muscular Atrophy, also known as SMA, is the number one genetic disease killer of children under two years old. About one in every 6,000 babies are born with SMA and one in 40 people carry the gene that causes SMA. Spinal Muscular Atrophy is a genetic disease that affects the part of the nervous system that controls the muscle movement. Most of the nerve cells that control the muscles are located in the spinal cords. SMA is when there is a loss of nerve cells and protein in the spinal cord which is called motor neutrons. Motor neutron protein is necessary for muscles to function properly. This diseases weakens the muscles that affects an individual’s physical movement. Only few individuals with SMA are able to walk. This disease

Etiology - Amyotrophic lateral sclerosis is a disease that affects the nervous system. It affects the brain and the spinal cord and it controls the voluntary muscle movements and disables the body from being able to control movements such as speech, swallowing, and movement of the limbs. Unfortunately, there is no cure for Amyotrophic lateral sclerosis. There are two different kinds of amyotrophic lateral sclerosis, sporadic and familial. The sporadic type means that there is no specific cause for the disease. The familial type only affects about 5 to 10 percent of cases. This disease isn’t easily understood due to the severity of the disease. It is hard for many doctors to understand what causes this disease in most patients. Some things that could contribute to amyotrophic lateral sclerosis are: free radical damage, an immune response that targets motor neurons, imbalances in the chemical messenger glutamate, or a buildup of abnormal proteins inside nerve

ALS is named for its underlying pathophysiology, which is “amyotrophy” referring to the atrophy of muscles fibers, which denervated as their corresponding anterior horn cells degenerate. “Lateral sclerosis” refers to the changes seen in lateral columns of the spinal cord as upper motor neuron axons in these areas degenerate and are replaced by fibrous astrocytes. ALS affects motor neurons at two or more levels of the motor neuron network supplying multiple regions of the body and as a consequence, the communication between the neurons and muscle is lost, promoting progressive muscle weakening. That is, ALS affects lower motor neurons that reside in the anterior horn of the spinal cord and in the brain stem, corticospinal upper motor neuron

Figure 5: Phenotypes of mice with differing severity of SMA. a) Type 1 SMA hairless mice (left) alongside a wild-type mouse (right). b) Type 2 SMA causing paralysis of the hindlimbs (right) next to a WT mouse (left). c) Type 2 SMA causing the deformation of the back limbs (left) next to a control mouse (right). D) Type 3 mouse (top) with a shorter and fatter tail in comparison to a WT littermate (bottom) [Image: Hsieh-Li, H.M. et al., 2000].