Muscular Dystrophy

I'm Grateful I've Proved Them Wrong

Todd T. Eckdahl

• Publisher: Momentum Press
• Year: 2018
• ISBN:
  9781944749682
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

This book presents muscular dystrophy (MD) as a group of genetic diseases with a worldwide occurrence of about 1 in 3, 500 births that causes muscle wasting and weakening.

It describes Duchenne MD as the most common type of MD, almost exclusively affecting males at a rate of about 1 in 5, 000 boys, and eight rarer types of MD that are categorized by age of onset, muscles affected, disease progression, severity of symptoms, and health complications. The author describes how physical examination, muscle biopsy, medical imaging, and genetic testing is used to diagnose MD He further explains the underlying causes of the various types of MD as mutations in genes that encode proteins needed for the development, function, maintenance, and replacement of muscle cells and illustrates patterns by which they are inherited.

There is no treatment that can reverse the progressive deterioration of muscles caused by MD, but the book offers insight into drug treatments and physical therapies that help maintain muscle strength and reduce health complications. It concludes with explanations of promising new ways to treat or perhaps cure MD, including experimental drugs, stem cell therapy, and gene therapy.

CHAPTER 1

Symptoms and Diagnosis

MD is a group of diseases characterized by progressive weakening and wasting of muscles. Nine types of MD are commonly recognized that vary in the age of onset, muscles affected, progression of myopathy, severities of symptoms, and health complications (Table 1.1). The age of onset of MD types ranges widely. Some types of MD cause symptoms at birth, whereas others cause symptoms in infancy, early childhood, adolescence, or adulthood. Some types affect muscles lying near the center of the body, whereas others affect muscles in the extremities. A subset of MD diseases causes deterioration of the larger muscles of the trunk and legs, but others affect the smaller muscles of the face or throat. Life-threatening effects on heart muscle are associated with some types of MD, but not others. The symptoms and health complications caused by most types of MD lower life expectancy, but a few types do not.

Table 1.1 The nine most common types of MD

Symptoms of Muscular Dystrophies

Duchenne muscular dystrophy (DMD) is the most common type of MD, and it affects males almost exclusively, at a rate of about 1 in 5,000 boys. The rate is expressed in Table 1.1 as 20 in 100,000 for easy comparison to other types of MD. The symptoms of DMD appear at the age of 2 to 5 years and result from effects on muscles in the hips, thighs, and calves. An early sign of DMD is pseudohypertrophy of the leg muscles, especially those in the calves, which means that they appear to have been enlarged by becoming stronger but are actually enlarged by the abnormal accumulation of scar tissue within the muscles. Compared to typically developing children, toddlers with DMD have more trouble getting up from the floor, and often grasp their legs to push themselves to an upright position, which is known as Gower’s sign. They also have difficultly learning to walk, and when they do, they develop an unusual gait, swaying from side to side, planting their feet unevenly, and keeping their balance by sticking their bellies out while pulling back their shoulders. Although they learn to use their legs to jump, climb stairs, and run, they display a lack of coordination when doing so. The progressive deterioration of leg muscles causes children with DMD to fall with increasing frequency and gradually eliminates their ability to walk, which is called ambulation. Most of these boys require the use of a wheelchair by the age of 7 to 12 years. As the effect of their disease spreads to shoulder muscles, children with DMD at first have trouble raising their arms above their heads, and in their teenage years, gradually lose arm strength and coordination. Children with DMD also develop muscle contractures, which are permanent shortenings of muscles that prevent their limbs from functioning. The life expectancy of people with DMD is reduced by health complications associated with the deterioration of heart muscle and muscles used for breathing. The average life expectancy of DMD patients is currently 27 years, but good health care enables some to survive 40 years or more. Other common health complications of DMD include intellectual disability, scoliosis, and eating problems.

Becker muscular dystrophy (BMD) is closely related to DMD because it results in similar symptoms and has a similar underlying genetic cause. The distinction between the two diseases is in their severity, age of onset, and rate of progression of symptoms and health complications. BMD is less common than DMD, with a rate of occurrence of about 1 in 25,000 boys. The first signs of BMD appear in late childhood or adolescence as weakness of muscles in the hips and thighs. As muscle weakness progresses and spreads to the calves, pseudohypertrophy often follows. The extent to which these children can run, climb stairs, walk, and stand upright varies widely. Some maintain most or all of their ability to walk, whereas others require assistive devices, such as a wheelchair. Upper-body muscles are not as severely affected, but effects on shoulder muscles can limit arm strength and range of motion. The degree to which BMD leads to heart disease varies, and there is a positive correlation between early onset and the development of heart problems. Respiratory problems such as restricted breathing and recurrent lung infections sometimes occur for patients with BMD due to weakening of muscles needed for breathing and coughing. Although the life expectancy for people with BMD correlates with their access to good health care, most survive to the age of 40 or 50 years.

The second most common type of MD, occurring in about 1 in 9,000 people, is myotonic dystrophy (DM). The name of the disease comes from myotonia, which is the inability to relax voluntary muscles after they have been contracted. Myotonic dystrophy is often abbreviated as DM, for its Greek name, dystrophia myotonica. DM occurs as two types, referred to as DM1 and DM2, both characterized by progressive weakening and wasting of muscles in the hands, face, neck, arms, hips, and calves, and eventually of muscles needed for the function of the heart, lungs, and other organs. The symptoms of DM2 are not as severe as those of DM1, and DM2 is less common than DM1. The onset of symptoms for DM2 is always in adulthood, whereas DM1 symptoms can appear at any age from infancy to adulthood. The first muscles to be affected by DM2 are hip muscles, and progressive weakening of them can cause ambulation problems. Later, weakness spreads to the muscles of the face and the extremities. For DM1, there is a positive correlation between the age of onset and the severity of symptoms. The earlier the onset, the more severe the symptoms become. Congenital DM1 (symptoms appearing at birth) is the most severe form and is associated with life-threatening symptoms caused by heart and respiratory problems. Infants with DM1 usually have physical and cognitive developmental delays. When DM1 appears in a child or an adolescent, cognitive and behavioral effects are more prevalent than physical ones. Muscles of the hand are most often affected in adult-onset DM1. A person with DM1 might find it difficult to ungrasp a pencil, loosen their grip on a baseball, or let go of a steering wheel. Health complications of adult-onset DM1 include cataracts, speech impairment, eating problems, recurrent respiratory infections, gastrointestinal problems, intellectual disability, daytime sleepiness, and diabetic symptoms. Males with DM1 usually have more severe symptoms than females with the same disease. The life expectancy for people with DM varies considerably. Many people with DM have a normal life expectancy, but congenital forms of DM can cause death in infancy or childhood.

Facioscapulohumeral muscular dystrophy (FSHD) is named for its effects on the muscles of the face (facio-), the shoulder blades (scapulo-), and the upper arms (humeral). FSHD occurs in about 1 in 25,000 people, and although its onset is usually in adolescence or adulthood, a rare form also occurs with onset in infancy. The two types of this disease, FSHD1 and FSHD2, have different genetic causes. The first muscles to be affected by both types are those of the face, shoulders, and arms, but muscle weakness will spread to the lower legs and the hips. The effects of FSHD are often unequal on one side of the body compared to the other. The severity of symptoms ranges widely, and they appear gradually over years. Some people develop leg muscle weakness that takes away their independent ambulation and requires them to use a wheelchair, but others only experience effects in their arms. Progressive weakening of shoulder muscles often leads to scapular winging, which means that the shoulder blades stick out from the back. Some people with FSHD only have weakness of the muscles surrounding their eyes or their mouths, and others have such mild symptoms that they are unaware of their disease. Health complication of FSHD include scoliosis, minor hearing loss, and vision problems. Most people with FSHD have a normal lifespan.

Congenital muscular dystrophy (CMD) refers to any of more than 30 genetic diseases that cause muscle weakness at birth or in infancy, followed by muscle wasting. CMD is caused by a small number of related molecular and cellular malfunctions. The collective occurrence of CMD has been estimated to be about 1 in 50,000 infants, but this estimate is expected to rise with increased awareness and improved diagnosis, especially genetic diagnosis. CMD causes hypotonia, also known as floppy baby syndrome, which is the occurrence of weak muscles throughout the body. Infants with hypotonia seem “floppy” because of their weak muscles and are often delayed in meeting developmental milestones such as rolling over, sitting up, crawling, and walking. For some infants, hypotonia in the mouth and throat makes it difficult for them to drink breast milk or formula, which leads to poor weight gain. The rate of progression and severity of muscle weakness and wasting varies among CMD types. In many cases, muscle function gradually worsens, but in others it stabilizes and sometimes improves. The most common muscles affected by CMD are those of the neck, arms, trunk, and legs. Common health complications of CMD include heart problems, respiratory disease, scoliosis, and eating problems. The life expectancy of people with CMD varies widely. Some CMD forms cause death in infancy or childhood, whereas others do not alter normal life expectancy.

Limb-girdle muscular dystrophy (LGMD) is a group of muscular diseases that have different genetic causes but which share effects on the muscles attached to the bones of the limb girdle, which includes the shoulder girdle and the pelvic girdle. LGMD causes weakening and wasting of the shoulder and hip muscles that are used to move the arms and the legs. These muscles are called proximal muscles because they are close to the midline of the body. Occurring in about 1 in 50,000 people, LGMD first presents itself at various ages from childhood to adulthood, progresses at varying rates, and varies widely in symptom severity. The early signs of hip muscle weakness caused by LGMD include swaying from side to side while walking, walking on the balls of the feet, having trouble climbing stairs, and having trouble standing up from a seated position. For some people with LGMD, these symptoms advance to the point where they lose independent ambulation and require a mobility aid, such as a wheelchair. Early signs of shoulder muscle weakness are difficulty raising the arms above the head, trouble lifting objects with outstretched arms, and problems with tasks that require arm extension, such as eating. Progressive weakening of shoulder muscles often leads to scapular winging. Sometimes LGMD affects other muscles, such as those of the hands, feet, and lower legs. LGMD can cause contractures of the muscles of the joints in the arms and legs, pseudohypertrophy of the calf muscles, and scoliosis. Although the most important health complications of LGMD are heart problem and respiratory problems, people with LGMD usually have a normal life expectancy.

Emery–Dreifuss muscular dystrophy (EDMD) occurs in about 1 in 100,000 people. Its onset is most often between childhood and adolescence, when muscles of the shoulders, upper arms, and lower legs begin to weaken. Early signs of the disease include walking on the toes, adopting an abnormal waddling gait, having trouble bending the arms or raising them above the head, and adopting an unusual gait. Joint deformities often develop from contractures, resulting in stiffness and limitations of arm and leg mobility. As EDMD progresses, its effects on leg muscles often worsen to the point where people are no longer able to walk without assistance, and sometimes lose independent ambulation. Weakening of the heart often occurs in adolescence or adulthood, which reduces the life expectancy for people with EDMD to between 40 and 60 years. Other health complications of EDMD include contractures and breathing problems.

Distal myopathy, also known as distal muscular dystrophy, is a general name for a group of genetic diseases that are characterized by progressive weakening and wasting of the distal muscles, which include the muscles of the lower arms, hands, calves, and feet. Distal myopathy is rare, occurring in about 1 in 100,000 people. The age of onset for distal myopathy types ranges from childhood to adulthood. Early symptoms include noticeable weakness of the ankles, which causes an unsteady gait, and weakness of the wrists and fingers, which limits dexterity and affects the ability to grasp objects. The progression of symptoms for different forms of distal myopathy varies, but most of them limit the range of motion of the arms and affect the ability to walk without assistance. Some forms of distal myopathy cause weakness of the vocal cords, causing the voice to be weak and breathy at first, and later to be hoarse and nasal. Some distal myopathy patients experience weakness in muscles of the throat, which results in eating problems. The most important health complications of distal myopathy are heart disease and respiratory problems. Other health complications might include speech problems, eating problems, and recurrent respiratory infections. People with distal myopathy usually have a normal life expectancy.

Oculopharyngeal muscular dystrophy (OPMD) occurs in about 1 in 100,000 people, and symptoms first appear in adulthood, typically at the age of 40 years or later. OPMD is named for its effects on the muscles that control the eyelids (oculo-), and the muscles of the throat (pharyngeal). The earliest sign of the disease is droopy eyelids. As the disease progresses, it affects muscles in the throat, which causes people to have trouble swallowing food at first, and trouble drinking liquids later. Weakening of the tongue frequently occurs, which adds to the eating difficulties and affects speech. In the later stages of OPMD, leg and hip muscles can be affected, requiring the use of a cane or a walker. Health complications of OPMD include weight loss from eating problems, and pneumonia from the pulmonary aspiration of food, liquids, or saliva into the lungs. The life expectancy for people with OPMD is normal.

The disease that Joe Akmakjian was born with, SMA type 2, is not considered to be a type of MD, but it is closely related. SMA type 2 is distinct from MD because the underlying cause is not weakening and loss of muscles, but loss of the nerve cells in the spinal cord and brain that control muscles. The name of the disease reflects the loss of nerves in the spine that leads to muscle atrophy. SMA type 2 is a neuromuscular disease that affects proximal muscles, such as those of the shoulders, upper arms, hips, and thighs. There are five types of SMA that can be distinguished by age of onset and severity of symptoms, and the overall occurrence of them is 1 in 10,000 births. The symptoms of SMA type 0 can be noticed in the later stages of pregnancy as an abnormally inactive fetus. Babies born with SMA type 0 cannot breathe or swallow on their own and usually die within 6 months. SMA type 1 is the most common form of SMA and causes muscle weakness, movement deficiencies, and feeding problems in infants. Severe respiratory problems cause most infants with SMA type 1 to die within 1 year. SMA type ...