Health Concerns

Muscular Dystrophy

The Various Types of Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD)

Mutations in a gene called dystrophin are responsible for the most common form of muscular dystrophy—Duchenne muscular dystrophy (Briguet 2008; Wang 2009; Muir 2009; Pilgram 2010). The dystrophin protein is responsible for maintaining muscle strength, so when the dystrophin gene is mutated in a way that prevents the dystrophin protein from being produced or functioning normally, muscles become weak (CDC 2012).

DMD occurs more frequently in young males, and accounts for approximately half of all muscular dystrophies (CDC 2012; Mayo Clinic 2012). In DMD, muscle weakness typically starts in the pelvis and legs, but can also occur in the arms, neck, and other regions of the body (PubMed Health 2013), while muscles of the face are normally spared. Calf muscles are also enlarged due to an accumulation of fatty tissue (NINDS 2011). People with DMD usually lose their ability to walk sometime between 7 and 13 years of age (CDC 2012), and they often die of respiratory failure before reaching age 40 as a result of damage to muscles that control breathing. About two-thirds of DMD cases run in families and one-third are caused by spontaneous mutations (NINDS 2011).

Females who carry the mutation usually do not display any symptoms, but about 8–10% of them will show some manifestation of the disease. When these symptoms do occur, they are typically more minor than the severe muscle weakness seen in males (Bushby 2005).

Signs and symptoms usually become evident when the child starts walking and may include (NINDS 2011; CDC 2012; Mayo Clinic 2012):

  • Clumsiness and falling more often than other children of the same age
  • A delay in walking
  • Difficulty getting up from the sitting or lying position
  • Difficulty running and jumping
  • Walking on tip toes
  • Large calf muscles
  • A waddling gait
  • A delay in using language
  • Learning disabilities

Approximately 90% of patients with DMD die from cardiomyopathy (a chronic heart disease in which the heart muscle is thickened, abnormally enlarged, or stiffened) or muscular respiratory failure (Finsterer 2006). Endocrine (hormonal) problems also appear in DMD (as well as some other muscular dystrophies), and the glucocorticoid medications frequently used for treatment can have additional adverse effects on the hormonal system (Ashizawa 2011). Furthermore, some studies have reported that DMD patients have problems with blood clotting, which can complicate surgery (Morrison 2011).

Becker muscular dystrophy (BMD)

Becker muscular dystrophy (BMD) is also caused by mutations to the dystrophin gene. Together, DMD and BMD are collectively known as “dystrophinopathies,” since they both arise as a consequence of dystrophin mutations.

While similar to DMD, BMD has significantly milder symptoms (Mayo Clinic 2012). These differences are attributed to the type of mutation that arises in the dystrophin gene. If the dystrophin gene is mutated in a way that leads to very little or no dystrophin protein, then the patient has more severe symptoms and is diagnosed with DMD. However, if the gene is mutated in a way that simply lowers the production of dystrophin protein, then the effect is less severe and those people are diagnosed with BMD (CDC 2012).

The incidence of BMD is approximately one-tenth that of DMD (Finsterer 2008; CDC 2012). Clinical disease also starts later, from as young as age 11 to as late as age 25, and patients typically live into middle age or later (NINDS 2011; Mayo Clinic 2012). In BMD, cardiac involvement usually starts later, in the third decade of life.

Myotonic dystrophy (DM)

Myotonic dystrophy (DM) usually has a late onset, between ages 20 and 30, and has a slowly progressive course. Thus, patients typically live longer than those with more severe forms of muscular dystrophy (Schara 2006; NINDS 2011). Two forms of DM are described (DM1 and DM2), and they share certain features, though they are caused by two different genetic mutations (DMPK for DM1 and CNBP for DM2). DM2 is usually less severe than DM1 (NHGRI 2012). About 1 in 8000 people are affected by DM worldwide, and DM1 is more common in most populations, although the frequency of DM1 and DM2 is similar in people from Germany (NIH Genetics Home Reference 2013A; NHGRI 2012). In the majority of populations, DM1 (also called Steinert’s disease) appears to be more common (NIH Genetics Home Reference 2013A). DM1 is also the most common form of adult-onset muscular dystrophy (NINDS 2011; Romeo 2012). DM1 affects both men and women and typically becomes more severe with progressive generations, a phenomenon known as “anticipation” (Ekström 2010; NINDS 2011; Romeo 2012; Sahenk 2011).

A genetic diagnosis for DM became available in 1992 after researchers came to understand that both DM1 and DM2 are caused by a genetic phenomenon called a “triplet repeat.” For this type of mutation, a certain 3 “letter” section of the genetic code is erroneously repeated many times (eg, CTG-CTG-CTG-CTG…); the more times the triplet is repeated, the greater the likelihood of disease occurrence and severity (Brook 1992; NINDS 2011). An interesting finding in DM1 is that the levels of serum coenzyme Q10 (CoQ10) are significantly and inversely related to the degree of the triplet repeat expansion; in other words, lower CoQ10 levels are associated with a greater number of triplet repeats (Siciliano 2001).

Myotonia—the inability to quickly relax muscles after a sudden contraction—is characteristic of DM (NINDS 2011). Cataracts and retinal or corneal changes are a few of the main eye problems in patients with DM1. Heartburn, regurgitation, bloating, and abdominal pain are some gastrointestinal complaints that have been reported (Ekström 2010; Ashizawa 2011).

Distal Muscle Dystrophy

Distal muscle dystrophy refers to a group of at least six muscle diseases that affect both males and females, usually between the ages of 40 and 60. As the name implies, distal muscle dystrophy affects distal muscle groups, which are muscle groups located furthest from the core of the body (eg, forearms, hands, lower legs, and feet). Often, diseases in this group affect fewer muscles, are less severe, and progress more slowly than other forms of MD (NINDS 2011). Although the molecular genetics of the various types of distal muscular dystrophy are still being delineated, mutations in the dysferlin gene, which codes for a protein of the same name thought to be involved in muscle repair, have been implicated (Kawai 2011).

Congenital Muscular Dystrophies (CMDs)

Congenital muscular dystrophies (CMDs) include a group of conditions that vary in severity and age of onset. Over 10 genes have been implicated in the formation of various congenital muscular dystrophies (Sparks 2011; Mercuri 2012).

In patients with CMD, muscle weakness and muscle tissue abnormalities are present from birth or before age 2 (Mayo Clinic 2012). Some CMD patients show normal intellectual development, while others have severely impaired cognition (NINDS 2011). It is anticipated that with developments in genetic technologies it will soon be easier to identify the different forms of CMD (Mercuri 2012).

Limb-girdle Muscular Dystrophy (LGMD)

Limb-girdle muscular dystrophy (LGMD) was, for many years, diagnosed based on the exclusion of other dystrophies. In recent years, however, several genetically-distinct subtypes have been discovered and over 12 forms can now be specifically identified. This group includes muscular dystrophies characterized by weakness, wasting, and impaired reflexes in proximal muscles, or muscles closest to the core of the body (eg, shoulder and hip reflexes) (Rocha 2010; NINDS 2011), while facial muscles are generally spared. In addition, intelligence is unaffected, and cardiomyopathy occurs in some LGMD patients (NINDS 2011).

Emery-Dreifuss Muscular Dystrophy

Emery-Dreifuss muscular dystrophy is another progressive neuromuscular degenerative disease. Three genes have been associated with this condition (Walter 2007; Bonne 2010). It is characterized by the triad of early-onset contractures (which describe an abnormal shortening of tissue at joints including the elbows and ankles), slowly progressive muscle weakness, and cardiac involvement (Ellis 2006; Bonne 2010; NINDS 2011).

Almost all patients have to use pacemakers for their heart problems by the age of 30, and females can develop heart problems without having any signs of muscle weakness (NINDS 2011). Furthermore, the involvement of respiratory muscles may cause respiratory difficulties and respiratory failure (Simonds 2002), with pneumonia as a possible complication (Amato 2011).

Fascioscapulohumeral Muscular Dystrophy (FSHD)

Fascioscapulohumeral muscular dystrophy (FSHD) affects approximately 1 in 20 000 individuals worldwide (Tawil 2008; Scionti 2012). As the name suggests, it leads to a progressive weakness in the muscles of the face (generally being more severe for the lower muscles of the face), shoulders, and upper arms. Muscles of the eyes and mouth are often the first ones affected (NINDS 2011). As a result, patients often cannot close their eyes completely and are unable to smile, which gives them a flat affect (Sahenk 2011; NINDS 2011). Muscles of the lower shoulders, chest, and abdomen may also be affected (NINDS 2011), and one of the earliest telltale signs of this disease is the inability to reach above shoulder level, due to the weakness of the muscles that stabilize the shoulder blade (Tawil 2008).

Extramuscular involvement includes high-frequency hearing loss that usually starts in early infancy (NIH 2011), irregularities in the capillaries of the eyes (Paunescu 2006), and an abnormal heart rhythm (Tawil 2008).

Oculopharyngeal Muscular Dystrophy (OPMD)

Oculopharyngeal muscular dystrophy (OPMD) includes conditions that affect both males and females and do not appear until the fourth or fifth decade of life. This type of muscular dystrophy is distributed worldwide. In the United States, it mostly affects people of French-Canadian descent and Hispanic individuals from northern New Mexico. The earliest symptom of OPMD is ptosis (or drooping eyelids), which affects both eyes, but asymmetrically. This symptom is sometimes so severe that people have to compensate by tilting back their head and raising their eyebrows (Abu-Baker 2007; NINDS 2011). Additional weakness in the facial and pharyngeal muscles often makes swallowing difficult. Initially, this is apparent for solid foods but, as the disease progresses, it also occurs for liquids (Abu-Baker 2007; NIH Genetics Home Reference 2013B).