Limb-girdle muscular dystrophies include at least 18 different inherited disorders, which first affect the muscles around the shoulder girdle and hips. These diseases get worse, and may eventually involve other muscles.

Muscular dystrophy - limb-girdle type (LGMD)

Limb-girdle muscular dystrophies are a large group of genetic diseases in which there is muscle weakness and wasting (muscular dystrophy).

In most cases, both parents must pass on the non-working (defective) gene for a child to have the disease (autosomal recessive disorder). However, in some rare types only one parent needs to pass on the bad gene to affect the child (autosomal dominant disorder). For some of these conditions, the defective gene has been discovered. For others, the gene is not yet known.

An important risk factor is having a family member with muscular dystrophy.

Typically, the first sign is pelvic muscle weakness (difficulty standing from a sitting position without using the arms, difficulty climbing stairs). The weakness starts in childhood to young adulthood.

Other symptoms include:

• Abnormal, sometimes waddling, walk
• Joints that are fixed in a contracted position (late in the disease)
• Large and muscular-looking calves (pseudohypertrophy), which are not actually strong
• Loss of muscle mass, thinning of certain body parts
• Low back pain
• Palpitations or passing-out spells
• Shoulder weakness
• Weakness of the muscles in the face (later in the disease)
• Weakness in the muscles of the lower legs, feet, lower arms, and hands (later in the disease)

• Blood creatine kinase levels
• DNA testing
• Echocardiogramor ECG
• Electromyogram(EMG) testing
• Muscle biopsy

There are no known treatments that directly reverse the muscle weakness. Gene therapy may become available in the future. Supportive treatment can decrease the complications of the disease.

Management is tailored to the patient and his or her symptoms. It includes:

• Heart monitoring
• Mobility aids
• Physical therapy
• Respiratory care
• Weight control

Surgery is occasionally needed.

The Muscular Dystrophy Association is an excellent resource (800-572-1717).

In general, people tend to have weakness that slowly gets worse in affected muscles and spreads.

The disease causes significant loss of mobility or dependence on a wheelchair within 20 - 30 years.

Heart muscle weakness and abnormal electrical activity of the heart can increase the risk of palpitations, fainting, and sudden death. Most patients with this group of diseases live into adulthood, but do not reach their full life expectancy.

• Abnormal heart rhythms
• Contractures of the joints
• Difficulties with activities of daily living due to shoulder weakness
• Progressive weakness, which may lead to needing a wheelchair

Call your health care provider if you or your child feel weak while rising from a squatting position. Call a geneticist if you or a family member has been diagnosed with muscular dystrophy and you are planning a pregnancy.

Genetic counseling may guide some families about their risks and help with family planning.

Some of the complications can be prevented with appropriate treatment. For example, a cardiac pacemaker or defibrillator can significantly reduce the risk of sudden death due to an abnormal heart rhythm. Physical therapy may be able to prevent or delay contractures and improve quality of life.

Affected people may want to do DNA banking. DNA testing is recommended for those who are affected, in order to identify the family gene mutation. Once the mutation is found, prenatal DNA testing, testing for carriers, and preimplantation genetic diagnosis are possible.

Duchenne muscular dystrophy is an inherited disorder that involves rapidly worsening muscle weakness.

Pseudohypertrophic muscular dystrophy; Muscular dystrophy - Duchenne type

Duchenne muscular dystrophy is a rapidly-worsening form of muscular dystrophy. Other muscular dystrophies (including Becker's muscular dystrophy) get worse much more slowly.

Duchenne muscular dystrophy is caused by a defective gene for dystrophin (a protein in the muscles). However, it often occurs in people without a known family history of the condition.

Because of the way the disease is inherited, males are more likely to develop symptoms than are women. The sons of females who are carriers of the disease (women with a defective gene but no symptoms themselves) each have a 50% chance of having the disease. The daughters each have a 50% chance of being carriers.

Duchenne muscular dystrophy occurs in approximately 1 out of every 3,600 male infants. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy.

Symptoms usually appear before age 6 and may appear as early as infancy. They may include:

• Fatigue
• Mental retardation (possible, but does not worsen over time)
• Muscle weakness
  • Begins in the legs and pelvis, but also occurs less severely in the arms, neck, and other areas of the body
  • Difficulty with motor skills (running, hopping, jumping)
  • Frequent falls
  • Rapidly worsening weakness
• Progressive difficulty walking
  • Ability to walk may be lost by age 12

By age 10, the person may need braces for walking. By age 12, most patients are confined to a wheelchair.

A complete nervous system (neurological), heart, lung, and muscle exam may show:

• Abnormal heart muscle (cardiomyopathy)
• Congestive heart failure or irregular heart rhythm (arrhythmias) -- rare
• Deformities of the chest and back (scoliosis)
• Enlarged calf muscles, which are eventually replaced by fat and connective tissue (pseudohypertrophy)
• Loss of muscle mass (wasting)
• Muscle contractures in the heels, legs
• Muscle deformities
• Respiratory disorders, including pneumonia and aspiration of food or fluid into the lungs (in late stages of the disease)

Tests may include:

• Electromyography (EMG)
• Genetic tests
• Muscle biopsy
• Serum CPK

There is no known cure for Duchenne muscular dystrophy. Treatment aims to control symptoms to maximize quality of life. Gene therapy may become available in the future.

Activity is encouraged. Inactivity (such as bedrest) can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength and function. Orthopedic appliances (such as braces and wheelchairs) may improve mobility and the ability to care for yourself.

You can ease the stress of illness by joining a support group where members share common experiences and problems. See muscular dystrophy - support group. The Muscular Dystrophy Association is an excellent source of information on this disease.

Duchenne muscular dystrophy leads to quickly worsening disability. Death usually occurs by age 25, typically from lung disorders.

• Cardiomyopathy
• Congestive heart failure (rare)
• Deformities
• Heart arrhythmias (rare)
• Mental impairment (varies, usually minimal)
• Permanent, progressive disability
  • Decreased mobility
  • Decreased ability to care for self
• Pneumonia or other respiratory infections
• Respiratory failure

Call your health care provider if:

• Your child has symptoms of Duchenne muscular dystrophy
• Symptoms worsen, or new symptoms develop, particularly fever with cough or breathing difficulties

Genetic counseling is advised if there is a family history of the disorder. Duchenne muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy.

Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Muscular dystrophies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa:Saunders Elsevier; 2007:chap 608.

Duchenne muscular dystrophy (DMD) is a severe recessive X-linked form of muscular dystrophy characterized by rapid progression of muscle degeneration, eventually leading to loss of ambulation and death. This affliction affects one in 3500 males, making it the most prevalent of muscular dystrophies.

Duchenne Muscular Dystrophy is an X chromosome-linked, inherited, progressive, muscle wasting disease, which affects approximately one out of 3,500 male children.

For explaining the nature of Duchenne Muscular Dystrophy (DMD), we might start with the chromosomes.

Chromosomes are specifically folded DNA molecules. We speak of chromosomes rather than DNA, because in this form the DNA molecules are visible under the microscope, therefore, distinguishable from each other.

In normal circumstances we have 46 nuclear chromosomes. In certain conditions, such as cancer (for example in cancerous 'HeLa cells'), the number of chromosomes could be different. The 46 chromosomes include 2 sex chromosomes as well. We inherit 23 nuclear chromosomes (22 plus 1 sex chromosome) from each of our parent.

Females have two X chromosomes (XX), males have one X and one Y (XY). They each contribute one to their child. Since the mother has two X-es, she passes down one X, therefore the father's chromosomes decides the child's sex.

Duchenne muscular dystrophy arises from the mother's defective sex chromosome. The disease is a recessive trait, meaning only one of the mothers' two XX sex chromosomes is defective and the other X chromosome is able to compensate.

For this reason, if she passes the disease-carrying chromosome to her daughter, the daughter's disease-free paternal X chromosome would compensate. The girl will carry, and potentially be able to pass, the faulty chromosome to her child/children, but, she, herself, will not be at all, or just mildly, affected.

If, however, her son gets the disease-carrying chromosome, he will not have that opportunity; due to his Y chromosome from his father, he cannot compensate. Unfortunately, he will get the full-blown disease.

While the majority of the disease are inherited from the mother, as detailed above, 'spontaneous mutations', when the damage to the gene happens in the male child, is also possible.

So, what is the role of the X chromosome in that disease?

The long DNA molecules, therefore their tightly packed forms, the chromosomes, have specific areas, called 'genes'. Every chromosome has its 'own' specific genes on their 'own' specific areas. Those genes have the 'blueprints', the instructions, for the body to build proteins. Proteins are compounds, specific substances, which are essential to life; they are vital for every function, feature, and aspects of the body.

If a gene is faulty, inherited from either or both parents, (Duchenne muscular dystrophy is inherited only from the mother), or damaged/changed by environmental factors (like radiation, chemicals, or others), also by life style (smoking for example), then it cannot provide a correct instruction to assemble a properly working protein.

The fault arise from mistakes in the instruction; some parts are missing, others are repeated, and some are changed. It is like someone is building a cupboard. If the instruction gives the wrong dimensions for some parts or even omit some others parts, then it would be impossible to build a proper cupboard.

Neither can the body assemble the protein, called 'dystrophin', from the improper instruction given by the defective Dystrophin gene of the X-chromosome.

Dystrophin is a muscle protein with mechanical and protective functions. It might involve in cell to cell communications, as well. Due to the lack of dystrophin protein the muscles became weaker, damage easily, and gradually break down, waste away.

Symptoms (difficulty in sitting unaided, delayed start for walking, frequent stumbling and falling, difficulty in getting up, for example), could start to appear as early as one year of age, and the disease quickly progresses to the stage when the child needs a wheelchair (around 8-12 years of age).

Since the disease weakens not only the skeletal muscles, but all muscles, heart rhythm and the pumping ability of the heart are also affected. Likewise, breathing becomes difficult and needs assistance as the disease progresses to those involved muscles.

Lifespan, unfortunately, is not expected to extend beyond 30 years. Cure is not possible at the present.

Treatments are aimed to delay the wastage, steroid medication (with Vitamin D and calcium supplement to counteract its possible bone weakening side-effect), physiotherapy, and water exercises, possibility of low frequency electrical muscle stimulation, among others.

Improving the quality of the patients' life includes corrective bone surgery (bone deformities occurs frequently) to improve posture and comfort, braces, use of wheelchair (manual then electric), heart medications/treatments, assistance with breathing (ventilator, masks, others), - education/information/help to parents and carers, for example.

Research is ongoing, internationally, on several possible aspects; a few examples are:

· 'Gene bandage', specifically designed for the protein assembling process to 'skip over' the faulty segment of the gene, enabling the production of dystrophin,

· Implantation of stem cells,

· 'utrophin-based therapy', Utrophin is another muscle protein with similar function. Research going on to use it for compensate for the lack of dystrophin,

· Researching a drug (recently trialled in Diabetes Type 2 research, as well), which, also, could increase the level of HSP72 (a specific protein). HSP72 expected to improve muscle function, decrease muscle break down, and increase lifespan by 20 %,

· and an older research into low frequency electrical muscle stimulation.