what is the genetic cause of duchenne muscular dystrophy

Causes

Genotype-Phenotype correlation; Duchenne muscular dystrophy. Genotype: Dystrophin. 96% with frameshift mutation 30% with new mutation; 10% to 20% of new mutations are gonadal mosaic Clinical Weakness Onset age: 2 to 5 yrs Distribution. Proximal > Distal Symmetric Legs & Arms Most involved muscles: Adductor magnus in legs

Symptoms

The average life expectancy of people with muscular dystrophy depends on the form of the disease. Most patients with one of the nine forms of muscular dystrophy live into adulthood, reports WebMD. However, people with Duchenne muscular dystrophy live only into their 30s, although a few live until age 50.

Prevention

There are nine different types of MD:

• Myotonic: Most common MD in both men and women.
• Duchene: Most common in children from 2-6 years of age (life expectancy of 20 years).
• Becker: Symptoms tend to appear more slowly between 2-16 years old, but it can appear at age 20 (males may live to adulthood).
• Limb-girdle: Occurs in men and women from teenagers to adults. ...

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Complications

Heart and breathing problems also begin in the teen years and lead to serious, life threatening complications. DMD is caused by genetic changes ( DNA variants) in the DMD gene. DMD is inherited in an X-linked recessive pattern and may occur in people who do not have a family history of DMD.

What is the genotype for muscular dystrophy?

What is the life span of muscular dystrophy?

What are some interesting facts about muscular dystrophy?

Is DMD genetic?

What is the genetic cause of muscular dystrophy?

MD is caused by mutations (alterations) in the genes responsible for healthy muscle structure and function. The mutations mean that the cells that should maintain your muscles can no longer fulfil this role, leading to muscle weakness and progressive disability.

Is Duchenne muscular dystrophy a gene or chromosomal disorder?

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact. DMD is one of four conditions known as dystrophinopathies.

Why do boys get Duchenne muscular dystrophy?

DMD generally affects boys because the dystrophin gene is on the X chromosome. Chromosomes are the parts of your cells that contain your genes. Boys only have one X chromosome. Girls have two X chromosomes, one from each parent.

Which parent carries the muscular dystrophy gene?

Inheritance in DMD DMD is inherited in an X-linked pattern because the gene that can carry a DMD-causing mutation is on the X chromosome. Every boy inherits an X chromosome from his mother and a Y chromosome from his father, which is what makes him male.

Who is most likely to get Duchenne muscular dystrophy?

Due to the localization of the dystrophin gene on the X chromosome, DMD predominantly affects male children, while females are likely to be asymptomatic “healthy carriers” [2].

Can DMD be detected before birth?

Prenatal diagnosis. Genetic testing can also be used for prenatal diagnosis. This is when a baby is diagnosed with MD before birth using tests carried out during pregnancy. You may be offered these tests if you're pregnant and there's a possibility that your unborn baby has MD.

Can females have Duchenne muscular dystrophy?

Abstract. Duchenne muscular dystrophy usually affects males. However, females are also affected in rare instances. Approximately 8% of female Duchenne muscular dystrophy (DMD) carriers are manifesting carriers and have muscle weakness to some extent.

Can Duchenne muscular dystrophy be avoided?

Because DMD is a genetic disorder, you can't do much to prevent it. But if DMD runs in your family, you may consider talking with a genetic counselor and getting testing before having children.

Is muscular dystrophy a single gene disorder?

Both Duchenne and Becker muscular dystrophy are single gene disorders? caused by different mutations? in the DMD gene, which is located on the X chromosome?. They are both recessive? diseases, which means two copies of the mutated gene are needed for the disorders to occur.

What chromosome is muscular dystrophy found on?

DMD is a genetic disease caused by a gene on the X chromosome that mothers can pass on to their sons. The gene affects a protein called dystrophin that muscles require to function normally.

What type of mutation is DMD?

Dystrophinopathies are the most common forms of muscular dystrophy in childhood. They are caused by mutations in the X chromosome-linked DMD gene [OMIM: *300377] [1, 2]. DMD gene is the largest known human gene, spanning 2.22 Mb in the region Xp21, and it has 79 exons and 8 promoters.

What is mutations in genes?

Genetic mutations are changes to your DNA sequence that happen during cell division when your cells make copies of themselves. Your DNA tells your body how to form and function. Genetic mutations could lead to genetic conditions like cancer, or they could help humans better adapt to their environment over time.

What is the cause of muscular dystrophy?

Learn about MDA’s COVID-19 response Cause of DMD Until the 1980s, little was known about the cause of any of the forms of muscular dystrophy. In 1986, MDA-supported researchers identified a gene on the X chromosome that, when flawed (mutated), causes Duchenne, Becker, and an intermediate form of muscular dystrophies. Genes contain codes, or recipes, for proteins, which are important biological components in all forms of life. In 1987, the protein associated with the DMD gene was identified and named dystrophin. The dystrophin gene is the largest gene yet identified in humans and is located in the short arm of the X chromosome, in the Xp21.2 locus (a locus is the position of a gene on a chromosome). The majority of mutations of the dystrophin gene are deletions of one or more parts of it.1 DMD occurs because the mutated DMD gene fails to produce virtually any functional dystrophin. Individuals with BMD genetic mutations make dystrophin that is partially functional, which protects their muscles from degenerating as badly or as quickly as in DMD. The dystrophin protein transfers the force of muscle contraction from the inside of the muscle cell outward to the cell membrane. Because it connects the center of the muscle cell to the edge of the cell, the dystrophin protein is extremely long. One end is specialized for linking to the muscle cell interior and the other end is specialized for linking to a variety of proteins at the cell membrane. The long middle section, called the rod domain, is taken up by a series of repeating units called spectrin repeats. The repeated spectrin units in the middle of the protein play an important role in linking the two ends, but studies have shown that the exact number of these units is not critical for the function of the protein as a whole. Many cases of DMD are caused by mutations in the part of the gene that encodes this middle section. Production of the entire protein stops when the mutation is encountered. The absence of dystrophin sets in motion a cascade of harmful effects. Fibrous tissue begins to form in the muscle, and the body’s immune system increases inflammation. In addition to its force-transfer role, dystrophin provides the scaffold for holding numerous molecules in place near the cell membrane. Loss of dystrophin displaces these molecules, with consequent disruptions in their functions. Lack of dystrophin causes muscle damage and progressive weakness, beginning in early childhood. Inheritance in DMD DMD is inherited in an X-linked pattern because the gene that can carry a DMD-causing mutation is on the X chromosome. Every boy inherits an X chromosome from his mother and a Y chromosome from his father, which is what makes him male. Girls get two X chromosomes, one from each parent. Each son born to a woman with a dystrophin mutation on one of her two X chromosomes has a 50 percent chance of inheriting the flawed gene and having DMD. Each of her daughters has a 50 percent chance of inheriting the mutation and being a carrier. Carriers may not have any disease symptoms but can have a child with the mutation or the disease. DMD carriers are at risk for cardiomyopathy. Although DMD often runs in a family, it is possible for a family with no history of DMD to suddenly have a son with the disease. There are two possible explanations. The first is that the genetic mutation leading to DMD may have existed in the females of a family for some generations without anyone knowing. Perhaps no male children were born with the disease, or, even if a boy in an earlier generation was affected, relatives may not have known what disease he had. The second possibility is that a child with DMD has a new genetic mutation that arose in one of his mother’s egg cells. Because this mutation is not in the mother’s blood cells, it is impossible to detect by standard carrier testing. A man with DMD cannot pass the flawed gene to his sons because he gives a son a Y chromosome, not an X. But he will certainly pass it to his daughters, because each daughter inherits her father’s only X chromosome. They will then be carriers, and each of their sons will have a 50 percent chance of developing the disease and so on. A good way to find out more about the inheritance pattern in your family is to talk to your MDA Care Center physician or a genetic counselor. More information also is included in MDA’s booklet Facts About Genetics and Neuromuscular Diseases. Females and DMD Why don’t girls usually get DMD? When a girl inherits a flawed dystrophin gene from one parent, she usually also gets a healthy dystrophin gene from her other parent, giving her enough of the protein to protect her from the disease. Males who inherit the mutation get the disease because they have no second dystrophin gene to make up for the faulty one. Early in the embryonic development of a female, either the X chromosome from the mother (maternal X) or the one from the father (paternal X) is inactivated in each cell. Chromosomes become inactivated at random. In each cell, there is a 50 percent chance that either the maternal or paternal X chromosome will be inactivated, with the other left active. Usually, girls do not experience the full effects of DMD the way boys do, although they still have symptoms of muscle weakness. A minority of females with the mutation, called manifesting carriers, have some signs and symptoms of DMD. For these women, the dystrophin deficiency may result in weaker muscles in the back, legs, and arms that fatigue easily. Manifesting carriers may have heart problems, which can show up as shortness of breath or an inability to do moderate exercise. The heart problems, if untreated, can be quite serious, even life-threatening. In very rare instances, a girl may lack a second X chromosome entirely, or her second X may have sustained serious damage. In these cases, she makes little or no dystrophin (depending on the type of dystrophin mutation), and she develops a dystrophinopathy just as a boy would. A female relative of a boy with DMD can get a full range of diagnostic tests to determine her carrier status. If she is found to be a DMD carrier, regular strength evaluations and close cardiac monitoring can help her manage any symptoms that may arise. For more on DMD in females, see Debatable Destinies: Duchenne muscular dystrophy carriers carry on, despite uncertainty. References Hoffman, E. P., Brown, R. H. & Kunkel, L. M. Dystrophin: The protein product of the duchenne muscular dystrophy locus. Cell (1987). doi:10.1016/0092-8674(87)90579-4

Why do males get dystrophin?

Males who inherit the mutation get the disease because they have no second dystrophin gene to make up for the faulty one. Early in the embryonic development of a female, either the X chromosome from the mother (maternal X) or the one from the father (paternal X) is inactivated in each cell.

Why is DMD inherited in an X-linked pattern?

DMD is inherited in an X-linked pattern because the gene that can carry a DMD-causing mutation is on the X chromosome. Every boy inherits an X chromosome from his mother and a Y chromosome from his father, which is what makes him male. Girls get two X chromosomes, one from each parent.

What is the chance of a child with a dystrophin mutation inheriting a flawed gene?

Each son born to a woman with a dystrophin mutation on one of her two X chromosomes has a 50 percent chance of inheriting the flawed gene and having DMD. Each of her daughters has a 50 percent chance of inheriting the mutation and being a carrier.

Why does DMD occur?

DMD occurs because the mutated DMDgene fails to produce virtually any functional dystrophin. Individuals with BMD genetic mutations make dystrophin that is partially functional, which protects their muscles from degenerating as badly or as quickly as in DMD.

What causes DMD?

Many cases of DMD are caused by mutations in the part of the gene that encodes this middle section. Production of the entire protein stops when the mutation is encountered. The absence of dystrophin sets in motion a cascade of harmful effects.

What is the name of the protein that is associated with the DMD gene?

In 1987, the protein associated with the DMD gene was identified and named dystrophin.

What is the gene that causes Duchenne?

Many of the genetic mutations that cause Duchenne occur in the region of the gene responsible for dystrophin (called the DMD gene) that controls the middle of the protein, with the repeating spectrin units. But instead of just affecting the middle of the dystrophin molecule, these mutations usually stop the protein from being built any further, resulting in a much shorter, dysfunctional protein.

What are the two types of mutations that cause Duchenne?

Deletions and duplications are two kinds of mutations that can cause Duchenne, with long stretches of DNA called exons — which contain tens of thousands to millions of nucleotides — either left out or repeated when a cell divides. About 60 to 70 percent of mutations that cause Duchenne are deletions, according to Nelson.

What is the function of dystrophin in muscle cells?

In normal muscle cells, dystrophin transfers the force of muscle contractions from the inside toward the outside of the cell. “Dystrophin is the shock absorber that helps mitigate any damage in the muscle when muscle cells contract,” explains Barry Byrne, MD, PhD, the director of the Powell Gene Therapy Center at the University of Florida in Gainesville and the chief medical adviser of the Muscular Dystrophy Association. “Without it, muscles are damaged, there’s inflammation, and those muscles ultimately deteriorate.”

What is the role of dystrophin in muscle contractions?

Dystrophin acts as a shock absorber within the muscle cells, reducing any damage caused by muscle contractions. Shutterstock. Duchenne muscular dystrophy, a genetic disease characterized by progressive muscle weakness, is present at birth in people who have the condition. In people with Duchenne, the muscles lack a protein called dystrophin, ...

What is the middle of a dystrophin molecule?

The middle of the dystrophin molecule consists of a long series of repeated units , known as spectrin units. Research suggests that it’s not critically important for the entire length of spectrin units to be present for the dystrophin protein to be somewhat functional — instead, the molecule simply needs to be not a great deal shorter, and it needs to look normal at both ends.

What happens if you have different mutations on the same gene?

Different kinds of mutations on the same gene can all lead to a lack of dystrophin, a protein that’s critical for long-term muscle function.

Why does Duchenne have a dysfunctional protein?

But no matter the type of mutation, in Duchenne, it results in a dysfunctional protein — usually because it causes a premature stop codon, cutting the molecule short. “The end result is always the same,” says Nelson. “No dystrophin.”.

What causes DMD?

Most cases of DMD are caused when large pieces of the dystrophin gene are lost or deleted (‘deletions’). Less often, large pieces of the dystrophin gene are copied or duplicated (‘duplications’). DMD can also be caused by smaller changes in the DNA code. 4,5

What mutation codes for dystrophin?

The mutation in the gene that codes for dystrophin can be either: 6,7

When a baby grows up, can they pass the faulty dystrophin gene on to the next generation?

When the baby grows up, they can pass the faulty dystrophin gene on to the next generation. 6,7

Which gene is the largest?

The dystrophin gene is the largest known human gene, which means that it is at more risk of spontaneous mutations than smaller genes. 1

What is Duchenne muscular dystrophy?

Duchenne muscular dystrophy ( DMD) affects the muscles, leading to muscle wasting that gets worse over time. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and loss (atrophy) of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, ...

How is Duchenne muscular dystrophy diagnosed?

Duchenne muscular dystrophy (DMD) is diagnosed in young boys based on clinical examination, signs and symptoms, family history, and may be confirmed by the results of genetic testing. A muscle biopsy may be done to remove a small piece of muscle for examination under a microscope. Blood tests looking for increased levels of certain special proteins called muscle enzymes are used to check for muscle damage. [1] [7]

What causes muscle weakness in children?

Heart and breathing problems also begin in the teen years and lead to serious, life threatening complications. DMD is caused by genetic changes ( DNA variants) in the DMD gene.

Why do boys with DMD have breathing problems?

By the early teens, most boys with DMD are using a wheelchair. Breathing problems occur due to weakness of the diaphragm and the other muscles around the lungs. Scoliosis and tight joints ( contractures) may develop as muscle loss gets worse.

How to find a genetics specialist?

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

What is delayed motor development?

Delayed motor development (taking longer to learn to sit, stand, or walk)

Is DMD inherited?

DMD is inherited in an X-linked recessive pattern and may occur in people who do not have a family history of DMD. Diagnosis of DMD is based on the symptoms, clinical exam, and the result of a biopsy to remove a small piece of muscle for examination under a microscope.

How does Duchenne muscular dystrophy occur?

Duchenne muscular dystrophy is caused by changes in a single gene in our body. Duchenne can be passed from parent to child, or it can be the result of random spontaneous genetic mutations, which may occur during any pregnancy. In fact, about one out of every three cases occurs in families with no previous history of Duchenne.

How is Duchenne inherited?

In order to understand how Duchenne can occur one or more times in a family, it is helpful to understand some basic genetics. We as humans have 23 pairs of chromosomes, or 46 total, in every cell of our body:

What is the role of dystrophin?

Duchenne muscular dystrophy is caused by a change in the dystrophin gene. Genes are small pieces of DNA that contain the instructions for how to make a protein. The dystrophin gene is basically a recipe for how to make the dystrophin protein.

What is a female with one dystrophin gene mutation called?

Females with one dystrophin gene mutation are called carriers . Carriers have an increased chance of having sons with Duchenne and daughters who are carriers. Females carriers are usually not affected with Duchenne because they make enough of the dystrophin protein.

How is dystrophin passed through the family?

The dystrophin mutation is passed through the family. The mutation is passed through the family by carrier females, who may not know that they are carriers. It is likely that a mutation is passing through the family if a person with Duchenne has an affected relative.

Why does Duchenne occur?

Duchenne occurs because there is not enough dystrophin protein in the muscle cells or the dystrophin protein present does not work correctly.

What happens if a woman carries a mutation in the gene that encodes for her dystrophin?

If a woman carries a mutation in the gene that encodes for her dystrophin, with each pregnancy she will have a 50% chance of passing on the gene with the mutation. Each time a carrier woman has a son, there is a 50% chance (or 1 out of 2) that he will be affected with Duchenne. Each time a carrier woman has a daughter, ...

How many babies are born with Duchenne muscular dystrophies?

Duchenne and Becker muscular dystrophies together affect 1 in 3,500 to 5,000 newborn males worldwide. Between 400 and 600 boys in the United States are born with these conditions each year.

Why are Duchenne and Becker muscular dystrophies classified as dystrophinopathies?

Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies. Learn more about the gene associated with Duchenne and Becker muscular dystrophy. Expand Section.

What causes Becker muscular dystrophy?

Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy. Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, ...

How do Duchenne muscular dystrophy and Becker muscular dystrophy differ?

The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.

What is the DMD gene?

Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells.

How long does Becker muscular dystrophy last?

Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.

What is the name of the condition that weakens the heart muscle?

Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence.

What is the most common form of muscular dystrophy?

Duchenne muscular dystrophy ( DMD) is a genetic condition characterized by progressive weakening of voluntary muscles. DMD worsens more rapidly than other types of muscular dystrophy. It’s also the most common form of muscular dystrophy. The Centers for Disease Control and Prevention. Trusted Source. estimated that one out of every 5,600 ...

What tests can be done to check for muscular dystrophy?

You and your child’s pediatrician may notice that your child’s muscles are weakening and that your child has a lack of coordination. Blood tests and muscle biopsies can confirm a diagnosis of DMD.

How do you know if you have DMD?

The symptoms of DMD generally start to appear between ages 2 and 6. Many children with DMD develop normally during infancy and early childhood. DMD symptoms may include: 1 difficulty walking 2 a loss of ability to walk 3 enlarged calves 4 learning disabilities, which occurs in about one-third of affected individuals 5 a lack of motor skills development 6 fatigue 7 rapidly worsening weakness in the legs, pelvis, arms, and neck

Why can't you prevent DMD before conception?

You can’t prevent DMD before conception because it passes down from the mother. Geneticists are researching technology that may be able to prevent the defect from being passed on, but they haven’t discovered a successful cure.

How long can a person with DMD live?

However, with diligent care, some people with DMD survive into their 30s. In the later stages of the disease, most people with DMD will need full-time care to maintain quality of life. The condition is degenerative, which means that the need for medical care increases as the condition worsens.

What is a DMD?

DMD is a genetic disease. Those who inherit it have a defective gene related to a muscular protein called dystrophin. This protein keeps muscle cells intact. Its absence causes rapid muscular deterioration as a child with DMD grows.

What are the symptoms of DMD?

DMD symptoms may include: difficulty walking. a loss of ability to walk. enlarged calves. learning disabilities, which occurs in about one-third of affected individuals. a lack of motor skills development. fatigue. rapidly worsening weakness in the legs, pelvis, arms, and neck.

How many babies are affected by Duchenne muscular dystrophy?

Duchenne muscular dystrophy mostly affects boys and occurs in one in 3,500 to 5,000 newborns. There is no higher risk for any ethnic group. Children affected by DMD may have some degree of cognitive problems, yet some have average or even higher-than-average intelligence.

What is the cause of DMD?

DMD is a genetic disease caused by a gene on the X chromosome that mothers can pass on to their sons. The gene affects a protein called dystrophin that muscles require to function normally.

What is the most severe muscular dystrophy?

Duchenne muscular dystrophy, or DMD, is associated with the most severe clinical symptoms of all the muscular dystrophies. It is caused by a genetic mutation on one of the mother’s X chromosomes, and researchers have identified some of the affected genes.

What causes muscles to weaken and atrophy?

Muscular dystrophy is a genetic problem that causes muscles to weaken and atrophy (become smaller and waste away).

What is multidisciplinary approach to DMD?

A multidisciplinary approach with a team of specialists with experience in treating DMD can offer your child the chance for longer survival and better quality of life.

How old is too old to have DMD?

DMD most commonly appears in children between 3 and 6 years old. Children may have difficulty walking or getting up from a seated position or from lying down. Parents or caretakers may notice weakness of the shoulder and pelvis, abnormal clumsiness and frequent falling. Other symptoms and signs include:

What is genetic counselor?

A genetics counselor reviews the history of disease with each family, discusses the principles of inheritance and helps weigh risks and benefits of genetic testing of various family members, including the affected child and potentially carrier testing for the mother.

Discovery

Function

Causes

Symptoms

Mechanism

Genetics

Risks

• DMD occurs because the mutated gene fails to produce virtually any functional dystrophin. (Individuals with Becker MD genetic mutations make dystrophin that is partially functional, which protects their muscles from degenerating as badly or as quickly as in DMD.) Although DMD often runs in a family, it's possible for a family with no history of DMD...

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Diagnosis