Duchenne muscular dystrophy - Rare Immunology News

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Disease Profile

Duchenne muscular dystrophy

1-9 / 100 000

US Estimated

Europe Estimated

Age of onset

Childhood

ICD-10

G71.0

Inheritance

Duchenne muscular dystrophy (DMD) is inherited in an X-linked recessive pattern.^[1] X-linked means that the gene for the condition is located on the Xchromosome, one of the sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene is enough to cause the condition. X-linked recessive conditions affect males much more frequently than females. Females, who have one altered gene, are called carriers. While, most female carriers have no signs or symptoms of the condition, in rare cases, female carriers may experience some mild signs or symptoms.

A female who carries one X-linked gene alteration has a 50% or 1 in 2 chance of having a son with the condition and a 50% chance of having a daughter who is also a carrier. A male with an X-linked recessive condition cannot pass on the disorder to his sons, but all of his daughters will be carriers.

Sometimes a male child is the first person in a family with the condition. In this case, the gene alteration may have been inherited from the mother, or the alteration may have occurred by chance for the first time in the child (de novo).

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Muscular dystrophy, Duchenne; DMD; Muscular dystrophy, pseudohypertrophic progressive, Duchenne type

Summary

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, or walk and difficulties learning to speak. Muscle weakness is usually noticeable in early childhood. Most children with DMD use a wheelchair by their early teens. 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. 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. The result of genetic testing may also help confirm the diagnosis. While there is no known cure for DMD, there are treatments that can help control symptoms.^[1]^[2]^[3]^[4]^[5]

Becker muscular dystrophy (BMD), a milder form of muscular dystrophy, is also caused by DNA variants in the DMD gene.

Symptoms

The following list includes the most common signs and symptoms in people with Duchenne muscular dystrophy (DMD). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms may include:^[1]^[6]

Delayed motor development (taking longer to learn to sit, stand, or walk)
Enlarged calf muscles (pseudohypertrophy)
Muscle weakness that gets worse over time
Toe walking or waddling gait
Using hands to get up off the floor (Gower's maneuver)
Progressive enlargement of the heart (cardiomyopathy)

The first symptoms of DMD usually occur in boys in early childhood, and include muscle weakness and clumsiness. Developmental milestones such as sitting and walking are often delayed. 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. Breathing problems and progressive enlargement of the heart may become life-threatening. Learning and memory issues (cognitive impairment) may occur in some cases, but do not worsen as DMD progresses.^[1]^[2]^[3]^[4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Calf muscle hypertrophy	Increased size of calf muscles	0008981
Cardiomyopathy	Disease of the heart muscle	0001638
Cognitive impairment	Abnormality of cognition Cognitive abnormality Cognitive defects Cognitive deficits Intellectual impairment Mental impairment [ more ]	0100543
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
Flexion contracture	Flexed joint that cannot be straightened	0001371
Global developmental delay		0001263
Motor delay		0001270
Progressive muscle weakness		0003323
Proximal muscle weakness	Weakness in muscles of upper arms and upper legs	0003701
Respiratory insufficiency	Respiratory impairment	0002093
Scoliosis		0002650
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Specific learning disability		0001328
Waddling gait	'Waddling' gait Waddling walk [ more ]	0002515
Percent of people who have these symptoms is not available through HPO
Abnormal EKG	Abnormal ECG	0003115
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Calf muscle pseudohypertrophy		0003707
Childhood onset	Symptoms begin in childhood	0011463
Congestive heart failure	Cardiac failure Cardiac failures Heart failure [ more ]	0001635
Dilated cardiomyopathy	Stretched and thinned heart muscle	0001644
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Gowers sign		0003391
Hyperlordosis	Prominent swayback	0003307
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Hypoventilation	Slow breathing Under breathing [ more ]	0002791
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Muscular dystrophy		0003560
Muscular hypotonia	Low or weak muscle tone	0001252
Respiratory failure		0002878
X-linked recessive inheritance		0001419

Cause

Duchenne muscular dystrophy (DMD) is occurs when the DMD gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[1]

Different DNA variants in the DMD gene can cause a spectrum of disorders known as dystrophinopathies. The dystrophinopathies can range from very mild symptoms to the more severe symptoms seen in people with DMD. Other dystrophinopathies include Becker muscular dystrophy (BMD) and DMD-associated dilated cardiomyopathy (DCM).^[1]

Diagnosis

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]

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

There is no known cure for Duchenne muscular dystrophy (DMD). Treatment is focused on managing the symptoms of DMD and related complications caused by severe progressive muscle weakness and loss. Medications (such as steroids) may improve the strength and function of muscles.^[8] Additional medications are available for people with DMD with a specific DNA variant. These can help improve muscle strength and function. An enlarged, weakened heart (dilated cardiomyopathy) may be treated with medications, but in severe cases, a heart transplant may be necessary. Assistive devices for breathing difficulties may be needed, especially at night and as the disease progresses.

Specialists who may be involved in the care of someone with DMD may include:^[2]^[3]^[4]

Neurologist
Orthopedist
Cardiologist
Pulmonologist (lung specialist)
Medical geneticist
Physical therapist
Occupational therapist

Management Guidelines

Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Deflazacort(Brand name: Emflaza) Manufactured by PTC Therapeutics
FDA-approved indication: February 2017, deflazacort (Emflaza) was approved for the treatment of Duchenne Muscular Dystrophy in patients 5 years of age and older.
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Eteplirsen(Brand name: Exondys 51) Manufactured by Sarepta Therapeutics, Inc.
FDA-approved indication: September 2016, eteplirsen (Exondys 51) was approved for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.
National Library of Medicine Drug Information Portal
Golodirsen(Brand name: Vyondys 53) Manufactured by Sarepta Therapeutics, Inc.
FDA-approved indication: December 2019, golodirsen (VYONDYS 53) was approved for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.
National Library of Medicine Drug Information Portal

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include severe Becker muscular dystrophy and the limb girdle muscular dystrophies (see these terms). Antenatal diagnosis is possible for families in which the diagnosis has been confirmed by molecular testing. Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Coalition Duchenne
1300 Quail St, Suite 100
Newport Beach , CA 92660
Telephone: +1-714-801-4616
E-mail: [email protected]
Website: https://www.coalitionduchenne.org
CureDuchenne
1400 Quail Street, Suite 110
Newport Beach, CA 92660
Telephone: +1-949-872-2552
E-mail: [email protected]
Website: https://www.cureduchenne.org/
Jett Foundation
36 Cordage Park Circle
Suite 328
Plymouth, MA 02360
Telephone: 781-585-5566
E-mail: [email protected]
Website: https://www.jettfoundation.org/
Parent Project Muscular Dystrophy
401 Hackensack Avenue, 9th Floor
Hackensack, NJ 07601
Toll-free: 1-800-714-5437
Telephone: +1-201-250-8440
Fax: +1-201-250-8435
E-mail: [email protected]
Website: https://www.parentprojectmd.org/
Stand for Duchenne Canada
E-mail: [email protected]
Website: https://duchennecanada.org/

Organizations Providing General Support

Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 1-833-275-6321 (Helpline)
E-mail: [email protected]
Website: https://www.mda.org
Muscular Dystrophy UK
61A Great Suffolk Street
London, SE1 0BU United Kingdom
Toll-free: 0800 652 6352 (Helpline)
Telephone: (+44) 0 020 7803 4800
E-mail: [email protected]
Website: https://www.musculardystrophyuk.org/

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
MedlinePlus Genetics contains information on Duchenne muscular dystrophy. This website is maintained by the National Library of Medicine.
The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Duchenne muscular dystrophy. Click on the link to view a sample search on this topic.

Resources for Kids

BrainPOP presents the topic of Duchenne muscular dystrophy in a short, animated movie. BrainPOP produced this video in partnership with Parent Project Muscular Dystrophy, this four minute video strives to provide kids of all ages with a clear understanding of Duchenne.

References

Darras BT, Urion DK, Ghosh PS. Dystrophinopathies. GeneReviews®. Updated Apr 26, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1119/.
Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management.. Lancet Neurol. 2018; 17(4):347-361. https://pubmed.ncbi.nlm.nih.gov/29395990.
Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management [published correction appears in Lancet Neurol. 2018 Apr 4]. Lancet Neurol. 2018; 17(3):251-267. https://pubmed.ncbi.nlm.nih.gov/29395989.
Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol. 2018; 17(5):445-455. https://pubmed.ncbi.nlm.nih.gov/29398641.
Landfeldt E, Thompson R, Sejersen T, McMillan HJ, Kirschner J, Lochmüller H.. Life expectancy at birth in Duchenne muscular dystrophy: a systematic review and meta-analysis. Eur J Epidemiol. Feb 2020; 10:https://pubmed.ncbi.nlm.nih.gov/32107739.
Rae MG, O'Malley D. Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules. J Neurophysiol. September 1 2016; 116(3):1304-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023417/.
Aartsma-Rus A, Ginjaar IR & Bushby K. The importance of genetic diagnosis for Duchenne muscular dystrophy. BMJ. 53(3):https://jmg.bmj.com/content/53/3/145.
Koeks Z, Bladen CL, Salgado D, van Zwet E, Pogoryelova O, et al. Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database. J Neuromuscul Dis. 2017;4(4):293-306.. 2017; 4(4):293-306. https://pubmed.ncbi.nlm.nih.gov/29125504.
Verhaart IEC, Aartsma-Rus A. Therapeutic developments for Duchenne muscular dystrophy.. Nat Rev Neurol. 2019; 15(7):373-386. https://pubmed.ncbi.nlm.nih.gov/31147635.

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Childhood

G71.0

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Management Guidelines

FDA-Approved Treatments

Related diseases

Organizations

Organizations Supporting this Disease

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

Resources for Kids

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.