Format

Send to:

Choose Destination

Duchenne muscular dystrophy(DMD)

MedGen UID:
3925
Concept ID:
C0013264
Disease or Syndrome
Synonyms: DMD; Muscular dystrophy, pseudohypertrophic progressive, Duchenne type
SNOMED CT: Duchenne muscular dystrophy (76670001); Pseudohypertrophic muscular dystrophy (76670001); Benign Duchenne muscular dystrophy (387732009); DMD - Duchenne muscular dystrophy (76670001)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): DMD (Xp21.2-21.1)
 
Monarch Initiative: MONDO:0010679
OMIM®: 310200
Orphanet: ORPHA98896

Definition

The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated dilated cardiomyopathy (DCM) when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM. [from GeneReviews]

Additional descriptions

From OMIM
Dystrophin-associated muscular dystrophies range from the severe Duchenne muscular dystrophy (DMD) to the milder Becker muscular dystrophy (BMD; 300376). Mapping and molecular genetic studies showed that both are the result of mutations in the huge gene that encodes dystrophin, also symbolized DMD. Approximately two-thirds of the mutations in both forms are deletions of one or many exons in the dystrophin gene. Although there is no clear correlation found between the extent of the deletion and the severity of the disorder, DMD deletions usually result in frameshift. Boland et al. (1996) studied a retrospective cohort of 33 male patients born between 1953 and 1983. The mean age at DMD diagnosis was 4.6 years; wheelchair dependency had a median age of 10 years; cardiac muscle failure developed in 15% of patients with a median age of 21.5 years; smooth muscle dysfunction in the digestive or urinary tract occurred in 21% and 6% of the patients, respectively, at a median age of 15 years. In this cohort, death occurred at a median age of 17 years. The authors commented that the diagnosis of DMD is being made at an earlier age but survival has not changed.  http://www.omim.org/entry/310200
From MedlinePlus Genetics
Muscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males.\n\nDuchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. 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.\n\nA related condition called X-linked dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy. People with X-linked dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing.\n\nBoth 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. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in most cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.  https://medlineplus.gov/genetics/condition/duchenne-and-becker-muscular-dystrophy

Clinical features

From HPO
Calf muscle pseudohypertrophy
MedGen UID:
374276
Concept ID:
C1839666
Finding
Enlargement of the muscles of the calf due to their replacement by connective tissue or fat.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Abnormal EKG
MedGen UID:
105507
Concept ID:
C0522055
Finding
Abnormal rhythm of the heart.
Arrhythmia
MedGen UID:
167788
Concept ID:
C0855329
Finding
An electrocardiographic finding of a change in cardiac electrical activity.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
IQ 50-70.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased cuvature (anterior concavity) of the lumbar or cervical spine.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Muscular dystrophy
MedGen UID:
44527
Concept ID:
C0026850
Disease or Syndrome
A group of inherited progressive muscle disorders characterized by muscle weakness and eventual death of the muscle tissues. Examples include Duchenne muscular dystrophy, Becker's muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, and limb-girdle muscular dystrophy.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Calf muscle pseudohypertrophy
MedGen UID:
374276
Concept ID:
C1839666
Finding
Enlargement of the muscles of the calf due to their replacement by connective tissue or fat.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
The significant impairment of gas exchange within the lungs resulting in hypoxia, hypercarbia, or both, to the extent that organ tissue perfusion is severely compromised. Causes include chronic obstructive pulmonary disease, asthma, emphysema, acute respiratory distress syndrome, pneumonia, pulmonary edema, pneumothorax, and congestive heart failure. Treatment requires intubation and mechanical ventilation until the time the lungs recover sufficient function.
Hypoventilation
MedGen UID:
469022
Concept ID:
C3203358
Pathologic Function
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase, CPK; EC 2.7.3.2) in the blood. CPK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Duchenne muscular dystrophy in Orphanet.

Professional guidelines

PubMed

Birnkrant DJ, Bushby KM, Amin RS, Bach JR, Benditt JO, Eagle M, Finder JD, Kalra MS, Kissel JT, Koumbourlis AC, Kravitz RM
Pediatr Pulmonol 2010 Aug;45(8):739-48. doi: 10.1002/ppul.21254. PMID: 20597083
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group.
Lancet Neurol 2010 Feb;9(2):177-89. Epub 2009 Nov 27 doi: 10.1016/S1474-4422(09)70272-8. PMID: 19945914
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group.
Lancet Neurol 2010 Jan;9(1):77-93. Epub 2009 Nov 27 doi: 10.1016/S1474-4422(09)70271-6. PMID: 19945913
Birnkrant DJ, Panitch HB, Benditt JO, Boitano LJ, Carter ER, Cwik VA, Finder JD, Iannaccone ST, Jacobson LE, Kohn GL, Motoyama EK, Moxley RT, Schroth MK, Sharma GD, Sussman MD
Chest 2007 Dec;132(6):1977-86. doi: 10.1378/chest.07-0458. PMID: 18079231
American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.
Pediatrics 2005 Dec;116(6):1569-73. doi: 10.1542/peds.2005-2448. PMID: 16322188
Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C; Quality Standards Subcommittee of the American Academy of Neurology.; Practice Committee of the Child Neurology Society.
Neurology 2005 Jan 11;64(1):13-20. doi: 10.1212/01.WNL.0000148485.00049.B7. PMID: 15642897

External

Orphanet, Duchenne muscular dystrophy, 2013

Recent clinical studies

Etiology

Choong Wong S, Joseph S, Capaldi N, Marco MD, Dunne J, Guglieri M, Horrocks I, Straub V, Faisal Ahmed S; UK NorthStar Clinical Network.
Clin Trials 2021 Feb;18(1):39-50. Epub 2020 Oct 4 doi: 10.1177/1740774520958395. PMID: 33012180
Miller NF, Alfano LN, Iammarino MA, Connolly AM, Moore-Clingenpeel M, Powers BR, Tsao CY, Waldrop MA, Flanigan KM, Mendell JR, Lowes LP
Pediatr Neurol 2020 Dec;113:15-20. Epub 2020 Aug 27 doi: 10.1016/j.pediatrneurol.2020.08.013. PMID: 32979653
Hartman AG, Terhorst L, Little N, Bendixen RM
Eur J Paediatr Neurol 2020 May;26:20-28. Epub 2020 Feb 28 doi: 10.1016/j.ejpn.2020.02.012. PMID: 32165079
James KA, Gralla J, Ridall LA, Do TN, Czaja AS, Mourani PM, Ciafaloni E, Cunniff C, Donnelly J, Oleszek J, Pandya S, Price E, Yang ML, Auerbach SR
Cardiol Young 2020 Feb;30(2):171-176. Epub 2020 Jan 22 doi: 10.1017/S1047951119002610. PMID: 31964455
Nozaki F, Kusunoki T, Kumada T, Shibata M, Fujii T
J Stroke Cerebrovasc Dis 2019 Sep;28(9):2453-2458. Epub 2019 Jul 13 doi: 10.1016/j.jstrokecerebrovasdis.2019.06.023. PMID: 31311695

Diagnosis

Choong Wong S, Joseph S, Capaldi N, Marco MD, Dunne J, Guglieri M, Horrocks I, Straub V, Faisal Ahmed S; UK NorthStar Clinical Network.
Clin Trials 2021 Feb;18(1):39-50. Epub 2020 Oct 4 doi: 10.1177/1740774520958395. PMID: 33012180
Rodríguez-Cruz M, Almeida-Becerril T, Atilano-Miguel S, Cárdenas-Conejo A, Bernabe-García M
Am J Phys Med Rehabil 2020 Dec;99(12):1121-1128. doi: 10.1097/PHM.0000000000001500. PMID: 32520799
Shih JA, Folch A, Wong BL
Curr Heart Fail Rep 2020 Jun;17(3):57-66. doi: 10.1007/s11897-020-00456-0. PMID: 32270339
James KA, Gralla J, Ridall LA, Do TN, Czaja AS, Mourani PM, Ciafaloni E, Cunniff C, Donnelly J, Oleszek J, Pandya S, Price E, Yang ML, Auerbach SR
Cardiol Young 2020 Feb;30(2):171-176. Epub 2020 Jan 22 doi: 10.1017/S1047951119002610. PMID: 31964455
Nozaki F, Kusunoki T, Kumada T, Shibata M, Fujii T
J Stroke Cerebrovasc Dis 2019 Sep;28(9):2453-2458. Epub 2019 Jul 13 doi: 10.1016/j.jstrokecerebrovasdis.2019.06.023. PMID: 31311695

Therapy

Domi E, Hoxha M, Prendi E, Zappacosta B
Cells 2021 Jun 3;10(6) doi: 10.3390/cells10061380. PMID: 34205021Free PMC Article
Choong Wong S, Joseph S, Capaldi N, Marco MD, Dunne J, Guglieri M, Horrocks I, Straub V, Faisal Ahmed S; UK NorthStar Clinical Network.
Clin Trials 2021 Feb;18(1):39-50. Epub 2020 Oct 4 doi: 10.1177/1740774520958395. PMID: 33012180
Baeza-Barragán MR, Labajos Manzanares MT, Ruiz Vergara C, Casuso-Holgado MJ, Martín-Valero R
JMIR Mhealth Uhealth 2020 Dec 8;8(12):e21576. doi: 10.2196/21576. PMID: 33289679Free PMC Article
Miller NF, Alfano LN, Iammarino MA, Connolly AM, Moore-Clingenpeel M, Powers BR, Tsao CY, Waldrop MA, Flanigan KM, Mendell JR, Lowes LP
Pediatr Neurol 2020 Dec;113:15-20. Epub 2020 Aug 27 doi: 10.1016/j.pediatrneurol.2020.08.013. PMID: 32979653
James KA, Gralla J, Ridall LA, Do TN, Czaja AS, Mourani PM, Ciafaloni E, Cunniff C, Donnelly J, Oleszek J, Pandya S, Price E, Yang ML, Auerbach SR
Cardiol Young 2020 Feb;30(2):171-176. Epub 2020 Jan 22 doi: 10.1017/S1047951119002610. PMID: 31964455

Prognosis

Wang K, Romm EL, Kouznetsova VL, Tsigelny IF
Molecules 2020 Aug 26;25(17) doi: 10.3390/molecules25173886. PMID: 32858918Free PMC Article
Wasilewska E, Małgorzewicz S, Sobierajska-Rek A, Jabłońska-Brudło J, Górska L, Śledzińska K, Bautembach-Minkowska J, Wierzba J
Medicina (Kaunas) 2020 Aug 24;56(9) doi: 10.3390/medicina56090426. PMID: 32846887Free PMC Article
Kutluk MG, Doğan ÇS
Pediatr Nephrol 2020 Oct;35(10):1953-1958. Epub 2020 May 23 doi: 10.1007/s00467-020-04587-3. PMID: 32447503
Shih JA, Folch A, Wong BL
Curr Heart Fail Rep 2020 Jun;17(3):57-66. doi: 10.1007/s11897-020-00456-0. PMID: 32270339
Nozaki F, Kusunoki T, Kumada T, Shibata M, Fujii T
J Stroke Cerebrovasc Dis 2019 Sep;28(9):2453-2458. Epub 2019 Jul 13 doi: 10.1016/j.jstrokecerebrovasdis.2019.06.023. PMID: 31311695

Clinical prediction guides

Summer SS, Wong BL, Rutter MM, Horn PS, Tian C, Rybalsky I, Shellenbarger KC, Kalkwarf HJ
Muscle Nerve 2021 Feb;63(2):231-238. Epub 2020 Dec 7 doi: 10.1002/mus.27107. PMID: 33104257
Kononets O, Karaiev T, Tkachenko O, Lichman L
Georgian Med News 2020 Dec;(309):64-71. PMID: 33526732
Preethish-Kumar V, Shah A, Kumar M, Ingalhalikar M, Polavarapu K, Afsar M, Rajeswaran J, Vengalil S, Nashi S, Thomas PT, Sadasivan A, Warrier M, Nalini A, Saini J
AJNR Am J Neuroradiol 2020 Jul;41(7):1271-1278. Epub 2020 Jul 2 doi: 10.3174/ajnr.A6604. PMID: 32616576Free PMC Article
Hartman AG, Terhorst L, Little N, Bendixen RM
Eur J Paediatr Neurol 2020 May;26:20-28. Epub 2020 Feb 28 doi: 10.1016/j.ejpn.2020.02.012. PMID: 32165079
James KA, Gralla J, Ridall LA, Do TN, Czaja AS, Mourani PM, Ciafaloni E, Cunniff C, Donnelly J, Oleszek J, Pandya S, Price E, Yang ML, Auerbach SR
Cardiol Young 2020 Feb;30(2):171-176. Epub 2020 Jan 22 doi: 10.1017/S1047951119002610. PMID: 31964455

Recent systematic reviews

Domi E, Hoxha M, Prendi E, Zappacosta B
Cells 2021 Jun 3;10(6) doi: 10.3390/cells10061380. PMID: 34205021Free PMC Article
Baeza-Barragán MR, Labajos Manzanares MT, Ruiz Vergara C, Casuso-Holgado MJ, Martín-Valero R
JMIR Mhealth Uhealth 2020 Dec 8;8(12):e21576. doi: 10.2196/21576. PMID: 33289679Free PMC Article
Łoboda A, Dulak J
Pharmacol Rep 2020 Oct;72(5):1227-1263. Epub 2020 Jul 20 doi: 10.1007/s43440-020-00134-x. PMID: 32691346Free PMC Article
Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G
Orphanet J Rare Dis 2020 Jun 5;15(1):141. doi: 10.1186/s13023-020-01430-8. PMID: 32503598Free PMC Article
Williamson E, Pederson N, Rawson H, Daniel T
Pediatr Phys Ther 2019 Oct;31(4):323-330. doi: 10.1097/PEP.0000000000000648. PMID: 31568374

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center