Becker's muscular dystrophy: Difference between revisions

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'''For patient information, click [[Becker's muscular dystrophy (patient information)|here]]'''
<br />{{SI}}
{{CMG}}; '''Associate Editor(s)-in-Chief:''' Moises Romo, M.D.


{{Infobox_Disease
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| Name          = {{PAGENAME}}
| Image          =
| Caption        =
| DiseasesDB    = 1280
| ICD10          = {{ICD10|G|71|0|g|70}}
| ICD9          = {{ICD9|359.1}}
| ICDO          =
| OMIM          =
| MedlinePlus    = 000706
| MeshID        =
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{{SI}}
{{CMG}}


==Overview==
== Overview[edit | edit source] ==
'''Becker's muscular dystrophy''' (also known as '''''Benign pseudohypertrophic [[muscular dystrophy]]''''') is an [[X-linked recessive]] inherited disorder characterized by slowly progressive muscle weakness of the legs and [[pelvis]].
Former "pseudohypertrophic muscular dystrophy", now Becker's muscular dystrophy, is a genetic neuromuscular condition characterized by slowly progresive weakness and atrophy of skeletal (mostly legs and pelvis) and cardiac muscles.<ref>{{Cite web|url=https://medlineplus.gov/ency/article/000706.htm|title=Becker muscular dystrophy|last=Campellone|first=Joseph V.|date=02/27/2018|website=Medline Plus|archive-url=|archive-date=|dead-url=|access-date=05/24/2020}}</ref> It is a kind of dystrophinopathy inherited in an X-linked recessive fashion.<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/5900/becker-muscular-dystrophy|title=Becker muscular dystrophy|last=|first=|date=05/01/2020|website=Genetic and Rare Diseases Information Center|archive-url=|archive-date=|dead-url=|access-date=05/24/2020}}</ref>


It is a type of dystrophinopathy, which includes a spectrum of muscle diseases in which there is insufficient dystrophin produced in the muscle cells, resulting in instability in the structure of muscle cell membrane. This is caused by [[mutation]]s in the dystrophin [[gene]], which encodes the [[protein]] [[dystrophin]].  Becker's muscular dystrophy is related to [[Duchenne muscular dystrophy]] in that both result from a mutation in the ''dystrophin'' gene, but in Duchenne muscular dystrophy no functional dystrophin is produced making DMD much more severe than BMD. Both Duchenne and Becker's muscular dystrophy have traditionally been called "X-linked" recessive diseases, but in view of modern molecular biology and identification of the dystrophin gene, it might be more appropriate to say they are X-chromosome recessive diseases.  
== Historical Perspective[edit | edit source] ==
Becker's muscular dystrophy was first described by Peter Emil Becker, a German neurologist, psychiatrist and geneticist, in 1953 with his thesis called ‘‘Dystrophia Musculorum Progessiva: A Genetic and Clinical Investigation of the Muscular Dystrophies’’, after his work was interrumpted in 1942 due to WWII recruitment.<ref name="pmid23576413">{{cite journal| author=Zeidman LA, Kondziella D| title=Peter Becker and his Nazi past: the man behind Becker muscular dystrophy and Becker myotonia. | journal=J Child Neurol | year= 2014 | volume= 29 | issue= 4 | pages= 514-9 | pmid=23576413 | doi=10.1177/0883073813482773 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23576413  }}</ref> 


==Eponym==
Before Becker, in the 1860's, French neurologist Guillaume Benjamin Amand Duchenne described in detail a slowly progessive muscular weakness in a boy, later known as Duchenne muscular dystrophy.<ref>{{Cite web|url=http://www.whonamedit.com/doctor.cfm/950.html|title=Guillaume Benjamin Amand Duchenne de Boulogne|last=Kleinert|first=Rudolph|date=|website=Who named it?|archive-url=|archive-date=|dead-url=|access-date=05/25/2020}}</ref><ref name="pmid31789220">{{cite journal| author=Mercuri E, Bönnemann CG, Muntoni F| title=Muscular dystrophies. | journal=Lancet | year= 2019 | volume= 394 | issue= 10213 | pages= 2025-2038 | pmid=31789220 | doi=10.1016/S0140-6736(19)32910-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31789220  }}</ref>
Becker's is named after the German doctor Peter Emil Becker. <ref>{{WhoNamedIt|synd|915}}</ref><ref>P. E. Becker, F. Kiener. Eine neue x-chromosomale Muskeldystrophie. Archiv für Psychiatrie und Nervenkrankheiten, Berlin, 1955, 193: 427-448. </ref><ref>P. E. Becker. Neue Ergebnisse der Genetik der Muskeldystrophien. Acta genetica et statistica medica, 1957, 7: 303-310.</ref>


== Genetics ==   
The association between [[genetic mutations]] and Duchenne [[muscular dystrophy]] was made in 1986.<ref name="pmid3319190">{{cite journal| author=Hoffman EP, Brown RH, Kunkel LM| title=Dystrophin: the protein product of the Duchenne muscular dystrophy locus. | journal=Cell | year= 1987 | volume= 51 | issue= 6 | pages= 919-28 | pmid=3319190 | doi=10.1016/0092-8674(87)90579-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3319190 }}</ref>


[[Image:XlinkRecessive.jpg|left|X-linked recessive inheritance]]
In 1987, [[dystrophin]] gene on [[X chromosome]] were first implicated in the [[pathogenesis]] of Becker's [[muscular dystrophy]].<ref name="pmid33191902">{{cite journal| author=Hoffman EP, Brown RH, Kunkel LM| title=Dystrophin: the protein product of the Duchenne muscular dystrophy locus. | journal=Cell | year= 1987 | volume= 51 | issue= 6 | pages= 919-28 | pmid=3319190 | doi=10.1016/0092-8674(87)90579-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3319190  }}</ref>
<br />


The disorder is inherited with an [[X-linked recessive]] inheritance pattern. The gene is located on the X [[chromosome]]. Since women have two X chromosomes, if one X chromosome has the non-working gene, the second X chromosome will have a working copy of the gene to compensate. In these cases, some women have much milder symptoms because of this ability to compensate.  For example, carrier females of mutations are at increased risk for [[dilated cardiomyopathy]].  Since men have an X ''and'' a Y chromosome and because they don't have another X to compensate for the defective gene, they ''will'' develop [[symptom]]s if they inherit the non-working gene.
== Pathophysiology[edit | edit source] ==


All dystrophinopathes are inherited in an X-linked recessive manner. The risk to the siblings of an affected individual depends upon the carrier status of the mother.  Carrier females have a 50% chance of passing the DMD mutation in each [[pregnancy]]. Sons who inherit the mutation will be affected; daughters who inherit the mutation will be carriers. Men who have Becker's muscular dystrophy can have children, and all their daughters are carriers, but none of the sons will inherit their father's mutation. [[Prenatal testing]] through [[amniocentesis]] or [[chorionic villus sampling]] (CVS) for pregnancies at risk is possible if the DMD mutation is found in a family member or if informative linked markers have been identified.
* The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
* The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
* On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


Becker's muscular dystrophy occurs in approximately 3 to 6 in 100,000 male births. Symptoms usually appear in men at about ages 8-25, but may sometimes begin later. The average age of becoming unable to walk is 25-70. Women rarely develop symptoms.
Becker's muscular dystrophy is caused by a mutation in the gene DMD, one of the largest genes in humans.<ref name="pmid243054476">{{cite journal| author=Wicklund MP| title=The muscular dystrophies. | journal=Continuum (Minneap Minn) | year= 2013 | volume= 19 | issue= 6 Muscle Disease | pages= 1535-70 | pmid=24305447 | doi=10.1212/01.CON.0000440659.41675.8b | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24305447  }}</ref> This gene encodes for the 3685Y aminoacid protein called dystrophin, wich can be found in skeletal and cardiac muscle, among other tisues. <ref name="pmid243054475">{{cite journal| author=Wicklund MP| title=The muscular dystrophies. | journal=Continuum (Minneap Minn) | year= 2013 | volume= 19 | issue= 6 Muscle Disease | pages= 1535-70 | pmid=24305447 | doi=10.1212/01.CON.0000440659.41675.8b | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24305447  }}</ref>


[[Genetic counseling]] is indicated for individuals or families who may carry this condition.


==Symptoms==
DMD and BMD are inherited in an X-linked recessive fashion, but in roughly 20% to 30% of cases, a mother does not test positive for the mutation in DMD. This is due to a high rate of new mutations, false maternity, and to germ-line mosaicism (in which the mutation is present in some tissues, such as ovaries, but not others, such as skeletal muscle). Because of the possibility of germ-line mosaicism, negative genetic testing in a mother does not preclude the possibility of an affected boy in a subsequent pregnancy. For this indication, preimplantation genetic testing is available.<ref name="pmid243054472">{{cite journal| author=Wicklund MP| title=The muscular dystrophies. | journal=Continuum (Minneap Minn) | year= 2013 | volume= 19 | issue= 6 Muscle Disease | pages= 1535-70 | pmid=24305447 | doi=10.1212/01.CON.0000440659.41675.8b | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24305447  }}</ref>


# Muscle weakness, slowly progressive (Difficulty running, hopping, jumping; Progressive difficulty walking)
'''BMD.''' The BMD phenotype occurs when some dystrophin is produced, usually resulting from deletions or duplications that juxtapose in-frame exons, some splicing variants, and most non-truncating single-base changes that result in translation of a protein product with intact N and C termini. The shorter-than-normal dystrophin protein molecule, which retains partial function, produces the milder BMD phenotype.<ref name="pmid2030129810">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>
# Ability to walk may continue into adulthood (up to age 80)
# Frequent falls
# Difficulty [[respiration (physiology)|breathing]]
# Non progressive cognitive dysfunction only in rare cases: not as common as in duchenne because the brain only needs small amounts of dystrophin
# [[Skeleton|Skeletal]] deformities, [[chest]] and [[back]] ([[scoliosis]])
# Muscle deformities (contractions of [[heel]]s, legs; Pseudohypertrophy of [[calf muscle]]s)
# [[Fatigue (physical)|Fatigue]]
# [[Heart disease]]


People with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass ([[wasting]]). Muscle weakness also occurs in the arms, neck, and other areas, but not as noticeably severe as in the lower half of the body.
== Clinical Features[edit | edit source] ==
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.<ref name="pmid203012986">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>


Calf muscles initially enlarge during the ages of 5-15 (an attempt by the body to compensate for loss of muscle strength), but the enlarged muscle tissue is eventually replaced by [[fat]] and [[connective tissue]] (pseudohypertrophy) as the legs become less used (use of wheelchair).
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.<ref name="pmid203012985">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>


Muscle contractions occur in the legs and heels, causing inability to use the muscles because of shortening of muscle fibers and [[fibrosis]] of connective tissue. [[Bone]]s may develop abnormally, causing skeletal deformities of the chest and other areas.
CNS involvement is not common in MDs and intelligence is usually preserved.<ref name="SarkozyBushby2014">{{cite journal|last1=Sarkozy|first1=A.|last2=Bushby|first2=K.|last3=Mercuri|first3=E.|title=Muscular Dystrophies|year=2014|doi=10.1016/B978-0-12-801238-3.05597-5}}</ref>


[[Cardiomyopathy]] (damage to the heart) does not occur as commonly with this disorder as it does with Duchenne's muscular dystrophy. Cognitive problems may accompany the disorder, but they are not inevitable and do not worsen as the disorder progresses.
'''Becker muscular dystrophy (BMD)'''


==Signs and tests == 
* Progressive symmetric muscle weakness (proximal > distal) often with calf hypertrophy; weakness of quadriceps femoris in some cases the only sign
* Activity-induced cramping (present in some individuals)
* Flexion contractures of the elbows (if present, late in the course)
* Wheelchair dependency (after age 16 years); although some individuals remain ambulatory into their 30s and in rare cases into their 40s and beyond
* Preservation of neck flexor muscle strength (differentiates BMD from DMD)


The pattern of symptom development resembles that of [[Duchenne's muscular dystrophy]], but with a later, and much slower rate of progression. Noticeable signs of Muscular Dystrophy also include the lack of pectroral and upper arm muscles, especially when the disease is unnoticed through the early teen years. Muscle wasting begins in the legs and pelvis (or core), then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy may occur, but the development of [[congestive heart failure]] or [[arrhythmia]]s (irregular heartbeats) is rare.
Note: The presence of fasciculations or loss of sensory modalities excludes a suspected diagnosis of a dystrophinopathy. Individuals with an intermediate phenotype (outliers) have symptoms of intermediate severity and become wheelchair dependent between ages 13 and 16 years.<ref name="pmid203012987">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>


* The ability to walk may continue to age 40 or older.
* [[Creatine kinase]] (CPK) levels may be elevated.
* An [[electromyography]] (EMG) shows that weakness is caused by destruction of muscle tissue rather than by damage to [[nerve]]s.
* [[Genetic testing]]
*A muscle [[biopsy]] ([[immunohistochemistry]] or [[immunoblotting]]) or genetic test ([[blood test]]) confirms the [[diagnosis]].


===AHA Scientific Statement: Management of Cardiac Involvement Associated With Neuromuscular Diseases===
Females may present with a classic dystrophinopathy or may be asymptomatic carriers.


====Cardiac Evaluation in Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)====
* '''Females with a classic dystrophinopathy.''' The genetic mechanisms that can explain this rare occurrence (and testing to identify the cause) include the following:
** A deletion involving Xp21.2 (microarray [CMA] studies)
** An X-chromosome rearrangement involving Xp21.2 or complete absence of an X chromosome (i.e., Turner syndrome) (cytogenetic studies)
** Uniparental disomy (UPD) of the X chromosome (UPD studies)
** Compound heterozygosity for two ''DMD'' pathogenic variants [Soltanzadeh et al 2010] (deletion/duplication analysis and/or sequence analysis)
** Nonrandom X-chromosome inactivation (XCI). See Genotype-Phenotype Correlations.<ref name="pmid203012989">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>


{| class="wikitable" style="width:80%"
<br />
|-
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' All DMD and BMD patients should have an initial cardiac evaluation with examination, ECG, and imaging performed at diagnosis. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |'''"2.''' Asymptomatic DMD/BMD patients with left ventricular dilation or dysfunction or arrhythmia (eg, supraventricular tachycardia, ventricular ectopy) should be reevaluated at least annually. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |'''"3.''' Symptomatic DMD/BMD patients should be reevaluated more frequently than annually, with testing and frequency determined by the provider and clinical status. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |'''"4.''' Female DMD/BMD carriers should undergo cardiac evaluation by examination, ECG, and noninvasive imaging in the second to third decade of life, with follow-up evaluations every 3 to 5 years thereafter. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |'''"5.''' Echocardiography should be routinely used in the screening and follow-up care of DMD/ BMD patients. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| colspan="1" style="text-align:center; background:LemonChiffon" | [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' Every-2-year cardiac evaluation by examina- tion, ECG, and noninvasive imaging is rea- sonable in asymptomatic DMD/BMD patients <10 years of age, increasing to annual evalu- ation at 10 years of age. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LemonChiffon" |'''"2.''' It is reasonable to consider periodic use of advanced tissue imaging modalities (eg, CMR with contrast) in the care of DMD/BMD patients for assessment of cardiac function, particularly in patients with poor acoustic windows or for assessment of myocardial fibrosis. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LemonChiffon" |'''"3.''' Ambulatory electrocardiographic monitor- ing for patients with DMD/BMD is reasonable every 1 to 3 years, based on age, EF, and clinical assessment. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
| bgcolor="LemonChiffon" |'''"4.''' In the absence of an implantable cardio- verter-de brillator (ICD) or other arrhythmia monitoring, at least annual ambulatory electrocardiographic monitoring is reason- able for patents with DMD/BMD with EF <35% or age ≥17 years. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}


==Treatment ==
== Differentiating [disease name] from other Diseases[edit | edit source] ==


There is no known cure for Becker's muscular dystrophy. Treatment is aimed at control of symptoms to maximize the quality of life.
* [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:


Activity is encouraged. Inactivity (such as [[bed rest]]) can worsen the muscle disease. [[Physical therapy]] may be helpful to maintain muscle strength. [[Orthopedic]] appliances such as braces and [[wheelchair]]s may improve mobility and self-care.
'''Limb-girdle muscular dystrophy''' '''(LGMD)''' is a group of autosomal recessive and autosomal dominant disorders that are clinically similar to DMD but occur in both sexes. Limb-girdle dystrophies are caused by mutation of genes that encode sarcoglycans and other proteins associated with the muscle cell membrane that interact with dystrophin [Mohassel & Bönnemann 2015]. Testing for deficiency of proteins from the transmembrane sarcoglycan complex and of other proteins is indicated in individuals with dystrophin-positive dystrophies. LGMD type 2I phenotypically resembles DMD and BMD and is caused by biallelic pathogenic variants in ''FKRP'' (encoding fukutin-related protein).<ref name="pmid20301298">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>


Genetic counseling may be advisable. Sons of a man with Becker's muscular dystrophy do not develop the disorder, but daughters will be carriers. The daughters' sons may develop the disorder.
'''Emery-Dreifuss muscular dystrophy''' '''(EDMD)''' is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that may include palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure. Age of onset, severity, and progression of the muscle and cardiac involvement show intra- and interfamilial variation. Clinical variability ranges from early and severe presentation in childhood to a late onset and slowly progressive course. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade. Pathogenic variants in three genes are known to cause EDMD: ''EMD'' and ''FHL1'', which cause X-linked EDMD; and ''LMNA'', which causes autosomal dominant EDMD and autosomal recessive EDMD.<ref name="pmid203012982">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>


Immunosuppressant steroids like Prednisone have been known to help slow the progression of Becker Muscular Dystrophy. The drug contributes to an increased production of the protein Utrophin which closely resembles Dystrophin, the protein that is defective in BMD.
'''Spinal muscular atrophy''' '''(SMA)''' is suspected in individuals with poor muscle tone, muscle weakness that spares the face and ocular muscles, and evidence of anterior horn cell involvement, including fasciculations of the tongue and absence of deep tendon reflexes. The onset of weakness ranges from before birth to adolescence or young adulthood. The weakness is symmetric, proximal > distal, and progressive. Poor weight gain with growth failure, restrictive lung disease, scoliosis, joint contractures, and sleep difficulties are common complications. SMA is caused by pathogenic variants in ''SMN1'' and inherited in an autosomal recessive manner.


===MY0-029===
'''Dilated cardiomyopathy''' '''(DCM)''' can be familial or nonfamilial. In a large series in which family studies were performed, one third to one half of individuals had nonfamilial DCM and two thirds had familial DCM. Familial DCM may be inherited in an autosomal dominant, an autosomal recessive, or an X-linked manner. Most familial DCM (probably 80%-90%) appears to be autosomal dominant; X-linked and autosomal recessive forms are less common [Watkins et al 2011].<ref name="pmid203012983">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>
{{Main|Stamulumab}}
MYO-029 is an experimental [[myostatin]] inhibiting drug developed by [[Wyeth|Wyeth Pharmaceuticals]] for the treatment of muscular dystrophy. [[Myostatin]] is a protein that inhibits the growth of muscle tissue, MYO-029 is a recombinant human antibody designed to bind and inhibit the activity of [[myostatin]].  


A 2005/2006 study, which included participants afflicted with Becker's, was completed by Wyeth in Collegeville, PA.
'''Barth syndrome,''' an X-linked disorder caused by mutation of ''TAZ'', is characterized in affected males by cardiomyopathy, neutropenia, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt (most evident in infancy); not all features may be present in a given affected individual. Cardiomyopathy, which is almost always present before age five years, is typically dilated cardiomyopathy with or without endocardial fibroelastosis or left ventricular non-compaction. Heart failure is a significant cause of morbidity and mortality; risk of arrhythmia and sudden death is increased. The non-progressive myopathy predominantly affects the proximal muscles, and results in early motor delays. Prepubertal growth delay is followed by a postpubertal growth spurt with remarkable "catch-up" growth.<ref name="pmid203012984">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>
<br />


==Prognosis ==  
== Screening ==
Becker's muscular dystrophy results in slowly progressive disability. Death can occur in the fifth decade but some patients live to an advanced age of 68 or later.
It is appropriate to evaluate at-risk female family members (i.e., the sisters or maternal female relatives of an affected male and first-degree relatives of a known or possible heterozygous female) in order to identify as early as possible heterozygous females who would benefit from cardiac surveillance (see Surveillance).


==Complications== 
Evaluations can include the following:


* Deformities
* Molecular genetic testing if the ''DMD'' pathogenic variant in the family is known
* Permanent, progressive disability manifested as decreased mobility or decreased ability to care for self
* Serum CK testing if the pathogenic variant in the family is not known. Although serum CK concentration can be normal in carrier females, if elevated, it will support heterozygosity status in a female relative.
* [[Mental illness|Mental impairment]]
* Molecular genetic testing of the at-risk female if an affected male is not available for testing:
* [[Cardiomyopathy]]
** By deletion/duplication analysis first
** [[Noncompaction Cardiomyopathy]]
** If no pathogenic variant is identified, by sequence analysis
* [[Pneumonia]] or other respiratory infections
* Linkage analysis to determine carrier status in at-risk females if (1) the ''DMD'' pathogenic variant in the proband is not known, (2) no ''DMD'' pathogenic variant or serum CK elevation is identified in a carrier female, and (3) the family has more than one affected male with the unequivocal diagnosis of DMD/BMD/''DMD''-associated DCM
* [[Respiratory failure]]
** Linkage studies are based on accurate clinical diagnosis of DMD/BMD/''DMD''-associated DCM in the affected family members and accurate understanding of the genetic relationships in the family.
** Linkage analysis relies on the availability and willingness of family members to be tested.
** Because the markers used for linkage in DMD/BMD/''DMD''-associated DCM are highly informative and lie both within and flanking the ''DMD'' locus, they can be used in most families with DMD/BMD/''DMD''-associated DCM [Kim et al 2002].  Note: (1) The large size of ''DMD'' leads to an appreciable risk of recombination. It has been estimated that the gene itself spans a genetic distance of 12 centimorgans [Abbs et al 1990]; thus, multiple recombination events among different members of a family may complicate the interpretation of a linkage study. (2)Testing by linkage analysis is not possible for families in which there is a single affected male. (3) Testing by linkage analysis may not be widely available on a clinical basis.


==Quality of Life==
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.<ref name="pmid170419065">{{cite journal| author=Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C | display-authors=etal| title=Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. | journal=Hum Mutat | year= 2007 | volume= 28 | issue= 2 | pages= 183-95 | pmid=17041906 | doi=10.1002/humu.20422 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17041906  }}</ref>
The quality of life for patients with Becker's muscular dystrophy need not be impacted by the symptoms of the disorder. With assistive devices, independence can be maintained indefinitely. People affected by Becker's muscular dystrophy can still drive, work, own businesses, and maintain active lifestyles. Those affected by the disorder can also still participate in sports for the disabled, such as wheelchair tennis or Power Soccer.
<br />


=== Prenatal Testing and Preimplantation Genetic Diagnosis ===
'''Molecular genetic testing.''' Once the ''DMD'' pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for a dystrophinopathy are possible.
'''Fetal muscle biopsy.''' In utero fetal muscle biopsy has been used in the prenatal diagnosis of DMD in families with DMD in which the ''DMD'' pathogenic variant is not known [Ladwig et al 2002].
The history of molecular diagnostic testing in DMD and the impact of new techniques including chromosome microarray (CMA) analysis and noninvasive prenatal diagnosis methods are reviewed in various publications [Raymond et al 2010, Xu et al 2015, Parks et al 2016].<ref name="pmid170419066">{{cite journal| author=Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C | display-authors=etal| title=Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. | journal=Hum Mutat | year= 2007 | volume= 28 | issue= 2 | pages= 183-95 | pmid=17041906 | doi=10.1002/humu.20422 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17041906  }}</ref>
<br />
== Epidemiology and Demographics[edit | edit source] ==
* The prevalence of Becker's muscular dystrophy is approximately 3-6 per 100,000 individuals worldwide.
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
=== Age[edit | edit source] ===
* Patients of all age groups may develop [disease name].
* [Disease name] is more commonly observed among patients aged [age range] years old.
* [Disease name] is more commonly observed among [elderly patients/young patients/children].
=== Gender[edit | edit source] ===
Becker's muscular dystrophy affects men almost exclusively.
* [Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
=== Race[edit | edit source] ===
* There is no racial predilection for [disease name].
* [Disease name] usually affects individuals of the [race 1] race.
* [Race 2] individuals are less likely to develop [disease name].
== Risk Factors[edit | edit source] ==
* Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
== Natural History, Complications and Prognosis[edit | edit source] ==
* The majority of patients with [disease name] remain asymptomatic for [duration/years].
* Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
* If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
* Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
* Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].
In the early stages, Duchenne and Becker MD affect the shoulder and upper arm muscles and the muscles of the hips and thighs. These weaknesses lead to difficulty in rising from the floor, climbing stairs, maintaining balance and raising the arms.
== Diagnosis[edit | edit source] ==
=== Diagnostic Criteria[edit | edit source] ===
* The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:* [criterion 1]
:* [criterion 2]
:* [criterion 3]
:* [criterion 4]
=== Symptoms[edit | edit source] ===
* [Disease name] is usually asymptomatic.
* Symptoms of [disease name] may include the following:
:* [symptom 1]
:* [symptom 2]
:* [symptom 3]
:* [symptom 4]
:* [symptom 5]
:* [symptom 6]
=== Physical Examination[edit | edit source] ===
* Patients with [disease name] usually appear [general appearance].
* Physical examination may be remarkable for:
:* [finding 1]
:* [finding 2]
:* [finding 3]
:* [finding 4]
:* [finding 5]
:* [finding 6]
=== Laboratory Findings[edit | edit source] ===
* There are no specific laboratory findings associated with [disease name].
* A [positive/negative] [test name] is diagnostic of [disease name].
* An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
* Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
=== Imaging Findings[edit | edit source] ===
* There are no [imaging study] findings associated with [disease name].
* [Imaging study 1] is the imaging modality of choice for [disease name].
* On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
* [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
=== Other Diagnostic Studies[edit | edit source] ===
* [Disease name] may also be diagnosed using [diagnostic study name].
* Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
The diagnosis of a dystrophinopathy is established in a proband with the characteristic clinical findings and elevated CK concentration and/or by identification of a hemizygous pathogenic variant in ''DMD'' on molecular genetic testing in a male and of a heterozygous pathogenic variant in ''DMD'' on molecular genetic testing in a female. Females may present with a classic dystrophinopathy or may be asymptomatic carriers.<ref name="pmid203012988">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301298 | doi= | pmc= | url= }}</ref>
A dystrophinopathy should be suspected in any male or female patient presenting with progressive limb-girdle weakness, especially if the patient has a positive family history, substantially elevated CK level, or cardiomyopathy. The diagnosis of DMD should be the physician’s first thought when a 3- to 5- year-old boy who is physically slower than his peers presents with toe walking, large calves, neck weakness, a partial Gower’s sign, and a CK level greater than 3000 U/L. CK levels may be elevated 10- to 200-fold. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are also muscle enzymes, are often elevated. This transaminitis reflects muscle involvement rather than liver disease, and this can be verified by checking the liver-specific transaminase +-glutamyltransferase (GGT), which will be normal. In DMD, DNA analysis of the dystrophin gene is the first diagnostic procedure.<ref name="pmid243054473">{{cite journal| author=Wicklund MP| title=The muscular dystrophies. | journal=Continuum (Minneap Minn) | year= 2013 | volume= 19 | issue= 6 Muscle Disease | pages= 1535-70 | pmid=24305447 | doi=10.1212/01.CON.0000440659.41675.8b | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24305447  }}</ref>
In patients with BMD or in manifesting female carriers, weakness may not be as pronounced, the CK level may be lower, and the initial procedure will often be electrodiagnostic testing. The EMG reveals myopathic motor units with or without muscle membrane instability. If the patient has no family history of a dystrophinopathy, then a muscle biopsy may be performed. Immunostaining for the N-terminal, rod, and C-terminal regions of dystrophin will usually reveal diffusely decreased, or patchy, staining of some but not all muscle fiber membranes. Confirmatory testing is through DNA analysis. Mutation analysis consists of analysis for duplications and deletions via multiplex PCR or multiplex ligationdependent probe amplification. If this is negative, then gene sequencing is undertaken. Mutations in DMD causative for DMD and BMD are fairly consistent when assessed across different countries,13Y16 with the composition including 43% to 67% deletions and 9% to 11% duplications of exons, 16% to 26% point mutations, and 5% to 6% splice site mutations. Therapies allowing multiexon skipping from exons 45 through 55 would benefit more than 50% of patients with DMD. Mutations disrupting the reading frame (out-of-frame mutations) in DMD create a truncated RNA transcript that is rapidly degraded. This leads to a virtual absence of dystrophin in muscle and a DMD phenotype. Mutations with maintenance of the reading frame (in-frame mutations) generate shorter or less stable dystrophin. Dystrophin with in-frame mutations retain their amino- and carboxy-terminus domains and thus still maintain the mechanical bridge between actin and "-dystroglycan. Inframe mutations more often lead to a BMD phenotype. In a large series, out-of-frame mutations led to a DMD phenotype in nearly 90% of cases; however, in-frame mutations led to a BMD phenotype in only approximately 60% of cases (Case 2-1).13 <ref name="pmid243054474">{{cite journal| author=Wicklund MP| title=The muscular dystrophies. | journal=Continuum (Minneap Minn) | year= 2013 | volume= 19 | issue= 6 Muscle Disease | pages= 1535-70 | pmid=24305447 | doi=10.1212/01.CON.0000440659.41675.8b | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24305447  }}</ref>
== Treatment[edit | edit source] ==
=== Medical Therapy[edit | edit source] ===
* There is no treatment for [disease name]; the mainstay of therapy is supportive care.
* The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
* [Medical therapy 1] acts by [mechanism of action 1].
* Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
*
*
Physical therapy to promote mobility and prevent contractures
* Exercise
** All ambulatory boys with DMD or those in early non-ambulatory phase should participate in regular gentle exercise to avoid contractures and disuse atrophy.
** Exercise can consist of a combination of swimming pool and recreation-based activities. Swimming can be continued in non-ambulatory patients under close supervision, if medically safe.
** If patients complain of muscle pain during or after exercise, the activity should be reduced and monitoring for myoglobinuria should be carried out. Myoglobinuria within 24 hours after exercise indicates overexertion leading to rhabdomyolysis.<ref name="pmid170419064">{{cite journal| author=Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C | display-authors=etal| title=Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. | journal=Hum Mutat | year= 2007 | volume= 28 | issue= 2 | pages= 183-95 | pmid=17041906 | doi=10.1002/humu.20422 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17041906  }}</ref>
<br />
=== Surgery[edit | edit source] ===
* Surgery is the mainstay of therapy for [disease name].
* [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
* [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
=== Prevention[edit | edit source] ===
* There are no primary preventive measures available for [disease name].
* Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
* Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
Appropriate management of individuals with a dystrophinopathy can prolong survival and improve quality of life.<ref name="pmid170419062">{{cite journal| author=Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C | display-authors=etal| title=Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. | journal=Hum Mutat | year= 2007 | volume= 28 | issue= 2 | pages= 183-95 | pmid=17041906 | doi=10.1002/humu.20422 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17041906  }}</ref>
''Prevention of secondary complications:'' Evaluation by a pulmonologist and cardiologist before surgeries; pneumococcal and influenza immunizations annually; nutrition assessment; physical therapy to promote mobility and prevent contractures; sunshine and a balanced diet rich in vitamin D and calcium to improve bone density and reduce the risk of fractures; weight control to avoid obesity.<ref name="pmid170419067">{{cite journal| author=Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C | display-authors=etal| title=Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. | journal=Hum Mutat | year= 2007 | volume= 28 | issue= 2 | pages= 183-95 | pmid=17041906 | doi=10.1002/humu.20422 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17041906  }}</ref>
'''Cardiomyopathy.''' Recommendations are based on an American Academy of Pediatrics policy statement and various additional publications [American Academy of Pediatrics Section on Cardiology and Cardiac Surgery 2005, Jefferies et al 2005, Viollet et al 2012] and apply to patients with the DMD or BMD phenotype.
* The authors' institution commonly treats children with DMD or BMD early with an ACE inhibitor and/or beta blocker.
* When used in combination, these appear to lead to initial improvement of left ventricular function; however, ACE inhibitors are also used without beta blockers, with similar results [Viollet et al 2012].
* The optimal time to start treatment in DMD is unknown, but most cardiologists will initiate treatment when the left ventricle ejection fraction drops below 55% and fractional shortening is less than 28% [Jefferies et al 2005, Viollet et al 2012].
* Angiotensin II-receptor blockers (ARBs) such as losartan are similarly effective and can be used in cases of poor tolerability of ACE inhibitors [Allen et al 2013].
* In cases of overt heart failure, other heart failure therapies including diuretics and digoxin are used as needed.
* Cardiac transplantation is offered to persons with severe dilated cardiomyopathy and BMD with limited or no clinical evidence of skeletal muscle disease.
'''Scoliosis''' treatment as needed is appropriate. The management of scoliosis involves bracing and surgery. Most patients end up getting a spinal fusion. The use of rods is not contraindicated; therefore, rod and bone grafts are used to fuse the spine. A minority of patients do not develop significant scoliosis and may not require a spinal fusion.
'''Corticosteroid therapy.''' Studies have shown that corticosteroids improve the muscle strength and function of individuals with DMD (see Corticosteroid Therapy in DMD). This therapy remains the treatment of choice for affected individuals between ages five and 15 years. Corticosteroid therapy is not recommended in children before age two years [Bushby et al 2010a]. This treatment is also used in BMD, although the efficacy is less clear (see '''BMD''' below).
The following published recommendations for corticosteroid therapy are in accordance with the national practice parameters developed by the American Academy of Neurology and the Child Neurology Society [Moxley et al 2005] (full text), as well as the DMD Care Considerations Working Group [Bushby et al 2010a].
* Boys with DMD should be offered treatment with prednisone (0.75 mg/kg/day, maximum daily dose: 30-40 mg) or deflazacort (0.9 mg/kg/day, maximum daily dose: 36-39 mg) as soon as plateauing or decline in motor skills is noted, which usually occurs at age 4-8 years. Prior to the initiation of therapy, the potential benefits and risks of corticosteroid treatment should be carefully discussed with each individual.
* To assess benefits of corticosteroid therapy, the following parameters are useful: timed muscle function tests, pulmonary function tests, and age at loss of independent ambulation.
* To assess risks of corticosteroid therapy, maintain awareness of the potential corticosteroid therapy side effects (e.g., weight gain, cushingoid appearance, short stature, decrease in linear growth, acne, excessive hair growth, gastrointestinal symptoms, behavioral changes). There is also an increased frequency of vertebral and long bone fractures with prolonged corticosteroid use [King et al 2007].
* The optimal maintenance dose of prednisone (0.75 mg/kg/day) or deflazacort (0.9 mg/kg/day) should be continued if side effects are not severe. Significant but less robust improvement can be seen with gradual tapering of prednisone to as low as 0.3 mg/kg/day (or ~0.4 mg/kg/day of deflazacort).
* If excessive weight gain occurs (>20% over estimated normal weight for height over a 12-month period), the prednisone dose should be decreased by 25%-33% and reassessed in a few months. If excessive weight gain continues, the dose should be further decreased by an additional 25% to the minimum effective dose cited above after three to four months.
* If significant weight gain or intolerable behavioral side effects occur in patients treated with prednisone, change to deflazacort on a ten-day-on / ten-day-off schedule or a high-dose weekend schedule. In patients on deflazacort, side effects of asymptomatic cataracts and weight gain should be monitored.
'''BMD.''' Information about the efficacy of prednisone in treating individuals with BMD is limited. Many clinicians continue treatment with glucocorticoids after loss of ambulation for the purpose of maintaining upper limb strength, delaying the progressive decline of respiratory and cardiac function, and decreasing the risk of scoliosis. Retrospective data suggest that the progression of scoliosis can be reduced by long-term daily corticosteroid treatment; however, an increased risk for vertebral and lower-limb fractures has been documented [King et al 2007]. Men on steroid therapy were less likely to require spinal surgery [Dooley et al 2010b]. The dose is allowed to drift down to 0.3-0.6 mg/kg/day of prednisone or deflazacort, which is still effective [Bushby et al 2010a].<ref name="pmid170419063">{{cite journal| author=Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C | display-authors=etal| title=Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. | journal=Hum Mutat | year= 2007 | volume= 28 | issue= 2 | pages= 183-95 | pmid=17041906 | doi=10.1002/humu.20422 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17041906  }}</ref>
== References[edit | edit source] ==
==References==
==References==
{{reflist|2}}
<nowiki>{{Reflist|2}}</nowiki>
 
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{{CDC}}


{{Muscular Dystrophy}}
{{Muscular Dystrophy}}

Revision as of 01:44, 26 May 2020


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo, M.D.


Overview[edit | edit source]

Former "pseudohypertrophic muscular dystrophy", now Becker's muscular dystrophy, is a genetic neuromuscular condition characterized by slowly progresive weakness and atrophy of skeletal (mostly legs and pelvis) and cardiac muscles.[1] It is a kind of dystrophinopathy inherited in an X-linked recessive fashion.[2]

Historical Perspective[edit | edit source]

Becker's muscular dystrophy was first described by Peter Emil Becker, a German neurologist, psychiatrist and geneticist, in 1953 with his thesis called ‘‘Dystrophia Musculorum Progessiva: A Genetic and Clinical Investigation of the Muscular Dystrophies’’, after his work was interrumpted in 1942 due to WWII recruitment.[3]

Before Becker, in the 1860's, French neurologist Guillaume Benjamin Amand Duchenne described in detail a slowly progessive muscular weakness in a boy, later known as Duchenne muscular dystrophy.[4][5]

The association between genetic mutations and Duchenne muscular dystrophy was made in 1986.[6]

In 1987, dystrophin gene on X chromosome were first implicated in the pathogenesis of Becker's muscular dystrophy.[7]

Pathophysiology[edit | edit source]

  • The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
  • The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
  • On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
  • On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Becker's muscular dystrophy is caused by a mutation in the gene DMD, one of the largest genes in humans.[8] This gene encodes for the 3685Y aminoacid protein called dystrophin, wich can be found in skeletal and cardiac muscle, among other tisues. [9]


DMD and BMD are inherited in an X-linked recessive fashion, but in roughly 20% to 30% of cases, a mother does not test positive for the mutation in DMD. This is due to a high rate of new mutations, false maternity, and to germ-line mosaicism (in which the mutation is present in some tissues, such as ovaries, but not others, such as skeletal muscle). Because of the possibility of germ-line mosaicism, negative genetic testing in a mother does not preclude the possibility of an affected boy in a subsequent pregnancy. For this indication, preimplantation genetic testing is available.[10]

BMD. The BMD phenotype occurs when some dystrophin is produced, usually resulting from deletions or duplications that juxtapose in-frame exons, some splicing variants, and most non-truncating single-base changes that result in translation of a protein product with intact N and C termini. The shorter-than-normal dystrophin protein molecule, which retains partial function, produces the milder BMD phenotype.[11]

Clinical Features[edit | edit source]

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.[12]

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.[13]

CNS involvement is not common in MDs and intelligence is usually preserved.[14]

Becker muscular dystrophy (BMD)

  • Progressive symmetric muscle weakness (proximal > distal) often with calf hypertrophy; weakness of quadriceps femoris in some cases the only sign
  • Activity-induced cramping (present in some individuals)
  • Flexion contractures of the elbows (if present, late in the course)
  • Wheelchair dependency (after age 16 years); although some individuals remain ambulatory into their 30s and in rare cases into their 40s and beyond
  • Preservation of neck flexor muscle strength (differentiates BMD from DMD)

Note: The presence of fasciculations or loss of sensory modalities excludes a suspected diagnosis of a dystrophinopathy. Individuals with an intermediate phenotype (outliers) have symptoms of intermediate severity and become wheelchair dependent between ages 13 and 16 years.[15]


Females may present with a classic dystrophinopathy or may be asymptomatic carriers.

  • Females with a classic dystrophinopathy. The genetic mechanisms that can explain this rare occurrence (and testing to identify the cause) include the following:
    • A deletion involving Xp21.2 (microarray [CMA] studies)
    • An X-chromosome rearrangement involving Xp21.2 or complete absence of an X chromosome (i.e., Turner syndrome) (cytogenetic studies)
    • Uniparental disomy (UPD) of the X chromosome (UPD studies)
    • Compound heterozygosity for two DMD pathogenic variants [Soltanzadeh et al 2010] (deletion/duplication analysis and/or sequence analysis)
    • Nonrandom X-chromosome inactivation (XCI). See Genotype-Phenotype Correlations.[16]


Differentiating [disease name] from other Diseases[edit | edit source]

  • [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

Limb-girdle muscular dystrophy (LGMD) is a group of autosomal recessive and autosomal dominant disorders that are clinically similar to DMD but occur in both sexes. Limb-girdle dystrophies are caused by mutation of genes that encode sarcoglycans and other proteins associated with the muscle cell membrane that interact with dystrophin [Mohassel & Bönnemann 2015]. Testing for deficiency of proteins from the transmembrane sarcoglycan complex and of other proteins is indicated in individuals with dystrophin-positive dystrophies. LGMD type 2I phenotypically resembles DMD and BMD and is caused by biallelic pathogenic variants in FKRP (encoding fukutin-related protein).[17]

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that may include palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure. Age of onset, severity, and progression of the muscle and cardiac involvement show intra- and interfamilial variation. Clinical variability ranges from early and severe presentation in childhood to a late onset and slowly progressive course. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade. Pathogenic variants in three genes are known to cause EDMD: EMD and FHL1, which cause X-linked EDMD; and LMNA, which causes autosomal dominant EDMD and autosomal recessive EDMD.[18]

Spinal muscular atrophy (SMA) is suspected in individuals with poor muscle tone, muscle weakness that spares the face and ocular muscles, and evidence of anterior horn cell involvement, including fasciculations of the tongue and absence of deep tendon reflexes. The onset of weakness ranges from before birth to adolescence or young adulthood. The weakness is symmetric, proximal > distal, and progressive. Poor weight gain with growth failure, restrictive lung disease, scoliosis, joint contractures, and sleep difficulties are common complications. SMA is caused by pathogenic variants in SMN1 and inherited in an autosomal recessive manner.

Dilated cardiomyopathy (DCM) can be familial or nonfamilial. In a large series in which family studies were performed, one third to one half of individuals had nonfamilial DCM and two thirds had familial DCM. Familial DCM may be inherited in an autosomal dominant, an autosomal recessive, or an X-linked manner. Most familial DCM (probably 80%-90%) appears to be autosomal dominant; X-linked and autosomal recessive forms are less common [Watkins et al 2011].[19]

Barth syndrome, an X-linked disorder caused by mutation of TAZ, is characterized in affected males by cardiomyopathy, neutropenia, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt (most evident in infancy); not all features may be present in a given affected individual. Cardiomyopathy, which is almost always present before age five years, is typically dilated cardiomyopathy with or without endocardial fibroelastosis or left ventricular non-compaction. Heart failure is a significant cause of morbidity and mortality; risk of arrhythmia and sudden death is increased. The non-progressive myopathy predominantly affects the proximal muscles, and results in early motor delays. Prepubertal growth delay is followed by a postpubertal growth spurt with remarkable "catch-up" growth.[20]

Screening

It is appropriate to evaluate at-risk female family members (i.e., the sisters or maternal female relatives of an affected male and first-degree relatives of a known or possible heterozygous female) in order to identify as early as possible heterozygous females who would benefit from cardiac surveillance (see Surveillance).

Evaluations can include the following:

  • Molecular genetic testing if the DMD pathogenic variant in the family is known
  • Serum CK testing if the pathogenic variant in the family is not known. Although serum CK concentration can be normal in carrier females, if elevated, it will support heterozygosity status in a female relative.
  • Molecular genetic testing of the at-risk female if an affected male is not available for testing:
    • By deletion/duplication analysis first
    • If no pathogenic variant is identified, by sequence analysis
  • Linkage analysis to determine carrier status in at-risk females if (1) the DMD pathogenic variant in the proband is not known, (2) no DMD pathogenic variant or serum CK elevation is identified in a carrier female, and (3) the family has more than one affected male with the unequivocal diagnosis of DMD/BMD/DMD-associated DCM
    • Linkage studies are based on accurate clinical diagnosis of DMD/BMD/DMD-associated DCM in the affected family members and accurate understanding of the genetic relationships in the family.
    • Linkage analysis relies on the availability and willingness of family members to be tested.
    • Because the markers used for linkage in DMD/BMD/DMD-associated DCM are highly informative and lie both within and flanking the DMD locus, they can be used in most families with DMD/BMD/DMD-associated DCM [Kim et al 2002]. Note: (1) The large size of DMD leads to an appreciable risk of recombination. It has been estimated that the gene itself spans a genetic distance of 12 centimorgans [Abbs et al 1990]; thus, multiple recombination events among different members of a family may complicate the interpretation of a linkage study. (2)Testing by linkage analysis is not possible for families in which there is a single affected male. (3) Testing by linkage analysis may not be widely available on a clinical basis.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.[21]

Prenatal Testing and Preimplantation Genetic Diagnosis

Molecular genetic testing. Once the DMD pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for a dystrophinopathy are possible.

Fetal muscle biopsy. In utero fetal muscle biopsy has been used in the prenatal diagnosis of DMD in families with DMD in which the DMD pathogenic variant is not known [Ladwig et al 2002].

The history of molecular diagnostic testing in DMD and the impact of new techniques including chromosome microarray (CMA) analysis and noninvasive prenatal diagnosis methods are reviewed in various publications [Raymond et al 2010, Xu et al 2015, Parks et al 2016].[22]

Epidemiology and Demographics[edit | edit source]

  • The prevalence of Becker's muscular dystrophy is approximately 3-6 per 100,000 individuals worldwide.
  • In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age[edit | edit source]

  • Patients of all age groups may develop [disease name].
  • [Disease name] is more commonly observed among patients aged [age range] years old.
  • [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender[edit | edit source]

Becker's muscular dystrophy affects men almost exclusively.

  • [Gender 1] are more commonly affected with [disease name] than [gender 2].
  • The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race[edit | edit source]

  • There is no racial predilection for [disease name].
  • [Disease name] usually affects individuals of the [race 1] race.
  • [Race 2] individuals are less likely to develop [disease name].

Risk Factors[edit | edit source]

  • Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis[edit | edit source]

  • The majority of patients with [disease name] remain asymptomatic for [duration/years].
  • Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
  • If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
  • Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
  • Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

In the early stages, Duchenne and Becker MD affect the shoulder and upper arm muscles and the muscles of the hips and thighs. These weaknesses lead to difficulty in rising from the floor, climbing stairs, maintaining balance and raising the arms.

Diagnosis[edit | edit source]

Diagnostic Criteria[edit | edit source]

  • The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
  • [criterion 1]
  • [criterion 2]
  • [criterion 3]
  • [criterion 4]

Symptoms[edit | edit source]

  • [Disease name] is usually asymptomatic.
  • Symptoms of [disease name] may include the following:
  • [symptom 1]
  • [symptom 2]
  • [symptom 3]
  • [symptom 4]
  • [symptom 5]
  • [symptom 6]

Physical Examination[edit | edit source]

  • Patients with [disease name] usually appear [general appearance].
  • Physical examination may be remarkable for:
  • [finding 1]
  • [finding 2]
  • [finding 3]
  • [finding 4]
  • [finding 5]
  • [finding 6]

Laboratory Findings[edit | edit source]

  • There are no specific laboratory findings associated with [disease name].
  • A [positive/negative] [test name] is diagnostic of [disease name].
  • An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
  • Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings[edit | edit source]

  • There are no [imaging study] findings associated with [disease name].
  • [Imaging study 1] is the imaging modality of choice for [disease name].
  • On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
  • [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies[edit | edit source]

  • [Disease name] may also be diagnosed using [diagnostic study name].
  • Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

The diagnosis of a dystrophinopathy is established in a proband with the characteristic clinical findings and elevated CK concentration and/or by identification of a hemizygous pathogenic variant in DMD on molecular genetic testing in a male and of a heterozygous pathogenic variant in DMD on molecular genetic testing in a female. Females may present with a classic dystrophinopathy or may be asymptomatic carriers.[23]


A dystrophinopathy should be suspected in any male or female patient presenting with progressive limb-girdle weakness, especially if the patient has a positive family history, substantially elevated CK level, or cardiomyopathy. The diagnosis of DMD should be the physician’s first thought when a 3- to 5- year-old boy who is physically slower than his peers presents with toe walking, large calves, neck weakness, a partial Gower’s sign, and a CK level greater than 3000 U/L. CK levels may be elevated 10- to 200-fold. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are also muscle enzymes, are often elevated. This transaminitis reflects muscle involvement rather than liver disease, and this can be verified by checking the liver-specific transaminase +-glutamyltransferase (GGT), which will be normal. In DMD, DNA analysis of the dystrophin gene is the first diagnostic procedure.[24]

In patients with BMD or in manifesting female carriers, weakness may not be as pronounced, the CK level may be lower, and the initial procedure will often be electrodiagnostic testing. The EMG reveals myopathic motor units with or without muscle membrane instability. If the patient has no family history of a dystrophinopathy, then a muscle biopsy may be performed. Immunostaining for the N-terminal, rod, and C-terminal regions of dystrophin will usually reveal diffusely decreased, or patchy, staining of some but not all muscle fiber membranes. Confirmatory testing is through DNA analysis. Mutation analysis consists of analysis for duplications and deletions via multiplex PCR or multiplex ligationdependent probe amplification. If this is negative, then gene sequencing is undertaken. Mutations in DMD causative for DMD and BMD are fairly consistent when assessed across different countries,13Y16 with the composition including 43% to 67% deletions and 9% to 11% duplications of exons, 16% to 26% point mutations, and 5% to 6% splice site mutations. Therapies allowing multiexon skipping from exons 45 through 55 would benefit more than 50% of patients with DMD. Mutations disrupting the reading frame (out-of-frame mutations) in DMD create a truncated RNA transcript that is rapidly degraded. This leads to a virtual absence of dystrophin in muscle and a DMD phenotype. Mutations with maintenance of the reading frame (in-frame mutations) generate shorter or less stable dystrophin. Dystrophin with in-frame mutations retain their amino- and carboxy-terminus domains and thus still maintain the mechanical bridge between actin and "-dystroglycan. Inframe mutations more often lead to a BMD phenotype. In a large series, out-of-frame mutations led to a DMD phenotype in nearly 90% of cases; however, in-frame mutations led to a BMD phenotype in only approximately 60% of cases (Case 2-1).13 [25]

Treatment[edit | edit source]

Medical Therapy[edit | edit source]

  • There is no treatment for [disease name]; the mainstay of therapy is supportive care.
  • The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
  • [Medical therapy 1] acts by [mechanism of action 1].
  • Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Physical therapy to promote mobility and prevent contractures

  • Exercise
    • All ambulatory boys with DMD or those in early non-ambulatory phase should participate in regular gentle exercise to avoid contractures and disuse atrophy.
    • Exercise can consist of a combination of swimming pool and recreation-based activities. Swimming can be continued in non-ambulatory patients under close supervision, if medically safe.
    • If patients complain of muscle pain during or after exercise, the activity should be reduced and monitoring for myoglobinuria should be carried out. Myoglobinuria within 24 hours after exercise indicates overexertion leading to rhabdomyolysis.[26]


Surgery[edit | edit source]

  • Surgery is the mainstay of therapy for [disease name].
  • [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
  • [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention[edit | edit source]

  • There are no primary preventive measures available for [disease name].
  • Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
  • Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

Appropriate management of individuals with a dystrophinopathy can prolong survival and improve quality of life.[27]


Prevention of secondary complications: Evaluation by a pulmonologist and cardiologist before surgeries; pneumococcal and influenza immunizations annually; nutrition assessment; physical therapy to promote mobility and prevent contractures; sunshine and a balanced diet rich in vitamin D and calcium to improve bone density and reduce the risk of fractures; weight control to avoid obesity.[28]


Cardiomyopathy. Recommendations are based on an American Academy of Pediatrics policy statement and various additional publications [American Academy of Pediatrics Section on Cardiology and Cardiac Surgery 2005, Jefferies et al 2005, Viollet et al 2012] and apply to patients with the DMD or BMD phenotype.

  • The authors' institution commonly treats children with DMD or BMD early with an ACE inhibitor and/or beta blocker.
  • When used in combination, these appear to lead to initial improvement of left ventricular function; however, ACE inhibitors are also used without beta blockers, with similar results [Viollet et al 2012].
  • The optimal time to start treatment in DMD is unknown, but most cardiologists will initiate treatment when the left ventricle ejection fraction drops below 55% and fractional shortening is less than 28% [Jefferies et al 2005, Viollet et al 2012].
  • Angiotensin II-receptor blockers (ARBs) such as losartan are similarly effective and can be used in cases of poor tolerability of ACE inhibitors [Allen et al 2013].
  • In cases of overt heart failure, other heart failure therapies including diuretics and digoxin are used as needed.
  • Cardiac transplantation is offered to persons with severe dilated cardiomyopathy and BMD with limited or no clinical evidence of skeletal muscle disease.

Scoliosis treatment as needed is appropriate. The management of scoliosis involves bracing and surgery. Most patients end up getting a spinal fusion. The use of rods is not contraindicated; therefore, rod and bone grafts are used to fuse the spine. A minority of patients do not develop significant scoliosis and may not require a spinal fusion.

Corticosteroid therapy. Studies have shown that corticosteroids improve the muscle strength and function of individuals with DMD (see Corticosteroid Therapy in DMD). This therapy remains the treatment of choice for affected individuals between ages five and 15 years. Corticosteroid therapy is not recommended in children before age two years [Bushby et al 2010a]. This treatment is also used in BMD, although the efficacy is less clear (see BMD below).

The following published recommendations for corticosteroid therapy are in accordance with the national practice parameters developed by the American Academy of Neurology and the Child Neurology Society [Moxley et al 2005] (full text), as well as the DMD Care Considerations Working Group [Bushby et al 2010a].

  • Boys with DMD should be offered treatment with prednisone (0.75 mg/kg/day, maximum daily dose: 30-40 mg) or deflazacort (0.9 mg/kg/day, maximum daily dose: 36-39 mg) as soon as plateauing or decline in motor skills is noted, which usually occurs at age 4-8 years. Prior to the initiation of therapy, the potential benefits and risks of corticosteroid treatment should be carefully discussed with each individual.
  • To assess benefits of corticosteroid therapy, the following parameters are useful: timed muscle function tests, pulmonary function tests, and age at loss of independent ambulation.
  • To assess risks of corticosteroid therapy, maintain awareness of the potential corticosteroid therapy side effects (e.g., weight gain, cushingoid appearance, short stature, decrease in linear growth, acne, excessive hair growth, gastrointestinal symptoms, behavioral changes). There is also an increased frequency of vertebral and long bone fractures with prolonged corticosteroid use [King et al 2007].
  • The optimal maintenance dose of prednisone (0.75 mg/kg/day) or deflazacort (0.9 mg/kg/day) should be continued if side effects are not severe. Significant but less robust improvement can be seen with gradual tapering of prednisone to as low as 0.3 mg/kg/day (or ~0.4 mg/kg/day of deflazacort).
  • If excessive weight gain occurs (>20% over estimated normal weight for height over a 12-month period), the prednisone dose should be decreased by 25%-33% and reassessed in a few months. If excessive weight gain continues, the dose should be further decreased by an additional 25% to the minimum effective dose cited above after three to four months.
  • If significant weight gain or intolerable behavioral side effects occur in patients treated with prednisone, change to deflazacort on a ten-day-on / ten-day-off schedule or a high-dose weekend schedule. In patients on deflazacort, side effects of asymptomatic cataracts and weight gain should be monitored.

BMD. Information about the efficacy of prednisone in treating individuals with BMD is limited. Many clinicians continue treatment with glucocorticoids after loss of ambulation for the purpose of maintaining upper limb strength, delaying the progressive decline of respiratory and cardiac function, and decreasing the risk of scoliosis. Retrospective data suggest that the progression of scoliosis can be reduced by long-term daily corticosteroid treatment; however, an increased risk for vertebral and lower-limb fractures has been documented [King et al 2007]. Men on steroid therapy were less likely to require spinal surgery [Dooley et al 2010b]. The dose is allowed to drift down to 0.3-0.6 mg/kg/day of prednisone or deflazacort, which is still effective [Bushby et al 2010a].[29]

References[edit | edit source]

References

{{Reflist|2}}

Template:Muscular Dystrophy it:Distrofia muscolare di Becker nl:Becker spierdystrofie no:Beckers muskeldystrofi fi:Beckerin lihasdystrofia


Template:WikiDoc Sources

  1. ↑ Campellone, Joseph V. (02/27/2018). "Becker muscular dystrophy". Medline Plus. Retrieved 05/24/2020. Check date values in: |access-date=, |date= (help)
  2. ↑ "Becker muscular dystrophy". Genetic and Rare Diseases Information Center. 05/01/2020. Retrieved 05/24/2020. Check date values in: |access-date=, |date= (help)
  3. ↑ Zeidman LA, Kondziella D (2014). "Peter Becker and his Nazi past: the man behind Becker muscular dystrophy and Becker myotonia". J Child Neurol. 29 (4): 514–9. doi:10.1177/0883073813482773. PMID 23576413.
  4. ↑ Kleinert, Rudolph. "Guillaume Benjamin Amand Duchenne de Boulogne". Who named it?. Retrieved 05/25/2020. Check date values in: |access-date= (help)
  5. ↑ Mercuri E, Bönnemann CG, Muntoni F (2019). "Muscular dystrophies". Lancet. 394 (10213): 2025–2038. doi:10.1016/S0140-6736(19)32910-1. PMID 31789220.
  6. ↑ Hoffman EP, Brown RH, Kunkel LM (1987). "Dystrophin: the protein product of the Duchenne muscular dystrophy locus". Cell. 51 (6): 919–28. doi:10.1016/0092-8674(87)90579-4. PMID 3319190.
  7. ↑ Hoffman EP, Brown RH, Kunkel LM (1987). "Dystrophin: the protein product of the Duchenne muscular dystrophy locus". Cell. 51 (6): 919–28. doi:10.1016/0092-8674(87)90579-4. PMID 3319190.
  8. ↑ Wicklund MP (2013). "The muscular dystrophies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1535–70. doi:10.1212/01.CON.0000440659.41675.8b. PMID 24305447.
  9. ↑ Wicklund MP (2013). "The muscular dystrophies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1535–70. doi:10.1212/01.CON.0000440659.41675.8b. PMID 24305447.
  10. ↑ Wicklund MP (2013). "The muscular dystrophies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1535–70. doi:10.1212/01.CON.0000440659.41675.8b. PMID 24305447.
  11. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  12. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  13. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  14. ↑ Sarkozy, A.; Bushby, K.; Mercuri, E. (2014). "Muscular Dystrophies". doi:10.1016/B978-0-12-801238-3.05597-5.
  15. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  16. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  17. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  18. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  19. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  20. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  21. ↑ Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C; et al. (2007). "Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene". Hum Mutat. 28 (2): 183–95. doi:10.1002/humu.20422. PMID 17041906.
  22. ↑ Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C; et al. (2007). "Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene". Hum Mutat. 28 (2): 183–95. doi:10.1002/humu.20422. PMID 17041906.
  23. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301298.
  24. ↑ Wicklund MP (2013). "The muscular dystrophies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1535–70. doi:10.1212/01.CON.0000440659.41675.8b. PMID 24305447.
  25. ↑ Wicklund MP (2013). "The muscular dystrophies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1535–70. doi:10.1212/01.CON.0000440659.41675.8b. PMID 24305447.
  26. ↑ Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C; et al. (2007). "Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene". Hum Mutat. 28 (2): 183–95. doi:10.1002/humu.20422. PMID 17041906.
  27. ↑ Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C; et al. (2007). "Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene". Hum Mutat. 28 (2): 183–95. doi:10.1002/humu.20422. PMID 17041906.
  28. ↑ Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C; et al. (2007). "Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene". Hum Mutat. 28 (2): 183–95. doi:10.1002/humu.20422. PMID 17041906.
  29. ↑ Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C; et al. (2007). "Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene". Hum Mutat. 28 (2): 183–95. doi:10.1002/humu.20422. PMID 17041906.
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