1. Duchenne Muscular DystrophyDuchenne Muscular Dystrophy
(DMD)(DMD)
Dr. Mohamed AbunadaDr. Mohamed Abunada
Pediatric NeurologyPediatric Neurology
DepartmentDepartment
Dr. Al rantisi specializedDr. Al rantisi specialized
children Hospitalchildren Hospital
2. Muscular DystrophyMuscular Dystrophy
First described in the 1830’s muscularFirst described in the 1830’s muscular
dystrophy is a group of more than 30dystrophy is a group of more than 30
diseases that affect the skeletaldiseases that affect the skeletal
musclesmuscles
These muscles will experience progressiveThese muscles will experience progressive
weakening and eventually degenerationweakening and eventually degeneration
Muscular dystrophy can affect the heart,Muscular dystrophy can affect the heart,
lungs, eyes, spine, brain, endocrinelungs, eyes, spine, brain, endocrine
system, and gastrointestinal system assystem, and gastrointestinal system as
well as other organs.well as other organs.
3. Major ClassificationsMajor Classifications
The dystrophies are a group of geneticThe dystrophies are a group of genetic
myopathies.myopathies.
The usual cause is a defect in a structural proteinThe usual cause is a defect in a structural protein
For most dystrophies, the abnormal gene andFor most dystrophies, the abnormal gene and
gene product are established.gene product are established.
There are eight major classifications of muscularThere are eight major classifications of muscular
dystrophy. Each classification differs by thedystrophy. Each classification differs by the
“extent and distribution of muscle weakness, age“extent and distribution of muscle weakness, age
of onset, rate of progression, severity ofof onset, rate of progression, severity of
symptoms, and family history (including anysymptoms, and family history (including any
pattern of inheritance)” .pattern of inheritance)” .
6. Becker MDBecker MD
Cause is insufficient production of dystrophin,Cause is insufficient production of dystrophin,
a protein that helps keep muscle cells intact.a protein that helps keep muscle cells intact.
Similar to Duchenne MD with a later onset andSimilar to Duchenne MD with a later onset and
slower progressionslower progression
The rate of progressive, symmetric muscleThe rate of progressive, symmetric muscle
atrophyatrophy and weakness varies greatly amongand weakness varies greatly among
affected individualsaffected individuals
7. Emery-Dreifuss MDEmery-Dreifuss MD
Cause is mutations in the genes thatCause is mutations in the genes that
produce emerin, lamin A or lamin C,produce emerin, lamin A or lamin C,
proteins in the membrane thatproteins in the membrane that
surrounds the nucleus of each musclesurrounds the nucleus of each muscle
cell.cell.
Onset is usually by 10 years of age.Onset is usually by 10 years of age.
This disease causes slow butThis disease causes slow but
progressive wasting of the upper armprogressive wasting of the upper arm
and lower leg muscles and symmetricand lower leg muscles and symmetric
weaknessweakness
8. Congenital MDCongenital MD
Cause is genetic mutations affecting some ofCause is genetic mutations affecting some of
the proteins necessary for muscles andthe proteins necessary for muscles and
sometimes for the eyes and or brain. (MEBsometimes for the eyes and or brain. (MEB
Syndrome, Walker Warburg Syndrome)Syndrome, Walker Warburg Syndrome)
Present at birth or evident by age 2Present at birth or evident by age 2
Varies with type; many are slowly progressive;Varies with type; many are slowly progressive;
some shorten life spansome shorten life span
The majority of patients are unable to sit orThe majority of patients are unable to sit or
stand without support, and some affectedstand without support, and some affected
children may never learn to walkchildren may never learn to walk
9.
10. Limb-Girdle Muscular DystrophiesLimb-Girdle Muscular Dystrophies
Autosomally determined face-sparing,Autosomally determined face-sparing,
proximally predominant, progressive muscularproximally predominant, progressive muscular
dystrophiesdystrophies
10% autosomal dominant(6 subtypes, LGMD1A-F)10% autosomal dominant(6 subtypes, LGMD1A-F)
90% autosomal recessive(11 subtypes, LGMD2A-K)90% autosomal recessive(11 subtypes, LGMD2A-K)
Age at onset varies greatly (usually 1Age at onset varies greatly (usually 1stst
– 3– 3rdrd
decade)decade)
Defective proteins coded by mutant genes mayDefective proteins coded by mutant genes may
be detected by immunohistochemistry orbe detected by immunohistochemistry or
immunoblottingimmunoblotting
12. SarcoglycanopathiesSarcoglycanopathies
Clinical presentation:Clinical presentation:
Age of onset and severity is heterogeneous, usuallyAge of onset and severity is heterogeneous, usually
starts between 2 and 20 yearsstarts between 2 and 20 years
Clinically often indistinguishable from Duchenne-Clinically often indistinguishable from Duchenne-
dystrophydystrophy
No cardiac involvementNo cardiac involvement
Diagnosis:Diagnosis:
Normal dystrophin immunostaining, abnormalNormal dystrophin immunostaining, abnormal
immunostaining with sarcoglycansimmunostaining with sarcoglycans
Genetic examination, where availableGenetic examination, where available
13. Myotonic MDMyotonic MD
Cause is a repeated section of DNA on eitherCause is a repeated section of DNA on either
chromosome 19 or chromosome 3.chromosome 19 or chromosome 3.
Onset of the congenital form appears at birth. MoreOnset of the congenital form appears at birth. More
common forms may begin in teen or adult years.common forms may begin in teen or adult years.
Affects the central nervous system and other bodyAffects the central nervous system and other body
systems, including the heart, adrenal glands andsystems, including the heart, adrenal glands and
thyroid, eyes, and gastrointestinal tractthyroid, eyes, and gastrointestinal tract
Symptoms first seen in muscles in the hands and feetSymptoms first seen in muscles in the hands and feet
Distinctive symptoms include muscle tensing, cramps,Distinctive symptoms include muscle tensing, cramps,
or inability to relax muscles.or inability to relax muscles.
14. Duchenne Muscular Dystrophy(DMD)Duchenne Muscular Dystrophy(DMD)
DMD affects mostlyDMD affects mostly malesmales at a rate ofat a rate of 1 in 3,5001 in 3,500
birthsbirths..
There are over 200 types of mutations that can causeThere are over 200 types of mutations that can cause
any one of the forms of muscular dystrophy.any one of the forms of muscular dystrophy.
DMD is theDMD is the most severemost severe andand common typecommon type ofof
muscular dystrophy.muscular dystrophy.
DMD is characterized by the wasting away of muscles.DMD is characterized by the wasting away of muscles.
Diagnosis inDiagnosis in boysboys usually occursusually occurs between 16 monthsbetween 16 months
and 8 years.and 8 years.
Parents are usually the first to notice problem.Parents are usually the first to notice problem.
Death from DMD usually occurs by age of 20.Death from DMD usually occurs by age of 20.
15. DMD Gene and DystrophinDMD Gene and Dystrophin
FunctionFunction
The DMD gene encodes for the proteinThe DMD gene encodes for the protein
dystrophin, found in muscle cells anddystrophin, found in muscle cells and
some neurons.some neurons.
Dystrophin provides strength to muscle cells byDystrophin provides strength to muscle cells by
linking the internal cytoskeleton to the surfacelinking the internal cytoskeleton to the surface
membrane.membrane.
Without this structural support, the cell membraneWithout this structural support, the cell membrane
becomes permeable.becomes permeable.
Under normal wear and tear stem cells within theUnder normal wear and tear stem cells within the
muscle regenerate new muscle cells and repairmuscle regenerate new muscle cells and repair
the damage.the damage.
In DMD the damage to muscle cells is so extremeIn DMD the damage to muscle cells is so extreme
that the supply of stem cells are exhausted andthat the supply of stem cells are exhausted and
repair can no longer occur.repair can no longer occur.
16. Clinical FeaturesClinical Features
Genotype of DMDGenotype of DMD
Females carry the DMDFemales carry the DMD
gene on the Xgene on the X
chromosome.chromosome.
Females are carriers and have aFemales are carriers and have a
50% chance of transmitting the50% chance of transmitting the
disease in each pregnancy.disease in each pregnancy.
Sons who inherit the mutationSons who inherit the mutation
will have the disease.will have the disease.
Daughters that inherit theDaughters that inherit the
mutation will be carriers.mutation will be carriers.
The DMD gene is located onThe DMD gene is located on
the Xp 21 band of the Xthe Xp 21 band of the X
chromosome.chromosome.
17. Genotype of DMDGenotype of DMD
(Cont.)(Cont.)
During the translocation process, a mutationDuring the translocation process, a mutation
occurs.occurs.
Mutations leading to theMutations leading to the absence of dystrophinabsence of dystrophin
Very Large Deletions (lead to absence of dystrophin)Very Large Deletions (lead to absence of dystrophin)
Mutations causingMutations causing reading errorsreading errors (causes a(causes a
degraded, low functioning DMD proteindegraded, low functioning DMD protein
molecule)molecule)
DeletionDeletion
DuplicationDuplication
Point MutationsPoint Mutations
18.
19. Clinical FeaturesClinical Features
Phenotype of DMDPhenotype of DMD
Delays in early childhood stages involvingDelays in early childhood stages involving
muscle use, in 42% of patients.muscle use, in 42% of patients.
Delays in standing aloneDelays in standing alone
Delays in sitting without aidDelays in sitting without aid
Delays in walking (12 to 24 months)Delays in walking (12 to 24 months)
Toe walking or flat footednees.Toe walking or flat footednees.
Child has a hard time climbing.Child has a hard time climbing.
Learning difficulties in 5% of patients.Learning difficulties in 5% of patients.
Speech problems in 3% of patients.Speech problems in 3% of patients.
Leg and calf pain.Leg and calf pain.
Mental development is impaired. IQ’s usuallyMental development is impaired. IQ’s usually
below 75 points.below 75 points.
Memory problemsMemory problems
Carrying out daily functionsCarrying out daily functions
20. Clinical FeaturesClinical Features (Cont.)(Cont.)
Increase in bone fracturesIncrease in bone fractures due to the decreasedue to the decrease
in bone density.in bone density.
Wheelchair bound by 12Wheelchair bound by 12 years of age.years of age.
Cardiomyopathy at 14 to 18 yearsCardiomyopathy at 14 to 18 years..
Few patients live beyond 30 years of age.Few patients live beyond 30 years of age.
RespiratoryRespiratory problems andproblems and cardiomyopathycardiomyopathy leading toleading to
congestive heart failure are the usual cause of death.congestive heart failure are the usual cause of death.
24. Approach to Diagnosis of Childhood MuscularApproach to Diagnosis of Childhood Muscular
DystrophyDystrophy
N o D e l e t i o n
D e t e c t e d
D i a g n o s i s o f D y s t r o p h in o p a t h y ( D M D o r B M D )
D e l e t i o n N o t
I n f o r m a t i v e
f o r S e v e r i ty
D e l e t i o n In f o r m a t i v e
f o r S e v e r i t y .
P o s i t i v e F a m i l y H i s t o r y
D e l e t i o n
D e t e c t e d
D N A A n a l y s is
f o r D y s t r o p h i n
G e n e A b n o r m a l i ty
M a le
A b n o r m a l
D y s t r o p h i n
M e r o s i n a n d
A d h a l i n A n a l y s is
N o r m a l
D y s t r o p h i n
M u s c l e B i o p s y
F e m a le
E l e v a t e d
M u s c u l a r D y s t r o p h y
U n l i k e ly
N o r m a l
C K
M u s c u l a r W e a k n e s s
26. management of DMD and BMDmanagement of DMD and BMD
SYMPTOM MANAGEMENTSYMPTOM MANAGEMENT — In addition to— In addition to
muscle weakness,muscle weakness, cardiaccardiac,, pulmonarypulmonary, and, and
orthopedicorthopedic complications are frequentlycomplications are frequently
associated with DMD and BMD.associated with DMD and BMD.
The anticipation and early detection of organThe anticipation and early detection of organ
involvement is important for optimal therapy.involvement is important for optimal therapy.
Furthermore, patients should be evaluated byFurthermore, patients should be evaluated by
pulmonarypulmonary andand cardiac specialistscardiac specialists prior to anyprior to any
surgery .surgery .
27. American Thoracic Society guidelinesAmerican Thoracic Society guidelines
recommend thatrecommend that
allall patients with DMD should receive thepatients with DMD should receive the
pneumococcal vaccinepneumococcal vaccine and anand an annualannual
influenza vaccination.influenza vaccination. The pneumococcalThe pneumococcal
vaccine can provide immunity for 5 to 10vaccine can provide immunity for 5 to 10
years.years.
Nocturnal mouth intermittent positive pressureNocturnal mouth intermittent positive pressure
Ventilation can be used to treat symptomaticVentilation can be used to treat symptomatic
nocturnal hypoventilation, and respiratorynocturnal hypoventilation, and respiratory
assistance may be used during periods ofassistance may be used during periods of
respiratory infectionrespiratory infection
28. Cardiac diseaseCardiac disease
angiotensin converting enzymeangiotensin converting enzyme (ACE)(ACE) inhibitorsinhibitors
andand beta blockersbeta blockers, to treat asymptomatic left, to treat asymptomatic left
ventricular dysfunction and overt heart failure.ventricular dysfunction and overt heart failure.
EchocardiographyEchocardiography should be obtained aroundshould be obtained around
age 10 years in boys with DMD and BMD andage 10 years in boys with DMD and BMD and
then repeatedthen repeated annuallyannually oror biannuallybiannually..
Cardiac evaluation of female carriers shouldCardiac evaluation of female carriers should
begin after teenage years.begin after teenage years.
29. Orthopedic interventionsOrthopedic interventions
Therapeutic interventions in DMD/BMD areTherapeutic interventions in DMD/BMD are
specifically aimed atspecifically aimed at
1.maintaining function,1.maintaining function,
2.preventing contractures.2.preventing contractures.
The mainstays of physical therapy are passiveThe mainstays of physical therapy are passive
stretching exercises to prevent contractures ofstretching exercises to prevent contractures of
the iliotibial band, the Achilles tendons, andthe iliotibial band, the Achilles tendons, and
flexors of the hip.flexors of the hip.
30.
31. orthopedic interventionsorthopedic interventions
Multiple additional interventions may be used based uponMultiple additional interventions may be used based upon
the patient's requirements and severity of disease:the patient's requirements and severity of disease:
Lightweight plastic ankle-foot orthosesLightweight plastic ankle-foot orthoses should be applied ifshould be applied if
the foot remains in plantar flexion during sleep.the foot remains in plantar flexion during sleep.
Standing and/or walking may be maintained by usingStanding and/or walking may be maintained by using long-long-
leg braces.leg braces.
SurgerySurgery may be performed tomay be performed to release contractures of the hiprelease contractures of the hip
flexors, iliotibial bands, and Achilles tendons.flexors, iliotibial bands, and Achilles tendons.
Standing and ambulation may prevent scoliosis.Standing and ambulation may prevent scoliosis.
Spine surgerySpine surgery to stabilize or correct scoliosis may improveto stabilize or correct scoliosis may improve
patient comfort, particularly for those confined to apatient comfort, particularly for those confined to a
wheelchair, and may benefit pulmonary function .wheelchair, and may benefit pulmonary function .
Orthopedic evaluationsOrthopedic evaluations should monitor for scoliosis andshould monitor for scoliosis and
other complications and surgical interventions should beother complications and surgical interventions should be
utilized as needed.utilized as needed.
Chest and spine radiographyChest and spine radiography should be ordered on an as-should be ordered on an as-
needed basis.needed basis.
32. NutritionNutrition
Exposure toExposure to sunshinesunshine and aand a balanced diet thatbalanced diet that
is rich in vitamin D and calciumis rich in vitamin D and calcium is important tois important to
improve bone density and reduce the risk ofimprove bone density and reduce the risk of
fractures.fractures.
Vitamin D supplementationVitamin D supplementation if the serumif the serum
concentration of vitamin D is less than 20concentration of vitamin D is less than 20
ng/mL is recommended.ng/mL is recommended.
Weight should be monitoredWeight should be monitored and controlled toand controlled to
avoid obesity. It is recommended that patientsavoid obesity. It is recommended that patients
receivereceive routine evaluation by a nutritionistroutine evaluation by a nutritionist..
33. TREATMENTTREATMENT
CorticosteroidsCorticosteroids are the mainstay of treatmentare the mainstay of treatment
forfor DMDDMD and are offered as treatment forand are offered as treatment for
boys who areboys who are over the age of five years.over the age of five years.
PrednisonePrednisone —is beneficial in the treatment—is beneficial in the treatment
of DMD and is associated with a significantof DMD and is associated with a significant
increase in strengthincrease in strength,, muscle functionmuscle function, and, and
pulmonary function.pulmonary function.
Little is known of the effect of prednisone inLittle is known of the effect of prednisone in
patients with BMD.patients with BMD.
34. Practice Parameter:Practice Parameter:
Corticosteroid Treatment OfCorticosteroid Treatment Of
Duchenne Muscular DystrophyDuchenne Muscular Dystrophy
An Evidence-Based Report of the American Academy ofAn Evidence-Based Report of the American Academy of
Neurology and the Child Neurology SocietyNeurology and the Child Neurology Society
Richard T. Moxley III, MD, Stephen Ashwal MD, ShreeRichard T. Moxley III, MD, Stephen Ashwal MD, Shree
Pandya, MS, PT, Anne Connolly, MD, Julaine Florence,Pandya, MS, PT, Anne Connolly, MD, Julaine Florence,
MHS, PT, Katherine Mathews, MD, Lisa Baumbach, MD,MHS, PT, Katherine Mathews, MD, Lisa Baumbach, MD,
Craig McDonald, MD, Michael Sussman, MD,Craig McDonald, MD, Michael Sussman, MD,
Christine Wade, PhD, PTChristine Wade, PhD, PT
Published inPublished in NeurologyNeurology 2005;64:13-202005;64:13-20
35. RecommendationsRecommendations
PrednisonePrednisone has been demonstrated to have ahas been demonstrated to have a
beneficial effect on muscle strength and function inbeneficial effect on muscle strength and function in
boysboys between 5 to 15 years of agebetween 5 to 15 years of age with DMD and shouldwith DMD and should
be offered (at a dose of 0.75 mg/kg/d) as treatmentbe offered (at a dose of 0.75 mg/kg/d) as treatment..
MaintainingMaintaining a dosage of 0.75 mg/kg/da dosage of 0.75 mg/kg/d is optimal; but, ifis optimal; but, if
side effects require a decrease in prednisone, taperingside effects require a decrease in prednisone, tapering
to dosages as low as 0.3 mg/kg/d gives significantto dosages as low as 0.3 mg/kg/d gives significant
improvement.improvement.
Benefits and side effects of corticosteroid therapyBenefits and side effects of corticosteroid therapy
need to be monitored. Timed function tests,need to be monitored. Timed function tests,
pulmonary function tests, and age at loss ofpulmonary function tests, and age at loss of
independent ambulation are useful to assess benefits.independent ambulation are useful to assess benefits.
An offer of treatment with corticosteroids shouldAn offer of treatment with corticosteroids should
include a balanced discussion of potential risks.include a balanced discussion of potential risks.
36.
37. Potential side effects of corticosteroid therapy need to
be assessed:
•Weight gain
•Cushingoid appearance
•Cataracts
•Short stature
•Acne
•Excessive hair growth
•Gastrointestinal symptoms
•Behavioral changes
If excessive weight gain occurs (>20% over estimated
normal weight for height over a 12 month period), based
on available data, it is recommended that the dosage of
prednisone be decreased (to 0.5 mg/kg/d with a further
decrease after 3-4 months to 0.3 mg/kg/d if excessive
weight gain continues).
38. Future Research
Double blind, randomized, controlled studies areDouble blind, randomized, controlled studies are
needed to compare daily treatment with prednisone toneeded to compare daily treatment with prednisone to
other treatment regimens, such as:other treatment regimens, such as:
a)a) higher dose alternate day treatment (5 mg/kg everyhigher dose alternate day treatment (5 mg/kg every
other day)other day)
b)b) intermittent treatment (0.75 mg/kg/d for 10 days –intermittent treatment (0.75 mg/kg/d for 10 days –
stop for 10 days – repeat cycle)stop for 10 days – repeat cycle)
c)c) high dose pulses on weekends (5mg/kg on Fridayhigh dose pulses on weekends (5mg/kg on Friday
and Saturday) andand Saturday) and
d)d) deflazacort (0.9 mg/kg/d).deflazacort (0.9 mg/kg/d).
The goal of these studies is to establish more clearlyThe goal of these studies is to establish more clearly
the optimal dose, optimal age to initiate treatment, andthe optimal dose, optimal age to initiate treatment, and
optimal dose schedule to improve function with theoptimal dose schedule to improve function with the
least possible side effects.least possible side effects.
39. NOVEL THERAPIESNOVEL THERAPIES
Gene therapyGene therapy
Experimental gene therapies are currently underExperimental gene therapies are currently under
evaluation (whether by transplanted myoblastevaluation (whether by transplanted myoblast
or direct genetic manipulation) .or direct genetic manipulation) .
40. CreatineCreatine
Creatine monohydrate has been studied for itsCreatine monohydrate has been studied for its
potential to increase muscle strength in NMD andpotential to increase muscle strength in NMD and
muscular dystrophiesmuscular dystrophies
Creatine treatment was associated with improved gripCreatine treatment was associated with improved grip
strength of the dominant hand and increased fat freestrength of the dominant hand and increased fat free
mass compared with placebo.mass compared with placebo.
In light of the limited data and apparently modestIn light of the limited data and apparently modest
benefit attributed to creatine in the studies,benefit attributed to creatine in the studies,
demonstration of clinically important improvement indemonstration of clinically important improvement in
larger trials is needed before recommending thislarger trials is needed before recommending this
treatment for patients with DMD.treatment for patients with DMD.
41. Stem cell therapyStem cell therapy
The use of stem cells in the treatment ofThe use of stem cells in the treatment of
DMD and BMD is under investigation butDMD and BMD is under investigation but
remains experimentalremains experimental
42. PROGNOSIS (DMD)PROGNOSIS (DMD)
some improvement between three and sixsome improvement between three and six
years of age.years of age.
followed by gradual deterioration, leadingfollowed by gradual deterioration, leading
to wheelchair bounding by age of 12 yearsto wheelchair bounding by age of 12 years
Most patients with DMD die in their lateMost patients with DMD die in their late
teens or twenties from respiratoryteens or twenties from respiratory
insufficiency (most commonly) orinsufficiency (most commonly) or
arrhythmia secondary to cardiomyopathy.arrhythmia secondary to cardiomyopathy.
43. PROGNOSIS (BMD)PROGNOSIS (BMD)
patients with BMD typically remainpatients with BMD typically remain
ambulatory beyond the age of 16 years andambulatory beyond the age of 16 years and
into adult life.into adult life.
they survive beyond the age of 30 years.they survive beyond the age of 30 years.
The most common cause of death is heartThe most common cause of death is heart
failure from dilated cardiomyopathy, whichfailure from dilated cardiomyopathy, which
also causes considerable morbidity in thesealso causes considerable morbidity in these
patients despite their milder skeletal musclepatients despite their milder skeletal muscle
involvementinvolvement
44. BibliographyBibliography
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Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M.
New York: ; c1999.
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Strachan, Tom and Read, Andrew P.
New York and London: ; c1999
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Houben F, Ramaekers FC, Snoeckx LH, Broers JL.Houben F, Ramaekers FC, Snoeckx LH, Broers JL.
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Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy.Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy.
Am Heart J.Am Heart J. 1995 Apr;1995 Apr;
Kanagawa M, Toda T.Kanagawa M, Toda T.
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Multiexon skipping leading to an artificial DMD protein lacking amino acids from exon 45 through 55 could rescue up to 63% ofMultiexon skipping leading to an artificial DMD protein lacking amino acids from exon 45 through 55 could rescue up to 63% of
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Editor's Notes
5 & 6 are adolescent onset
7 – 9 are adult onset
muscle weakness in Becker MD is typically noticed first in the upper arms and shoulders, upper legs, and pelvis.
Early symptoms of Becker MD include walking on one's toes, frequent falls, and difficulty rising from the floor. Calf muscles may appear large and healthy as deteriorating muscle fibers are replaced by fat, and muscle activity may cause cramps in some people.
Contractures in the spine, ankles, knees, elbows, and back of the neck usually precede significant muscle weakness
Nearly all Emery-Dreifuss MD patients have some form of heart problem by age 30, often requiring a pacemaker or other assistive device
Patients often die in mid-adulthood from progressive pulmonary or cardiac failure.
Also known as Landouzy-Dejerine disease, this third most common form of MD is an autosomal dominant disorder
Changes in facial appearance may include the development of a crooked smile, a pouting look, flattened facial features, or a mask-like appearance. Some patients cannot pucker their lips or whistle and may have difficulty swallowing, chewing, or speaking
Patients with congenital MD may develop contractures (chronic shortening of muscles or tendons around joints, which prevents the joints from moving freely), scoliosis, respiratory and swallowing difficulties, and foot deformities
Congenital MD may also affect the central nervous system, causing vision and speech problems, seizures, and structural changes in the brain. Some children with the disorders die in infancy while others may live into adulthood with only minimal disability.
Muscles in the face and the front of the neck are usually first to show weakness and may produce a haggard, "hatchet" face and a thin, swan-like neck
Other symptoms include cardiac complications, difficulty swallowing, droopy eyelids (called ptosis), cataracts, poor vision, early frontal baldness, weight loss, impotence, testicular atrophy, mild mental impairment, and increased sweating