Muscular dystrophy (MD) is a group of genetic disorders Although there is no cure for MD, early diagnosis,
characterized by progressive muscle weakness, supportive therapies, and emerging gene-based
degeneration, and structural abnormalities due to treatments offer hope for improving mobility, quality of
mutations affecting essential muscle proteins. These life, and disease management.
mutations lead to impaired muscle function, necrosis,
and loss of muscle mass, causing significant disability. Genetic Mutations and Muscle Dysfunction
While primarily affecting skeletal muscles, many forms of Muscular dystrophy (MD) is caused by mutations in
MD also impact the cardiovascular, respiratory, and genes responsible for muscle structure and function.
endocrine systems, necessitating multidisciplinary These mutations interfere with the ability of muscle cells
management. to repair and maintain themselves, leading to
progressive muscle weakness and degeneration over
There are multiple types of MD, each with unique genetic time. Different types of MD arise from mutations in
causes, inheritance patterns, and progression rates: different genes, which is why there are multiple forms of
the disease.
Duchenne Muscular Dystrophy (DMD): The most
severe and common childhood-onset MD, caused by Modes of Inheritance
dystrophin gene mutations. It leads to rapid muscle Most cases of MD are inherited, meaning they are
weakness, loss of ambulation by adolescence, and passed down from one or both biological parents. The
cardiopulmonary complications. way a person inherits MD depends on the specific
genetic mutation involved. The three primary inheritance
Becker Muscular Dystrophy (BMD): A milder variant of patterns are:
DMD, with a slower progression and partial dystrophin
production, allowing for prolonged ambulation. Autosomal Recessive Inheritance
● The child must inherit two copies of the faulty
Congenital Muscular Dystrophy (CMD): Present from gene (one from each parent) to develop the
birth, CMD causes severe hypotonia, joint contractures, disease.
and developmental delays, with some subtypes involving ● If a child receives only one mutated gene, they
cognitive impairment. are a carrier and may not develop symptoms but
can pass the gene to their offspring.
Emery-Dreifuss Muscular Dystrophy (EDMD): Affects ● Common in some types of limb-girdle muscular
skeletal and cardiac muscles, causing joint contractures, dystrophy (LGMD) and congenital muscular
progressive weakness, and potentially fatal heart dystrophy (CMD).
complications.
Autosomal Dominant Inheritance
Facioscapulohumeral Muscular Dystrophy (FSHD): ● The condition develops when a child inherits just
Impacts facial, shoulder, and upper arm muscles, often one mutated gene from a parent.
progressing asymmetrically. ● Unlike recessive forms, a person with a dominant
mutation will likely show symptoms of the
Limb-Girdle Muscular Dystrophy (LGMD): A diverse disease.
group affecting hip and shoulder muscles, with variable ● Seen in facioscapulohumeral muscular dystrophy
progression and severity. (FSHD), myotonic dystrophy, and
oculopharyngeal muscular dystrophy (OPMD).
Myotonic Muscular Dystrophy (MTD): The most
common adult-onset MD, marked by progressive X-Linked (Sex-Linked) Inheritance
weakness, myotonia, and systemic complications. ● The faulty gene is located on the X chromosome.
● Since males (XY) have only one X chromosome,
Oculopharyngeal Muscular Dystrophy (OPMD): A they are more likely to develop the disease if they
late-onset type affecting the eyes and throat, leading to inherit the mutation.
ptosis and swallowing difficulties. ● Females (XX) can carry the mutation without
showing severe symptoms, but they may pass it
on to their children.
● Duchenne muscular dystrophy (DMD) and
● Creatinine kinase (CK): Grossly elevated
Becker muscular dystrophy (BMD) are X-linked ● EMG: Myopathic
disorders. ● US: Increased echo
Muscle biopsy:
The Role of Dystrophin ● Progressive changes with time
● Dystrophin is a protein found in the sarcolemma ● Degeneration and regeneration, variation in
of normal muscle. It provides mechanical support fiber size, internal nuclei, proliferation of
adipose and connective tissue
and structural integrity for the muscle membrane ● Degenerating fibers are often observed in
cytoskeleton. clusters, with necrotic fibers surrounded by
● Mutation in the dystrophin gene leads to muscle macrophages and lymphocytes (Deconinck
fiber necrosis. Patients present with clinical and Dan, 2007).
symptoms of myalgias, fatigue, and weakness. Genetics:
● Muscle biopsies help differentiate between ● X-linked recessive, gene location Xp21
● Counseling for carrier status of female relative
dystrophinopathies. In Duchenne muscular
based on CK and application of new advances
dystrophy, dystrophin is absent or markedly in recombinant DNA technology.
deficient. In Becker’s muscular dystrophy, the ● Prenatal diagnosis, chorionic villous biopsy
abnormalities are less severe. Management:
● Prevention of fixed deformities by passive
stretching
DUCHENNE MUSCULAR DYSTROPHY ● Avoid immobilization with acute illnesses or
A steadily progressive, X-linked muscular dystrophy injury
that results from abnormality at the Xp21 gene ● Promotion of ambulation with braces after loss
loci and plasma membrane protein dystrophin of ability to stabilize hips and knees.
deficiency. Chronic dystrophic myopathy is ● Progression of scoliosis will destabilize sitting
characterized by aggressive fibrotic replacement of posture, and the provision of spinal supports
the muscle and eventual failure of regeneration with ● and appropriate seating will stabilize trunk,
muscle fiber death and fiber loss. Absent dystrophin or facilitate arm use and protect skin. Spine
<3% of normal is diagnostic of DMD. surgery should be considered early when the
curvature measures 20 degrees or more.
Age of diagnosis ● Maintain strength and prolong ambulation with
● Within the first 5 years of life for first affected glucocorticoids including prednisone or
child deflazacort
Presenting symptoms: ● Operative treatment of progressive scoliosis
● Delay in walking ● Novel therapies for dystrophin restoration
● Abnormal gait (useful in 13% of DMD patients with nonsense
● Frequent falling mutation): Ataluren, Drisapersen, Eteplirsen
● Difficulty climbing steps
Cardinal clinical signs: ● The average age to wheelchair dependency
● Waddling gait, lordotic posture is approximately 10 years with a range of 7 to
● Abnormal run 13 years. One study showed that all DMD
● Difficulty rising from floor (Gower’s sign) subjects who took ≥9 seconds to ambulate 30
● Inability to hop feet lost ambulation within 1 year.
● Proximal muscle weakness, legs > arms ● Contractures are common in children >13
● Prominence of calves years of age and mostly affect ankle plantar
Associated features: flexors, knee flexors, hip flexors, iliotibial band,
● Cardiomyopathy (EKG abnormality) elbow flexors, and wrist flexors.
● Intellectual retardation (variable) ● Scoliosis: Prevalence varies from 33% to
● Deformities—equinovarus, scoliosis after loss 100% and is related to age. 50% acquire
of ambulation, fixed flexion contractures after scoliosis between ages 12 and 15 years.
loss of ambulation Scoliosis usually develops after 3 to 4 years in
Course and prognosis: the wheelchair though no cause–effect
● Progressive loss of function relationship has been established.
● Loss of ambulation, usually by 8 to 12 years
● Prone to respiratory infections in later stages
● Life expectancy: Late teens, early 20s
Investigations:
BECKER’S MUSCULAR DYSTROPHY
This X-linked muscular dystrophy has a similar clinical ● Prevention of fixed deformity (e.g., equinus) by
pattern and gene locus to Duchenne type passive stretching
but is milder with slower progression. ● Braces for promotion of ambulation if loss of
ability to walk in late stages
● Unlike DMD, dystrophin is present at 20% to ● Prevention and management of scoliosis if
80% normal levels or normal quantity in BMD. chair bound (Dubowitz, 1978)
The dystrophin molecular weight is abnormal
(usually reduced or increased) and results in
anomalous function.
● Becker’s has a later onset and a slower rate of CONGENITAL MUSCULAR DYSTROPHY
progression compared to DMD. ● A heterogeneous group of cases presenting
● Prevalence of BMD is 12 to 27 per million, with with clinical weakness or deformities in early
a lower incidence than DMD. infancy and having variable dystrophic
● BMD patients are able to walk into the late changes in the muscle.
teenage years. In DMD, ambulation is arrested ● Infants present with hypotonia, muscle
earlier. weakness at birth or within the first few months
● BMD and DMD have similar distributions of of life, congenital contractures, and a
weakness. dystrophic pattern on muscle biopsy
● Children exhibit early contractures,
Age of onset: equinovarus deformities, knee flexion
● Variable: Usually after 5 years of age and into contractures, hip flexion contractures, and
adolescence or adult life tightness of wrist flexors and long finger
Presenting symptoms: flexors.
● Difficulty with running or climbing steps
● Cramps on exercise Age of onset:
Cardinal clinical signs: ● At birth or in infancy or early childhood
● Mild functional disability Presenting symptoms:
● Proximal muscle weakness ● Hypotonia and weakness
● Prominence of calves ● Fixed deformities (arthrogryposis)
● Waddling gait, lordosis ● Variable sucking, swallowing, and respiratory
Associated features: difficulty
● Cardiac involvement (mild, variable EKG ● Delayed motor milestones in later onset cases
changes). Around 75% of Becker’s patients Cardinal clinical signs:
have EKG abnormalities. ● General hypotonia and weakness
Course and prognosis: ● Fixed deformities in relation to intrauterine
● Slowly progressive, variable course compared posture
to DMD ● Variable weakness or contractures in later
● Some cases practically static presenting cases
● Ambulation beyond 16 years Associated features:
● Life expectancy dependent on degree of ● Intellectual retardation (especially in
progression and late respiratory deficit Japan—Fukuyama type)
Investigations: ● Dislocation of hips
● CK: Grossly elevated (similar levels to DMD) ● Secondary deformities, for example, scoliosis
● EMG: Myopathic ● Hydrocephalus and fundal changes
● US: Increased echo (variable) (Santavuori type)
Muscle biopsy: Course and prognosis:
● Variable dystrophic changes. Degeneration ● Variable—many cases relatively static
and regeneration ● May show functional improvement with time
● Variable loss of fibers and proliferation of ● May be fatal from respiratory deficit and risk of
adipose or connective tissue. Foci of atrophic superimposed infection
fibers resembling denervation Investigations:
Genetics: ● CK: Variable from moderate elevation to
● X-linked recessive, same locus (Xp21) at DMD normal levels
● Genetic counseling of heterozygote female ● US: Marked increase in muscle echo
carriers on basis of CK, as well as recombinant ● EMG: Myopathic pattern
DNA technology Muscle biopsy:
Management: ● Variable–some show extensive dystrophic
● Promotion of activity changes with marked replacement of muscle
by adipose tissue and variable connective ● Disability relating to shoulder or facial muscles
tissue proliferation. Cardinal clinical signs:
● Others can show mildly myopathic/dystrophic ● Facial weakness—patient cannot whistle
changes.
● Scapular winging
Genetics:
● Autosomal recessive, gene 9q31–33; 6q. ● Shoulder girdle weakness
● Some cases probably sporadic ● “Terracing” of shoulders on abduction
● Some may be sequel to viral or other ● Lordosis and pelvic girdle weakness in some
inflammatory process. families
Management: Associated features:
● Active physiotherapy to encourage mobility ● – – Deafness (variable)
● Passive stretching of “fixed” deformities
● – – Fundal changes (variable)
(especially two joint muscles)
● Surgical correction of residual deformities at Course and prognosis: Very variable:
appropriate stage (e.g., equinovarus correction ● Some may be mild and very slowly
when able to stand) progressive, with normal life span.
● Avoid immobilization that promotes fixed ● Some have more marked progression of lower
deformity. limb weakness and may lose ambulation in
● Supportive treatment for respiratory problems adult life.
● Variable degree of facial muscle weakness
● Variable respiratory deficit in later stages
FACIOSCAPULOHUMERAL MUSCULAR Investigations:
DYSTROPHY ● CK: Normal or slightly elevated
Autosomal dominant dystrophy disorder primarily ● EMG: Normal or myopathic
affecting facial and shoulder girdle muscles. ● US: Variable
● Initial weakness affects facial muscles, Muscle biopsy:
especially the orbicularis oculi, zygomaticus, ● Variable pathological change from focal
and orbicularis oris. The masseter, temporalis, atrophic fibers only to overtly dystrophic picture
extraocular, and pharyngeal muscles with variability in fiber size, splitting of fibers,
characteristically are spared. internal nuclei, and proliferation of connective
● Sensory neural hearing deficit and impaired and adipose tissue
hearing function are more common than ● Some cases have marked inflammatory
expected in FSH. response.
● Posterior and lateral scapular winging, high Genetics:
riding scapula, and hyperlordosis are also ● Autosomal dominant inheritance, gene locus
seen. Hyperlordosis occurs in 20% of patients 4q35
with FSH. FSH patients with scoliosis have ● Marked clinical variability within families.
mild, nonprogressive curves. Subclinical cases may occur.
● Mild restrictive lung disease occurs in nearly ● Genetic counseling needs careful clinical
50% of patients with FSH, with expiratory assessment of all family members to exclude
muscles more affected than inspiratory subclinical members.
muscles. Management:
● Cardiac complications in FSH are rare and ● Promotion of activity
patients generally have normal longevity. There ● Some cases benefit from surgical fixation of
is usually no cognitive deficit. the scapulae to facilitate abduction of the arms
(Dubowitz, 1978).
Age of onset:
● Variable, ranging from early childhood to adult
life
EMERY–DREIFUSS MUSCULAR DYSTROPHY
Presenting symptoms:
This X-linked muscular dystrophy is clinically distinct
● Some cases have trunk and pelvic girdle
from Duchenne and Becker’s types.
weakness and difficulty with locomotion.
● Emerin is the muscle protein deficient in EMD. Genetics:
● EMD usually presents in adolescence or early ● X-linked recessive, gene locus Xq28
adulthood with atrophy in the upper arms and ● Gene not near Duchene and Becker’s
legs due to focal wasting of the calf muscles dystrophy genes
and biceps. ● Counseling of heterozygote females on basis
● The clinical hallmark of EMD is early presence of CK elevation, minor changes on muscle
of contractures of the elbow flexors with ● biopsy, and possible DNA polymorphisms in
limitation of full elbow extension. Heel cord future
tightness with ankle dorsiflexion weakness and Management:
toe walking may also be present. ● Promotion of ambulation
● Tightness of cervical and lumbar spinal ● Prevention of deformities or their progression
extensor muscles, resulting in limitation of neck ● Correction of fixed deformities of ankles if
and trunk flexion, may occur. ambulation is affected.
● Close monitoring of cardiac status—may need
Age of onset: cardiac pacemaker.
● Late childhood, adolescence, or adult life ● Assessment of respiratory function (Dubowitz,
Presenting symptoms: 1978)
● Difficulty with walking/running
● Rigidity of neck or spine
● Cardiac arrhythmia
Cardinal clinical signs: LIMB GIRDLE SYNDROMES
● Early presence of contractures of the elbow Autosomal recessive muscular dystrophy of variable
flexors with limitation of full elbow extension severity that resembles BMD and DMD. These
● Fixed deformities: Equinus of feet, flexion are myopathies characterized by predominantly
deformity of elbows, rigidity of spine with proximal weakness of shoulder and pelvic girdle
limited muscles.
● neck and trunk flexion
● Mild weakness Age of onset:
● Focal wasting of muscles, especially upper ● Wide, from early childhood to adolescence and
arm (biceps and triceps) and lower leg adult life
(gastrocnemii, anterior group) Presenting symptoms:
Associated features: ● Difficulty with gait, running, or climbing steps
● Cardiac arrhythmia, may not be obvious ● Cramps on exercise
clinically or on routine EKG, needs 24-hour Cardinal clinical signs:
Holter monitoring. ● Abnormal gait, lordotic posture
● Nocturnal hypoventilation, respiratory problems ● Functional disability with hopping and rising
Course and prognosis: from floor
● Muscle weakness and functional disability, very ● Variable muscle weakness
slowly progressive ● Deformities after loss of ambulation, as in DMD
● Cardiac involvement may be life-threatening in ● Prominence of calves in some
early adult life. Associated features: No consistent ones
Investigations: Course and prognosis: Very variable:
● CK: Slight to moderate elevation ● Progression is usually slow, but some cases
● EMG: Myopathic can be more severe and even more rapid than
● US: Focal involvement with increase in echo ● Duchenne type.
Muscle biopsy: Investigations:
● Mild dystrophic changes with variability in fiber ● CK: Elevation variable—mild to moderate,
size, internal nuclei, proliferation of connective sometimes gross
tissue, degeneration, or regeneration ● EMG: Myopathic findings
● Foci of atrophic fibers resembling denervation
● US: Variable increase in echo; may show Age of onset:
differential muscle involvement ● Usually adolescence/adult. May be present in
● Chromosome analysis in female cases to at-risk families at an early age.
exclude translocation involving Xp21 site ● Presenting symptoms:
Muscle biopsy: ● Weakness
● Dystrophic changes; variable ● Stiffness
● May be marked variability in fiber size and Cardinal clinical signs:
splitting of fibers ● Voluntary myotonia with sustained grip
● Degeneration and regeneration ● Percussion myotonia of tongue or peripheral
● Proliferation of adipose and connective tissue muscles
Genetics: ● Facial weakness; inability to bury eyelashes
● Autosomal recessive, gene 15q ● Ptosis, frontal balding, hatchet facies
Management: Associated features:
● Promotion of ambulation ● Cataracts
● Prevention and treatment of deformities ● Delayed intellectual development
(Dubowitz, 1978) Course and prognosis:
● Affected children identified in at-risk families
are often symptom-free. They may later
develop the full adult syndrome, but severity is
MYOTONIC MUSCULAR DYSTROPHY: extremely variable, even within a family.
STEINERT’S DISEASE OR DYSTROPHIA ● Prognosis depends on associated
MYOTONICA cardiomyopathy and respiratory problems.
● Autosomal dominant muscular dystrophy with Investigations:
an incidence of one per 8,000. ● EMG: Myotonia plus myopathy
● Syndrome comprised of myotonia, muscle ● EKG: Conduction defects; arrhythmia
weakness/wasting, cataracts, premature ● Ultrasonography: Increased muscle
balding, cardiomyopathy with conduction echogenicity
deficits, gonadal atrophy, and variable Muscle biopsy:
intellectual deficit and dementia. This adult ● In full blown adult type, marked dystrophic
type is the most common, but it may start in changes plus internal nuclei and sarcoplasmic
childhood. In addition, there is a distinct masses
congenital type (most severe form): Genetics:
● Myotonia can be seen with grip myotonia of the ● Autosomal dominant with marked clinical
hand and percussion myotonia. heterogeneity, gene 19q13
● It affects skeletal muscle, smooth muscle, Management:
myocardium, brain, and ocular structures. ● Supportive treatment of dystrophy
Associated findings include frontal baldness ● Encourage activity
and gonadal atrophy, cataracts, and cardiac ● Myotonia not usually a problem (Dubowitz,
dysrhythmia. 1978)
● Characteristic facial features include long, thin
face with temporal and masseter muscle
wasting.
● MMD characteristically exhibits greater distal
than proximal weakness with initial weakness
often in the ankle dorsiflexors, evertors,
inverters, and hand muscles.
● Cardiac involvement is common with EKG
abnormalities in 70% to 75% of patients, with
sudden death in <5% of patients.
● IQ is often significantly reduced.