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Duchenne Muscular Dystrophy

Muscular Dystrophy Pseudohypertrophic Childhood

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy, caused by a mutation in the dystrophin gene.

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Presentation

The presentation varies according to the age. The milestones related to mobility like walking, crawling and climbing steps are all delayed compared to a typical toddler.

Large and bulky calf muscles are seen in toddlers. Parents should notice that it is a false hypertrophy and is an alarming sign. Pseudo hypertrophy is seen due to abnormality of the calf muscle. A study found that children with Duchenne muscular dystrophy did not start walking till the age of 18 months or beyond. In a study conducted by Dubowitz and colleagues, 74% children manifested symptoms of Duchenne muscular dystrophy by 4 years of age. By the age of 5, awareness about the condition increased as difficulties were experiences in multiple school-related activities like climbing stairs, getting into the bus, etc [1].

During preschool, parents often complain that the child falls repeatedly while making attempts to walk. This is due to lack of strength in muscles. Children tend to seem lazy, clumsy and will avoid climbing stairs. Toe walking is a compensatory feature noticed in affected children as there is weakness of the calf muscles.

Psychometric analyses of children with Duchenne muscular dystrophy has shown that despite adequate and equalized educational opportunities, the average Intelligent Quotient (IQ) is about 85 points in contrast to the 105 points of healthy populations as identified with the help of Weschsler Adult Intelligence Scale (WAIS) [5] [6] [7].

As the child starts growing, muscle weakness is noticed in the pelvic muscles and the shoulders more prominently than the rest of the muscles. Children often need assistance while raising their hands. High energy movements like jumping and hoping are an extremely difficult task for the child. Generally, proximal muscle weakness is noticed earlier followed by distal muscle weakness. There is pseudohypertrophy of tongue (macroglossia in 30% cases) and calf muscles (60% cases). The muscle is replaced by fat and connective tissue leading to the enlarged appearance with no capability for movements. Lastly, the child may develop deformities like scoliosis.

An important sign to look out for is the Gower’s sign which is the typical fashion in which a child with Duchenne muscular dystrophy rises from a seated position on the ground. First, the body weight is shifted on the hands and the knees, followed by raising the hips up against gravity and then finally standing up. There are contractures of the various tendons of the body visible in later years. Children often get relegated to a wheel chair by the age of 12 years; initially to avoid exertion but later it becomes a necessity for movement.

Weakness
  • Muscle weakness grade varied as follows: patient 1 showed asymmetrical bilateral proximal upper and lower extremities weakness, patient 2 showed asymmetrical bilateral upper extremities weakness similar to scapulohumoral muscular dystrophy, and patient[ncbi.nlm.nih.gov]
  • Generally, proximal muscle weakness is noticed earlier followed by distal muscle weakness. There is pseudohypertrophy of tongue (macroglossia in 30% cases) and calf muscles (60% cases).[symptoma.com]
  • The clinical symptoms of muscle weakness usually begin at childhood. The main symptoms of this disorder are gradually muscular weakness. The affected patients have inability to standing up and walking.[ncbi.nlm.nih.gov]
  • Duchenne muscular dystrophy (DMD) is an X-linked form of muscular dystrophy characterized by progressive limb-girdle distribution of muscle weakness.[ncbi.nlm.nih.gov]
Falling
  • Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds.[ncbi.nlm.nih.gov]
  • Four of the five deteriorated rapidly and died within 36 h after falling. X-rays for fractures were negative. Four of the five patients were taking corticosteroids daily. All five patients fulfilled the clinical criteria for Fat Embolism Syndrome.[ncbi.nlm.nih.gov]
  • During the initial period of surgery, while in the prone position, peak inspiratory pressure (PIP) suddenly increased from 20-21 to 38-41 cmH2O, wheezing sounds were heard on auscultation of both lungs, and his blood pressure began to fall.[ncbi.nlm.nih.gov]
  • However, at age 3 he presented his first symptom, a tendency to fall, had difficulty in rising from the floor and in walking on his toes. At age 4 he had a waddling gait and could no longer climb stairs.[ncbi.nlm.nih.gov]
  • […] in toddlers, enlarged calf muscles may be apparent at about three to six years of age, they may appear to be clumsy in their movements, and start to have problems with climbing stairs, getting up from the floor, difficulty with running and frequent falls[novita.org.au]
Developmental Delay
  • Besides, she presented with an unusually early beginning of muscular dystrophy symptoms with infantile-onset motor developmental delay, intellectual disability and early calf muscular hypertrophy.[ncbi.nlm.nih.gov]
  • The proband had bilateral DRS with otherwise normal ocular motility; he also had developmental delay, mild mental retardation, and seizures.[ncbi.nlm.nih.gov]
  • Additional early signs and symptoms include: Developmental delay Muscle weakness Clumsiness Waddling gait Difficulty or inability to perform activities such as climbing stairs, running, and/or jumping Enlarged calf muscles Poor standing posture Learning[pfizer.com]
  • Clinical description Onset occurs in early childhood, and affected boys may show a delay in motor milestones or global developmental delay. Children with DMD generally never achieve the ability to run or jump.[orpha.net]
Wheelchair Bound
  • Children suffering from this disease eventually become wheelchair bound and die in their late teens. Paediatricians caring for the child with Duchenne Muscular Dystrophy in resource poor settings face a lot challenges.[ncbi.nlm.nih.gov]
  • Patients become wheelchair bound and develop respiratory muscle weakness. As dystrophin is also important for heart muscle function, the heart can become weakened and develop arrhythmias due to the dystrophin mutation.[stanfordhealthcare.org]
  • The life expectancy was very low and many were wheelchair bound from an early age.[thetab.com]
  • Progressive muscle weakness often causes Duchenne patients to become wheelchair bound before the age of 12. As the disease worsens, the weakening respiratory muscles lead to respiratory failure.[biomarin.com]
  • When upper-extremity involvement manifests in later stages of Duchenne MD, it is symmetrical and, along with distal weakness, usually follows a rapid worsening of the child's condition toward being wheelchair bound.[emedicine.medscape.com]
Difficulty Climbing Stairs
  • Physical Exam Symptoms progressive weakness affecting proximal muscles first (begins with gluteal muscle weakness) gait abnormalities delayed walking toe walking clumsy, waddling gait difficulty climbing stairs, hopping, or jumping decreased motor skills[orthobullets.com]
  • This muscle weakness causes a waddling gait and difficulty climbing stairs. Muscle weakness also occurs in the arms, neck, and other areas, but not as severely or as early as in the lower half of the body.[genome.gov]
  • As the condition progresses, muscle weakness leads to functional difficulties (difficulty climbing stairs or rising from a chair).[orpha.net]
Macroglossia
  • This article describes the complex orthodontic treatment of a 22-year-old patient with Duchenne muscular dystrophy and macroglossia.[ncbi.nlm.nih.gov]
  • There is pseudohypertrophy of tongue (macroglossia in 30% cases) and calf muscles (60% cases). The muscle is replaced by fat and connective tissue leading to the enlarged appearance with no capability for movements.[symptoma.com]
  • […] absent deep tendon reflexes in the upper extremities and patella (though the tendo Achillis reflex remains intact even in the later stages of this disease), pain in the calves with activity ( 30% of patients), pseudohypertrophy of the calf (60%), and macroglossia[emedicine.medscape.com]
Muscle Weakness
  • Generally, proximal muscle weakness is noticed earlier followed by distal muscle weakness. There is pseudohypertrophy of tongue (macroglossia in 30% cases) and calf muscles (60% cases).[symptoma.com]
  • Approximately 8% of female Duchenne muscular dystrophy (DMD) carriers are manifesting carriers and have muscle weakness to some extent.[ncbi.nlm.nih.gov]
  • Duchenne muscular dystrophy (DMD) is an X-linked form of muscular dystrophy characterized by progressive limb-girdle distribution of muscle weakness.[ncbi.nlm.nih.gov]
  • Because of the progressive muscle weakness they experience, patients with Duchenne muscular dystrophy frequently utilize positive-pressure devices to maintain adequate bronchial hygiene and ventilation.[ncbi.nlm.nih.gov]
  • In this context, the most frequent respiratory complication is nocturnal and daytime hypoventilation related to respiratory muscle weakness.[ncbi.nlm.nih.gov]
Myopathy
  • It is associated with a wide variety of myopathic disorders that affect paraspinal muscles, including inflammatory and inherited myopathies. We describe a woman who presented with camptocormia in her eighth decade.[ncbi.nlm.nih.gov]
  • MRI, EMG and NCV were compatible with proximal muscle myopathy. Muscle biopsy on vastus lateralis showed suspicious perifascicular atrophy and infiltration of mono-macrophage lineage cells complicating the diagnosis.[ncbi.nlm.nih.gov]
  • Because of the infiltration of degenerating muscles with… Read More myopathy In myopathy …most common muscular dystrophy is Duchenne’s, an X-chromosome-linked disorder involving progressive destruction of muscle tissue that usually results in death before[britannica.com]
  • An electromyography study showed findings of myopathy in all patients. One patient was diagnosed with a DMD carrier by a muscle biopsy with an immunohistochemical stain (dystrophin).[ncbi.nlm.nih.gov]
Osteoporosis
  • DMD is an X-linked recessive muscle disease with secondary osteoporosis and related frequently occurring fractures. To date, only bisphosphonates have been used to treat osteoporosis in DMD.[ncbi.nlm.nih.gov]
  • In advanced Duchenne muscular dystrophy (DMD), patients with high bone fracture risk due to osteoporosis, it is difficult to measure spinal bone mineral density (BMD) because of maintaining proper posture.[ncbi.nlm.nih.gov]
  • Complications of corticosteroid therapy must be managed and include: weight management, H2 antagonists for gastric protection, regular monitoring and treatment of osteoporosis, and ophthalmic assessment for cataracts and glaucoma.[orpha.net]
  • Osteoporosis People with DMD may develop 'thinning' of the bones (osteoporosis) . This is due to lack of mobility and also to steroid treatment. It is important to prevent osteoporosis as far as possible.[patient.info]
Muscle Contracture
  • Physical therapy and bracing to prevent muscle contractures and orthopedic management of scoliosis are important components of the care plan.[aanem.org]
  • Muscle contractures in the heels, legs. Muscle deformities. Respiratory disorders, including pneumonia and swallowing with food or fluid passing into the lungs (in late stages of the disease).[medlineplus.gov]
  • Steroids and daily stretching are what most doctors recommend, but they have their drawbacks and don't prevent debilitating muscle contractures.[harrisonsfund.com]
  • Muscle contractures occur in the legs, making the muscles unusable because the muscle fibers shorten and fibrosis occurs in connective tissue. Occasionally, there can be pain in the calves. Symptoms usually appear in boys aged 1 to 6.[genome.gov]
Positive Gower's Sign
  • A physical examination revealed proximal muscle weakness, calf hypertrophy, deep tendon hyporflexia and a positive Gower's sign.[ncbi.nlm.nih.gov]
  • The condition progresses rapidly and the child develops a waddling gait and a positive Gower's sign. Climbing stairs becomes difficult and the child begins to fall frequently.[orpha.net]
  • Boys with DMD demonstrate a positive Gowerssign, a maneuver used by individuals with proximal muscle weakness to rise from a seated position. Blood creatine kinase (CK) is elevated.[natera.com]
Waddling Gait
  • At age 4 he had a waddling gait and could no longer climb stairs. A physical examination revealed proximal muscle weakness, calf hypertrophy, deep tendon hyporflexia and a positive Gower's sign.[ncbi.nlm.nih.gov]
  • Additional early signs and symptoms include: Developmental delay Muscle weakness Clumsiness Waddling gait Difficulty or inability to perform activities such as climbing stairs, running, and/or jumping Enlarged calf muscles Poor standing posture Learning[pfizer.com]
  • The condition progresses rapidly and the child develops a waddling gait and a positive Gower's sign. Climbing stairs becomes difficult and the child begins to fall frequently.[orpha.net]
  • There is tendency to waddling gait and difficulty in walking, jumping, hoping etc. The calf muscles appear bulky but it is owing to pseudohypertrophy. The muscle strength is lost as protein is replaced by fat and collagen.[symptoma.com]
Gowers Sign
  • A physical examination revealed proximal muscle weakness, calf hypertrophy, deep tendon hyporflexia and a positive Gower's sign.[ncbi.nlm.nih.gov]
  • Common questions our doctors are asked What is Gower's sign? Gower's sign is an unusual way of standing up from the floor, where a child uses their upper limbs to compensate for weak lower limbs.[rch.org.au]
  • The condition progresses rapidly and the child develops a waddling gait and a positive Gower's sign. Climbing stairs becomes difficult and the child begins to fall frequently.[orpha.net]
Clumsiness
  • Additional early signs and symptoms include: Developmental delay Muscle weakness Clumsiness Waddling gait Difficulty or inability to perform activities such as climbing stairs, running, and/or jumping Enlarged calf muscles Poor standing posture Learning[pfizer.com]
  • DMD typically appears between the ages of two with weakness in the pelvis and upper limbs, resulting in clumsiness, frequent falling, an unusual gait and general weakness. Some patients also have mild mental retardation.[medicinenet.com]
  • They might also notice that their child falls over often, is clumsy and walks on their toes.[healthdirect.gov.au]
  • The course of Duchenne muscular dystrophy The course of Duchenne muscular dystrophy generally is: lateness in learning to walk in toddlers, enlarged calf muscles may be apparent at about three to six years of age, they may appear to be clumsy in their[novita.org.au]
Absent Deep Tendon Reflex
  • […] dystrophy • progressive motor weakness • no calf pseudohypertrophy • CPK levels are only mildly elevated Guillain-Barre syndrome • acute onset of weakness • absent deep tendon reflexes • CPK levels are normal Treatment Nonoperative corticosteroid therapy[orthobullets.com]
  • Additional clinical findings in Duchenne muscular dystrophy Other clinical findings in Duchenne MD include absent deep tendon reflexes in the upper extremities and patella (though the tendo Achillis reflex remains intact even in the later stages of this[emedicine.medscape.com]
Delayed Milestone
  • Boys with DMD present in early childhood with delayed milestones, such as sitting and standing. There is progressive symmetrical proximal muscle weakness and atrophy, calf hypertrophy, persistent toe walking, scoliosis, and an unsteady gait.[natera.com]

Workup

The following biochemical changes are noted in children to diagnose and monitor the condition. Creatinine phosphokinase (CPK) levels are always raised due to muscle breakdown. Other enzymes that might be elevated are serum transaminases, aldolase and lactate dehydrogenase (LDH). The polymerase chain reaction (PCR) technique might be employed to rapidly screen dystrophin gene deletions as it is 98% accurate and can be executed within less than 24 hours.

Electromyography reveals that the muscle weakness is due to destruction rather than damage to the nerve supplying the muscle. Ultrasound is rapidly replacing the electromyography due to its ease, convenience and accuracy. Muscle biopsy reveals absence of dystrophin protein in them and is confirmatory with the definitive histopathological changes. Genetic testing of the child along with the mother should be done to confirm the presence of deletion of the dystrophin gene. Electrocardiography shows strain on the right ventricle, deepened Q waves, inversion of T waves and peaked R waves [8].

Diagnosis can be confirmed by genetic testing only. Recent advances have made it possible to detect the genetic mutation in a pre-natal checkup itself.

Treatment

Treatment of the Duchenne muscular dystrophy is not complete. A child suffering cannot be fully cured and thus treatment is rehabilitative, palliative and symptomatic. First line of treatment is steroids to avoid further inflammation and damage to the muscles. Antibiotics might be given to prevent respiratory infections that are common due to poor respiratory muscle tone. Certain exercises and activities will keep the rest of the muscles free from damage. Total inactivity out of weakness will cause worsening of the disease and should be strictly avoided. Physiotherapy and occupational therapy are important to maintain muscle strength. Contractures can be avoided by regular exercising. Mobility has been enhanced amply with appliances like wheel chairs and braces.

Surgery might be indicated in cases of severe contractures for patient comfort and mobility. Aggressive surgical release might prolong patient’s ambulatory convenience by almost 3.5 years [9]. Complications pertaining to the respiratory and cardiovascular systems occur commonly as the disease progresses and hence respiratory support is essential.

Prognosis

Being a congenital mutation, the prognosis is bad as the disease is not curable and muscle destruction continues as age advances. Earlier, only the voluntary muscles are affected but later respiratory and cardiovascular complications are unavoidable. The patients generally survive only till the age of 25 [1]. The recent advances have made it possible for the patients to survive till their 30s.

Etiology

The dystrophin gene is a large gene present on the X chromosome. The dystrophin gene mutation may be either inherited or acquired due to an injury through germ line transmission. If the mother is a carrier, there is a 50% chance that the son will be affected with Duchenne muscular dystrophy and manifest symptoms and a 50% chance that the daughter will be a carrier. The defect is present on the short-arm of X chromosome [3]. Hoffman and his team located the defective locus in the region of Xp21 on the X chromosome and found that it had almost 2 million bases paired [4].

Epidemiology

Duchenne muscular dystrophy affects males and generally symptoms are seen between the ages 3 to 5 years. It affects 1 in 3500 live male neonates and it results in muscle degeneration and deformity leading to death [1] [2]. Females are always carriers. It is the commonest muscular dystrophy.

Sex distribution
Age distribution

Pathophysiology

The dystrophin protein is responsible for our muscular strength and connection of the cytoskeleton of each muscle fiber. There is absolutely no production of dystrophin protein in a case of Duchenne muscular dystrophy, which is present in all voluntary skeletal as well as smooth muscles like cardiac and respiratory. This leads to alteration in the passage of signals during stress and pooling of calcium ions which deteriorates the muscle membrane’s integrity. The lack of dystrophin produces cellular instability a the links it forms within the muscles which eventually leads to muscle weakness and muscular degeneration which is rapid and irreversible.

There is persistent and progressive leaking of the intracellular components resulting in the elevated levels of enzymes (CPK) creatinine phosphokinase found in the laboratory investigations.

Prevention

There are no guidelines for prevention of Duchenne muscular dystrophy.

Summary

Duchenne muscular dystrophy is a genetic disorder characterized by progressive muscle weakness and degeneration. It is an X-linked recessive disorder. Duchenne muscular dystrophy is one of the nine types of muscular dystrophies affecting people. Since the genetic mutation is X linked, the carriers are generally females and males are more often affected.

Patient Information

Duchenne Muscular Dystrophy is a recessive X linked disorder. The females are always carriers and males are the ones affected. The disease is seen in children of the age group 3 to 6 years.

This disease is extremely fatal as there is absolute lack of production of dystrophin protein in the muscles due to the deletion of the dystrophin gene on the X chromosome.

The disease starts manifesting symptoms like gradually worsening weakness of the muscles, first affecting the proximal and then the distal muscles. This destruction of muscles leads to limited movements. There is tendency to waddling gait and difficulty in walking, jumping, hoping etc. The calf muscles appear bulky but it is owing to pseudohypertrophy. The muscle strength is lost as protein is replaced by fat and collagen.

Early muscular degeneration eventually leads to movement restriction of these children. Mental retardation is seen in many of these children. Duchenne Muscular Dystrophy is a very disabling disease.

Slowly, as age advances, the children tend to have respiratory and cardiovascular complications and might need to be supported on a ventilator for respiratory support. This is the most dangerous complication for children making death imminent.

Prognosis of patients suffering from Duchenne Muscular Dystrophy is poor as the patients live up to the age of 25 maximum. Certain recent advancements in medications and the appliances makes it possible for them to walk in to their 30’s.

Nonetheless, there is no cure for these children and only palliative treatment can be offered to prolong life. Steroids are the choice of medications given. Since it is a genetic mutation and passed on by the mother, people can avoid it by getting the child genetically tested prenatally. Carrier females should compulsorily rule out such abnormalities.

Counseling the parents about the disease transmission and the prognosis of the disease in children is a very important aspect of the treatment.

Exercise and physiotherapy are the mainstay of the treatment as they help prevention of contractures and ease out movements. Bedridden patients will worsen the disease, hence low force exercises should be continued always.

References

Article

  1. Dubowitz V. Muscle Disorders in Childhood. 2nd ed. Philadelphia, Pa: WB Saunders;1995: 34-132.
  2. Emery AE. Duchenne's muscular dystrophy. In: Oxford Monographs on Medical Genetics Series #24. 2nd ed. Oxford, United Kingdom: Oxford University Press;. 1993.
  3. González-Herrera L, Gamas-Trujillo PA, García-Escalante MG, Castillo-Zapata I, Pinto-Escalante D. Identifying deletions in the dystrophin gene and detecting carriers in families with Duchenne's/Becker's muscular dystrophy. Rev Neurol. Jan 16-31 2009;48(2):66-70
  4. Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. Dec 24 1987;51(6):919-28.
  5. Shapiro F, Specht L. The diagnosis and orthopaedic treatment of inherited muscular diseases of childhood. J Bone Joint Surg Am. Mar 1993;75(3):439-54.
  6. Prosser EJ, Murphy EG, Thompson MW. Intelligence and the gene for Duchenne muscular dystrophy. Arch Dis Child. Apr 1969;44(234):221-30
  7. Pane M, Lombardo ME, Alfieri P, D'Amico A, Bianco F, Vasco G, et al. Attention Deficit Hyperactivity Disorder and Cognitive Function in Duchenne Muscular Dystrophy: Phenotype-Genotype Correlation. J Pediatr. May 4 2012
  8. Thrush PT, Allen HD, Viollet L, Mendell JR. Re-examination of the electrocardiogram in boys with Duchenne muscular dystrophy and correlation with its dilated cardiomyopathy. Am J Cardiol. Jan 15 2009;103(2):262-5.
  9. Heckmatt JZ, Dubowitz V, Hyde SA, et al. Prolongation of walking in Duchenne muscular dystrophy with lightweight orthoses: review of 57 cases. Dev Med Child Neurol. Apr 1985;27(2):149-54.

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Last updated: 2018-06-21 20:27