Overview
A hereditary generalized muscle disease often manifesting as progressive muscle weakness and atrophy in male children and adolescents. This is a hereditary disease due to mutations in the anti-myasthenic protein gene, with symptomatic supportive therapy as the mainstay of treatment, and some types of patients with some effect of gene therapy.
Definition
Pseudohypertrophic muscular dystrophy is an inherited muscle disorder that includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). It is the most predominant and common type of disease in the group of myotonic dystrophies.
Mutations in the anti-myasthenia gravis protein gene (DMD gene) result in a lack of proteins needed to stabilize muscle cells, leading to destruction of muscle cells and increasing muscle weakness and atrophy.
The disease begins in childhood and adolescence, mostly in boys, and in severe cases can lead to death before age 30 due to respiratory or heart failure.
Some types of DMD can be treated with gene therapy, but there is currently no cure for the disease. However, aggressive treatment can help control symptoms, slow disease progression, and improve quality of life and longevity.
Types or classifications
The disease is divided into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).
Patients with Duchenne-type muscular dystrophy (DMD) have an early onset, rapid progression, and severe symptoms, and patients have a short life expectancy, most often dying before the age of 30.
Patients with Becker muscular dystrophy (BMD) have a relatively late onset of the disease, progress more slowly, have fewer symptoms than DMD, and have a slightly lower life expectancy than healthy people.
Incidence
Only Duchenne muscular dystrophy (DMD) has been identified in China, with a prevalence of about 1 in 4560 surviving male infants.
The incidence of Becker muscular dystrophy (BMD) is about 1/30,000 according to foreign statistics.
It is an X-chromosome-linked recessive disorder that is predominantly male and rare in females, who are often carriers of the gene that causes the disease.
Causes
Causes
Pseudohypertrophic muscular dystrophy is caused by a mutation in the anti-myasthenic protein gene (DMD) on chromosome Xp21.
This mutation causes a deficiency of the anti-myasthenia gravis protein in the patient. This protein is located primarily in the cell membranes of skeletal and cardiac muscle and functions to support, resist pulling and tearing, and maintain cellular morphology. Deficiencies in this protein cause instability of the cell membrane, leading to necrosis and loss of function of the muscle cells, which in turn leads to generalized skeletal and cardiac muscle weakness.
In addition, this protein is also distributed in the cerebral cortex cells of patients with Duchenne muscular dystrophy (DMD), and its deficiency can cause mental retardation.
There is no definitive answer as to why the 2 types are formed. The more accepted theory is the reading frame principle. It simply means that if a mutation in the gene causes the anti-myasthenic protein to be short and non-functional, it will cause severe muscle cell instability, which is manifested as Duchenne-type muscular dystrophy (DMD), while if the gene abnormality is partially compensated for by a neighboring gene, the clinical symptoms will be milder, which is manifested as Becker-type muscular dystrophy (BMD).
Symptoms
Main Symptoms
Duchenne muscular dystrophy (DMD)
Muscle weakness
This patient has an early onset and is more severe, usually presenting with abnormal symptoms in early childhood.
Learning to walk is impaired, and when they do learn to walk, they walk very slowly, fall easily, and have difficulty getting back up after a fall.
Since the muscle lesions start around the hip joints, the patient walks with a swinging pelvis, anterior protrusion of the lower back and abdomen, and a backward tilt of the head and chest, as if he or she were a duck walking.
If you want to stand up while lying on your back, you need to roll over, kneel on both knees, support your feet with your hands, and leave the floor with your calves and thighs in turn, and finally straighten up.
As the condition worsens, the patient loses strength in the body and upper limbs, the arms cannot be raised, and the shoulder blades are elevated as if they were a pair of feathery wings.
Some patients will be unable to lie down on their backs due to weakness of the cervical muscles.
Pseudohypertrophy of muscles
In 90% of children, the muscles of several limbs will become abnormally thick, but with diminished strength.
The most common is the gastrocnemius (calf belly), followed by the deltoid, gluteus, and quadriceps (anterior thigh). (3) Bone and joint abnormalities
Limb contracture, atrophy, deformity, with the development of the disease can appear contracture of the Achilles tendon, the heel can not touch the ground, turned inward, like a horseshoe; elbows, knees, hips and other joints can not be normally straightened; scoliosis and other manifestations.
Systemic manifestations
In adolescence, children gradually lose their ability to walk, sit in wheelchairs, lie in beds, have shortness of breath, cough and fatigue.
Most of them also have panic attacks, shortness of breath, and fatigue.
A few children have some mental deficits, such as attention deficit and learning disabilities.
Most patients die before the age of 30 from respiratory infections and heart failure.
Becker type muscular dystrophy (BMD)
The clinical presentation of this type is similar to that of Duchenne-type muscular dystrophy (DMD).
The lesions first involve the hip and thigh muscles, manifesting as weakness of the thighs, and gradually spread to the shoulder muscles, manifesting as inability to raise and abduct the arms, in addition to pseudohypertrophy of the gastrocnemius muscle in a small number of patients.
Compared with Duchenne muscular dystrophy (DMD), patients with this type of disease start at a relatively late age, progress at a slower rate, and the disease is milder, and the patient’s intelligence is basically unaffected.
Complications
Patients with Duchenne muscular dystrophy (DMD) may suffer complications such as aspiration, sputum weakness, respiratory weakness, scoliosis, lung infections, respiratory failure, heart failure, and ultimately death due to the involvement of skeletal muscles and heart muscles throughout the body.
Sudden death may also occur in patients with Becker-type muscular dystrophy (BMD) due to cardiomyopathy, and the degree of myocardial damage does not parallel the degree of generalized skeletal muscle pathology.
Medical Care
Department of Medicine
Neurology
If symptoms such as limb weakness, abnormal gait, or abnormally thick calves occur, prompt medical attention is recommended. Pediatric patients may consult the Department of Pediatrics, especially the Department of Pediatric Neurology.
Preparation for medical treatment
Preparing for your visit: registering, preparing your documents, FAQs
Tips for seeking medical treatment
When visiting the doctor, try to describe the medical history, symptoms, family history, feeding situation, etc. as detailed and accurate as possible, and provide the doctor with video and photos of the patient.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there any slow walking, toeing on the ground, easy to fall, hobbling?
Are there symptoms of difficulty in walking up stairs and standing in a squatting position?
Are there any symptoms such as inability to raise both arms, inability to abduct over the head, difficulty in combing hair, washing face, dressing, etc.?
Are there any symptoms of scoliosis or inward turning of the feet?
Are there any signs of panic, chest tightness, shortness of breath, etc.?
List of medical history
How old was the patient when the onset of symptoms occurred?
Are there any family members with similar symptoms, patients diagnosed with the disease, or carriers of the gene that causes the disease?
Checklist
Test results from the last six months, which can be brought to the doctor’s office
Serum enzymatic tests: creatine kinase, lactate dehydrogenase, and creatine kinase isoenzymes, etc.
Imaging/acoustic imaging tests: muscle MRI, cranial MRI, echocardiography, etc.
Other tests: electromyography, electrocardiography, histology of muscle pathology, genetic testing, etc.
Medication list
Medication used in the last 3 months, if available in boxes or packages, bring with you to the doctor’s office
Prednisone, coenzyme Q10, vitamin D, etc.
Diagnosis
Diagnosis based on
medical history
Patient has a family history of similar symptoms, patients with this disease, or carriers of the causative gene.
Clinical manifestations
Symptoms
The symptoms often include limb weakness, difficulty in walking up stairs and standing in a squatting position, abnormal gait, abnormally thick calves, scoliosis, and inversion of the feet.
Physical signs
The doctor will check whether there are any abnormalities in muscle strength, muscle volume, muscle tone, nerve reflexes, etc. through physical examination.
Muscle strength is determined by the patient’s movements such as lifting arms and legs, walking and squatting.
Visual and tactile examination of changes in muscle volume to see if there is muscle atrophy and abnormal hypertrophy.
Feel the resistance when passively flexing and extending the patient’s joints to understand which parts of the muscle tone have changed.
Use the percussion hammer to strike the periosteum and tendons; use a blunt bamboo stick to gently stroke the plantar and dorsal parts of the foot to determine the site of the lesion and find out whether there are abnormal nerve reflexes.
Serum enzyme test
Purpose: To determine whether there is myocyte damage and to assist in the diagnosis of the disease.
Commonly used items: creatine kinase (CK), lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB).
Significance: CK reaches 20 to 100 times the normal value in patients with this disease.
Precautions: Fasting is not required for this test, but strenuous exercise should be avoided before the test.
Electromyography
Purpose: To assess the severity and progress of muscle injury.
Significance: This disease often has the typical manifestation of myogenic damage, which is manifested as short time limit of light contraction motor unit potential, low amplitude, polyphasic wave increase, etc., and vigorous contraction shows pathological interference phase.
Precautions:
The skin should be cleaned according to the doctor’s requirements before the examination.
There is a certain degree of pain during the examination, and it is necessary to try to relax and cooperate to complete the examination.
Pathologic histology
Purpose: To find out the lesions of muscle fibers and assist in diagnosis and differential diagnosis.
Significance: Fiber degeneration, necrosis, hypertrophy, hyperplasia, and a large number of adipose tissue and fibrous connective tissue hyperplasia, immunohistochemical staining can be seen in the anti-myocardial atrophy protein dystrophin expression decreased or missing.
Precautions:
This test is invasive, with some pain, and needs to be performed under local anesthesia when taking the biopsy specimen, and is usually performed when the genetic test fails to make a definitive diagnosis.
Keep the area clean and dry after the biopsy to avoid wound infection.
Genetic testing
Purpose: To discover the disease-causing genes, confirm the type of disease and determine the prognosis.
Significance: It can clarify the large segment deletion, duplication and point mutation of DMD gene.
Cautions:
It is not possible to classify Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) solely on the basis of genetic testing.
Family members of diagnosed patients should be screened for mutations in high-risk groups.
Imaging
Muscle magnetic resonance imaging (MRI)
MRI of the muscle reveals edema, fatty infiltration, and mesenchymal hyperplasia in the affected muscles, which appear to be “cannibalized. “Duchenne muscular dystrophy (DMD) begins with the gluteus maximus muscle and progresses to the posterior thigh muscles.
Precautions: Prior to the MRI examination, if you have any metal, pacemakers or stimulators in your body, you should inform your doctor in advance, and the doctor will decide whether the examination can be performed.
Echocardiography
Purpose of the test: It is mainly used to find out whether there are structural abnormalities in the heart, heart function, and to evaluate the prognosis.
It is common to see enlargement of the left ventricle, functional abnormalities, valvular insufficiency and other manifestations.
Precautions: Keep calm and wear loose-fitting clothes during the echocardiogram.
Other Tests
Electrocardiogram can assist in determining the degree of heart involvement.
Cardiopulmonary function test can understand the respiratory function and cardiopulmonary endurance.
Cranial MRI can assess the patient’s brain development and lesions
Intelligence Scale, Attention Deficit-Hyperactivity Disorder Assessment, Griffiths Scale of Mental Development, etc. can help determine the cognitive and psychological status of the patient.
Bone and joint examinations, including blood and urine calcium and phosphorus tests, bone age, bone density, and spinal X-rays, can help detect growth and developmental abnormalities and deformities.
Differential Diagnosis
Pseudohypertrophic myotonic dystrophy requires a differential between the two types and is often differentiated from limb-girdle muscular dystrophy (LGMD).
Table 1.Differentiation of several common types of muscular dystrophy
Main type DMDBMDLGMD
Patient sex male predominantly male predominantly both sexes
Patient gender
Male predominant
Male predominant
Both sexes
Age of onset before 5 years old5-15 years old during adolescence, with high variability
Age of onset
Before 5 years old
5 to 15 years old
Adolescence, high variability
Rate of progression Progression is rapid, often failing to go before 12 years of age Relatively slow Individual patient variability is large
Rate of progression
Progresses rapidly, often unable to walk by age 12 years
Relatively slow
Large individual patient variability
Primary site Pelvic girdle muscles, proximal limb Pelvic girdle muscles, proximal limb Pelvic girdle muscles, proximal limb Pelvic girdle muscles, proximal limb
Primary site
Pelvic girdle muscle, proximal limb
Pelvic girdle muscle, proximal limb
Pelvic girdle muscle, proximal limb
Muscle pseudohypertrophy is evident and may be mild or absent.
Pseudohypertrophy
Pseudohypertrophy
May be present
Mild or absent
Late myocardial damage is often present, often some types may be present.
Myocardial damage
Late stage often
Often
Some types may occur
Hypokinesia partially present rarely absent
Hypomelanosis
Partially present
Rare
None
Serum creatine kinase very high very high variously elevated
Serum creatine kinase
Very high
very high
Varying degrees of elevation
Treatment
Aims of treatment: There is no cure for this disease, the main purpose is to improve symptoms, improve quality of life and prolong life.
Treatment principle: The 2 types of treatment are similar and both are based on multidisciplinary management. In addition to drug treatment, rehabilitation and management of nutrition, respiration, spine bone and joint, growth and development are given at the same time.
Drug therapy
Gene therapy
Currently, it is mainly for patients with Duchenne-type muscular dystrophy (DMD).
It includes termination codon pass-through therapy, exon skipping therapy, exogenous tiny DMD gene replacement therapy, and gene repair therapy.
Although they can partially repair the expression of anti-myotonic proteins and improve symptoms, they do not achieve a cure for the disease.
Glucocorticoids
Commonly used drugs: prednisone, difcort.
The mechanism of drug action is not clear, and may be related to reducing the inflammatory response and contributing to the stabilization of myocyte membranes.
Precautions:
This type of drug used in this disease is a super-indication for the use of drugs, the doctor will be fully communicated with the patient and his family and signed informed consent before treatment.
Adverse reactions include obesity, hirsutism, acne, delayed growth and development, behavioral abnormalities, immunosuppression, blood pressure, blood sugar abnormalities, abdominal pain, vomiting, cataracts, osteoporosis, and infections.
It is important to take calcium, potassium and vitamin D supplements with the medication, and not to stop the medication abruptly on your own.
Other drugs
Coenzyme Q10 and Vitamin E may be useful in improving the patient’s muscle strength.
Medications such as captopril, irbesartan, propranolol, and digoxin may be used to improve heart rhythm, increase ejection, and improve heart function.
Drugs such as alendronate, vitamin D3, and calcium carbonate are often used to prevent and treat osteoporosis.
Surgery
When there are problems that severely affect the patient’s ability to exercise and quality of life, surgical options may be considered to improve symptoms.
Achilles tendon release can be performed in cases of Achilles tendon contracture to alleviate the symptoms of walking on the toes and not landing on the heel.
Posterior spinal fusion may be considered for severe scoliosis that affects cardiopulmonary function.
Those with severe atrioventricular block require pacemaker therapy, and those with dilated cardiomyopathy with heart failure may undergo heart transplantation.
Rehabilitation
Rehabilitation focuses on protecting weak muscles, slowing the progression of muscle weakness, preventing and minimizing progressive contractures and deformities, and maintaining ideal cardiopulmonary function.