Overview
Pseudohypertrophic progressive muscular dystrophy, also known as Duchenne muscular dystrophy (DMD), is a type of progressive muscular dystrophy that is an X-linked recessive disorder with a prevalence of about 1 in 3,500 live-born male infants. Females are mostly carriers of the causative gene, and onset of the disease is rare and mild. The disease is caused by mutations in the antimyotrophic protein gene (DMD gene), and is often characterized by progressive muscle atrophy and weakness with pseudohypertrophy of the gastrocnemius muscle and a duck gait. Currently, rehabilitation and medication to slow down the progression of the disease are the mainstays of treatment, and gene therapy to address the cause of the disease has entered the clinical trial stage.
Causes
Pseudohypertrophic progressive muscular dystrophy is caused by a mutation in the DMD gene located on the X chromosome and is an X-linked recessive disorder. the DMD gene is the largest gene found in humans, and encodes an anti-myasthenic protein that is an important component in stabilizing the membrane of the muscle cells. Its most important function is to maintain the stability of the muscle cell so that the muscle is not damaged during contraction. In patients, the lack of this protein in the muscle results in constant destruction and atrophy of the muscle since birth.
Symptoms
1. Progressive muscle weakness and regression of motor functions
After birth, the child’s activities such as lifting and sitting are normal during infancy. Difficulty in walking usually starts at the age of 3 to 5 years. The child is clumsy, prone to fall, walks shakily, and has difficulty in climbing stairs or getting up from sitting or lying down positions. Most of the children lose the ability to walk independently after 10 years old, and before 20 years old, most of them have weakness of throat muscles and respiratory muscles, low voice, difficulty in swallowing and breathing, and are prone to secondary infections such as aspiration pneumonia, which may be life-threatening.
2. Gowers sign
With the progression of the disease, the weakness of the gluteus medius muscle leads to a special duck step when walking, and the child needs to roll over to prone when getting up from the supine position, and then support the foot surface and the lower limbs with both hands to stand up slowly, which is called Gowers’ sign.
3. Pseudohypertrophy and generalized myasthenia gravis.
Pseudohypertrophy of bilateral gastrocnemius muscles due to fat and connective tissue hyperplasia occurs early in the child’s life, while the pelvic and thigh muscles gradually undergo progressive muscular atrophy, and the gastrocnemius muscle contrasts sharply with muscular atrophy in other parts of the body. With atrophy of the shoulder girdle muscles, the medial aspect of the scapula moves away from the chest wall when the arm is raised, creating a winged scapula. Spinal muscle atrophy can lead to spinal curvature deformities. Muscle contractures may occur in the later stages of the disease, resulting in flexion deformities of the knee, wrist, or elbow. Tendon reflexes are diminished or absent. The patient usually loses the ability to walk independently before the age of 12, and spends a lot of time in a wheelchair, and dies of respiratory failure and heart failure before the age of 20.
4. Other symptoms
Some patients have abnormal behavior and learning difficulties. 30% of patients have mental retardation.
Tests
1. Serum creatine kinase measurement
The level of creatine kinase (CK) in blood is significantly elevated, even up to 10,000 times the normal value. In the advanced stage of the disease, almost all muscle fibers have been degenerated and lost, and the serum CK level will drop to normal.
2. Electromyography
Electromyography shows myogenic damage, which may be accompanied by mild loss of innervation potentials and normal peripheral nerve conduction velocity.
3. Muscle biopsy
Muscle biopsy shows different degrees of degeneration, necrosis and regeneration of muscle fibers, accompanied by mononuclear cell infiltration and connective tissue proliferation. Further immunohistochemical staining to detect anti-myasthenia gravis protein, such as protein expression defects can also be used as a basis for diagnosis.
4.Genetic testing
Genetic testing is to detect the presence or absence of specific gene mutations by using multiplexed ligand probe amplification (MLPA) and second-generation sequencing, etc., which can provide the basis for diagnosis.
Diagnosis
According to the clinical manifestations and genetic pattern, especially the genetic test and anti-myasthenia gravis protein test, together with electromyography, muscle pathology examination and serum CK measurement, a definite diagnosis can usually be made.
1. The child has signs or symptoms such as difficulty in walking, Gowers’ sign, myasthenia gravis, and bilateral pseudohypertrophy of the gastrocnemius muscle.
2. Serum creatine kinase assay reveals a significant increase in concentration, with a decrease in late stages.
3. Electromyography reveals typical myogenic damage.
4. Muscle biopsy reveals myofibrillar degeneration, necrosis, and myotonic dystrophy-like pathological changes, which may be accompanied by mononuclear cell infiltration and connective tissue hyperplasia; absence of immunohistochemical staining may support the diagnosis.
5. Genetic testing can clarify the diagnosis of DMD gene mutation.
Differential diagnosis
Pseudohypertrophic progressive muscular dystrophy should be differentiated from spinal muscular atrophy type 3, inflammatory myopathies, metabolic myopathies and other diseases. It is mainly differentiated by muscle biopsy and genetic testing.
Complications
Scoliosis, respiratory infections, respiratory failure, heart failure, etc.
Treatment
1. Drug treatment
(1) Glucocorticoid therapy is the only drug that has been proven to be effective in slowing down the course of the disease. Short-term oral administration can enhance skeletal muscle strength and function, and may stabilize skeletal muscle strength and function over a longer period of time.
(2) Drugs such as Idebenone and Coenzyme Q10 help delay respiratory and cardiac muscle disease.
(3) L-arginine, branched-chain amino acids, creatine monohydrate and other drugs can promote muscle cell proliferation and metabolism, and can also be tried.
2. Gene therapy
Gene therapy can be used to treat the cause of the disease and is currently in the clinical trial stage.
3.Rehabilitation therapy
Reasonable and standardized rehabilitation therapy can help to improve the dysfunction caused by myasthenia gravis and improve the quality of life, and should be carried out early and standardized after diagnosis.
4. Surgical treatment
If there are deformities such as scoliosis and joint contracture, appropriate surgical methods can be chosen to correct them.
5.Supportive therapy
Supportive therapy mainly focuses on dyspnea and dysphagia to support and maintain the patient’s life. After respiratory muscle weakness and dyspnea, ventilator-assisted ventilation can be carried out; after dysphagia, nutritional support can be carried out through gastric tube and gastrostomy.
6.Psychological treatment
Pseudohypertrophic progressive muscular dystrophy can be a long-term problem for patients, bringing depression, low self-esteem and other psychological problems, which need timely counseling, and if necessary, psychological treatment.
Prognosis
The prognosis of this disease is poor. It is not only muscle dyskinesia, but also scoliosis, cognitive dysfunction, and multi-system diseases such as urinary system diseases, respiratory system diseases and heart diseases, and most of the patients die of respiratory and circulatory failure in early adulthood.
Prevention
1. Primary prevention
Pre-conception marriage guidance and genetic counseling, genetic diagnosis.
2. Secondary prevention
Prenatal screening to prevent birth defects.
3.Tertiary prevention
After the birth of newborns, CK test combined with molecular diagnostic technology to screen newborns for DMD, and provide early intervention and treatment for DMD patients.
Nursing care
1. Children may have motor disorders, and in severe cases, they cannot take care of themselves, so they need patient and careful care. Family members should pay attention to the difficulties in the child’s life and help him/her, and should not scold or humiliate him/her.
2. Under the guidance of a standardized neuromuscular disease rehabilitation therapist, passive movement of joints can be helped to maintain muscle function and prevent joint contracture.