What Is Actin-Accumulation Myopathy?
Actin-accumulation myopathy is a rare genetic disorder caused by the aggregation of actin filaments. The actin filaments are minute components of the cytoskeleton. They form the internal protein skeleton of the cell and are responsible for various functions such as support, shape, structure, adhesion, and muscle contraction. These filaments can only be seen under a microscope. This condition mainly affects the muscles that are necessary for body movements. The characteristic features of this condition include severe weakness of the body muscles called myopathy and poor muscle tone called hypotonia. This condition becomes evident in early childhood, so the affected infants may face issues with feeding and swallowing, difficulty controlling head movements, and a whimpering cry. Affected infants may also develop respiratory distress due to the severe weakness of their respiratory muscles and may even require artificial ventilation.
Affected individuals' breathing will mostly be too shallow or too slow, called hypoventilation and mainly seen during sleep. This can lead to an oxygen supply shortage and carbon dioxide accumulation in the blood, which can lead to frequent respiratory infections and even life-threatening complications. In some rare cases, the affected individuals also have impaired heart muscle function, called cardiomyopathy. Because of respiratory and cardiac problems, most affected infants do not survive for long periods. Very few individuals survive. However, they will have developmental delays due to impaired motor skills such as crawling, sitting, standing, and walking.
What Are the Causes of Actin-Accumulation Myopathy?
Actin-accumulation myopathy is mainly caused by ACTA1 (Actin Alpha 1) gene changes. However, in some infants with actin-accumulation myopathy, no mutation in the ACTA1 gene has been reported, so the exact cause of the disorder in these infants is unclear. This gene provides directions for producing skeletal alpha (α)-actin protein. This gene is a member of the actin protein family in skeletal muscles. They play a key role in cell structure, motility, and integrity. Alpha, beta, and gamma actin isoforms are responsible for the contractile apparatus, but alpha actins are a major constituent. Beta and gamma actins help regulate cell motility. Actin molecules are present in the thin filaments of muscle fiber, and another protein called myosin is present in the thick filaments of the muscle filaments, which are both main components of muscle contraction. The way the thick and thin filaments bind and release allows the muscle to move so the muscles can contract.
The leading cause of actin-accumulation myopathy is due to ACTA1 gene mutations. The gene mutation affects how the skeletal α-actin protein binds to ATP (Adenosine Triphosphate). ATP is an essential component in forming thin filaments from each actin molecule. If there are abnormalities in actin-ATP binding, then abnormal thin filament formation may occur, and muscle contraction may be impaired, leading to the signs and symptoms of actin-accumulation myopathy, such as muscle weakness. Actin-accumulation myopathy occurs in an autosomal dominant pattern. This means one copy of the mutated gene in each cell is enough to cause this condition. Many cases are not passed down from the family; they occur as de novo mutations in the gene, meaning the mutation happens spontaneously during DNA (deoxyribonucleic acid) replication during cell division, so no family history of this disorder would have been reported in the family.
What Are the Symptoms of Actin-Accumulation Myopathy?
The symptoms of actin-accumulation myopathy may vary depending on the severity of the condition. This condition may be present at birth or may develop during early childhood.
The common signs and symptoms of this condition may include:
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Myopathy: Myopathy means muscle weakness. Generally, proximal muscles, such as those in the shoulders, thigh, and hips, are affected, so the child may face difficulty lifting objects or climbing stairs. In some cases, generalized muscle weakness can be noted. In most cases, prominent facial weakness with or without upper eyelid drooping is also reported.
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Fatigue: Infants with actin-accumulation myopathy may experience fatigue even with minimal physical activity due to muscle weakness. So they may always be cranky and cry.
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Delayed Motor Milestones: Children with this condition may experience delays in their developmental milestones, such as crawling, sitting, standing, and walking.
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Respiratory Difficulties: Individuals with this condition may also have breathing difficulties due to impaired respiratory muscles. Generally, affected infants will have hypoventilation, especially during sleep. In some severe cases, breathing will be tough and may require ventilation, and even this condition can cause life-threatening complications.
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Orthopedic Complications: Orthopedic complications like spinal rigidity, early fixed kyphoscoliosis (excessive forward curve of your spine), congenital hip dislocation, and permanent tightening of joints or tendons may develop in individuals.
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Cardiac Complication: In some rare cases, cardiomyopathy has been reported, which can lead to life-threatening complications.
How Is Actin-Accumulation Myopathy Diagnosed?
Actin accumulation myopathy is a very rare condition, so the diagnosis of this condition is very challenging. The healthcare professionals may complete a clinical evaluation, including the patient's medical history, physical examination, and family history of neuromuscular disorders.
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Physical Examination: A neurological examination will be carried out to check for muscle strength, reflexes, and coordination.
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Muscle Biopsy: A muscle biopsy may be done on characteristic features of muscle tissue, such as actin filament accumulation.
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Genetic Testing: If any abnormalities are detected in muscle biopsy, genetic testing is done to check for mutations in ACTA1 genes associated with AAM. This will confirm the disease condition.
What Is the Treatment for Actin-Accumulation Myopathy?
There is no cure for actin-accumulation myopathy, and the main aim of the treatment is to manage the presenting illness and improve quality of life.
Treatment options may include:
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Physical Therapy: Physical therapy helps improve muscle strength, mobility, and flexibility and prevents joint contractures.
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Occupational Therapy: Occupational therapy can help to improve daily activities and functional independence.
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Respiratory Support: Respiratory support is necessary for individuals with respiratory muscle impairment to help them with breathing.
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Medications: Depending on the presenting illnesses and complications, medications may be required to relieve pain and improve the patient's immunity.
Conclusion:
Actin accumulation myopathy is a rare genetic disorder due to the abnormal accumulation of actin filaments within muscle cells. A mutation in the ACTA1 gene causes it. The characteristic features of this disorder include myopathy, developmental delays, orthopedic disorders, respiratory issues, and, in rare cases, cardiomyopathy. The prognosis for this condition is bad due to the involvement of respiratory and cardiac muscles. Treatment mainly focuses on managing the symptoms and improving the quality of life.
