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Infantile myofibrillar myopathy (MFM)

Infantile myofibrillar myopathy (MFM)



Overview

Infantile myofibrillar myopathy (MFM) is a severe, inherited muscle disorder that appears in the first weeks of life, leading to rapid progression of muscle weakness, stiffness, and respiratory failure, often resulting in death within the first six months. It is characterized by the breakdown of muscle fibers (myofibrils) in both skeletal and cardiac muscles, and can also involve heart problems. This condition can be caused by mutations in genes like CRYAB, which provides instructions for making the αB-crystallin protein. 

Symptoms

Early infancy symptoms

Weak crying

Sleep apnea

Recurrent respiratory tract infections

Progressive stiffness of the trunk, abdomen, and limbs 

Other common symptoms

Muscle weakness, especially affecting breathing and movement

Fatigue

Cardiomyopathy (weakened heart muscle), which may be the first symptom

Muscle pain (myalgia)

Loss of sensation in the limbs (peripheral neuropathy)

Skeletal problems like joint stiffness (contractures) or scoliosis (abnormal spine curvature)

Eye problems, such as cataracts 

Causes

Mutations in the CRYAB gene 

Inheritance pattern: It is an autosomal recessive disorder, meaning an affected infant inherits two copies of the mutated CRYAB gene, one from each parent.

Symptoms: The condition typically presents in the first few weeks of life with progressive muscle stiffness (particularly in the trunk and limbs), difficulty breathing, and a poor prognosis with a high risk of early death.

Genetic mechanism: The mutations result in a non-functional or improperly functioning αB-crystallin protein, which is essential for muscle fiber structure. 

Other genetic causes

BAG3-related MFM: In some cases, mutations in the BAG3 gene can also cause an infantile onset of MFM.

DES-related MFM: Mutations in the DES gene can be another cause, with some patients having an infantile disease onset. 

General mechanism of MFM

Z-disk weakening: Regardless of the specific gene involved, MFM is fundamentally caused by a defect in the Z-disk, a crucial part of the muscle fiber.

Protein aggregation: The mutations lead to the accumulation of faulty proteins, weakening the Z-disk and causing the muscle fibers to degenerate over time. 

Diagnosis

Clinical evaluation: A doctor will assess the infant's symptoms, which often include profound muscle weakness, difficulty breathing, and feeding issues.

Electromyography (EMG): This test helps identify non-specific myopathic findings, abnormal electrical activity, and sometimes myotonic discharges.

Muscle biopsy: A muscle biopsy is a key diagnostic tool. It will reveal myofibrillar disorganization, accumulation of abnormal proteins, and a characteristic appearance of deposits in the muscle fibers.

Molecular genetic testing: This can confirm the diagnosis by finding mutations in genes associated with myofibrillar myopathy, such as DES, CRYAB, MYOT, ZASP, FLNC, and others.

Imaging studies:

MRI: A whole-body MRI or Myo-MRI can identify specific patterns of muscle involvement, such as fatty infiltration in certain muscles.

Cardiac screening: Due to the risk of cardiomyopathy, a yearly cardiac screening including electrocardiography (ECG) and echocardiography is recommended. 

Treatment

Symptomatic and supportive treatments

Physical and occupational therapy: These therapies are crucial for maintaining muscle function and independence in daily activities.

Breathing support: If respiratory muscles are weak, support can range from non-invasive methods like CPAP or BiPAP machines to more invasive options like a surgical incision for a breathing tube.

Cardiac management: If the heart muscle is affected, regular monitoring is necessary. Interventions like a pacemaker or ICD may be needed for heart rhythm problems, and in severe cases, a heart transplant could be a consideration. 

Emerging and research-based treatments

Metformin: Studies have shown that the drug metformin can help reduce fiber disintegration and improve muscle function in certain types of myofibrillar myopathy, according to the National Institutes of Health (NIH) and News-Medical.net.

Gene therapy: This is a potential future treatment for some congenital myopathies, though it is still under investigation for myofibrillar myopathy.

Targeted medications: Medications that target calcium and myosin regulation are being explored in research settings. 

Type of Doctor Department : A rheumatologists

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