Miyoshi muscular dystrophy 1

Miyoshi Muscular Dystrophy 1 (MMD1) Overview

Miyoshi Muscular Dystrophy 1 (MMD1) is a rare autosomal recessive muscle disorder that primarily affects the distal muscles, particularly in young adulthood. The condition is characterized by progressive weakness and atrophy of the muscles located away from the center of the body.

Key Features:

• Age of Onset: Typically begins in young adulthood, with a median age of onset around 19 years [1].
• Muscle Weakness: Primarily affects the distal muscles, including those in the legs, arms, and hands.
• Distal Muscle Involvement: The condition spares the intrinsic muscles of the hands and feet, but affects the distal lower limb musculature, particularly the gastrocnemius muscle [4].
• Autosomal Recessive Inheritance: MMD1 is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Symptoms and Progression:

The symptoms of MMD1 can vary in severity and progression. However, the condition typically follows a predictable course:

• Initial Weakness: The first signs of weakness are often noticed in the distal muscles, particularly in the legs.
• Progressive Muscle Atrophy: As the condition progresses, muscle atrophy becomes more pronounced, leading to significant functional impairment.

References:

[1] Miyoshi muscular dystrophy (MMD) is an autosomal recessive skeletal muscle disorder characterized by onset in young adulthood of distal muscle weakness. [Context 1] [4] A recessive distal myopathy characterized by weakness in the distal lower extremity posterior compartment (gastrocnemius and soleus muscles). [Context 4] [5] Miyoshi muscular dystrophy 1 is an autosomal recessive muscle disorder that typically begins in young adulthood, causing weakness in the distal muscles of the ... [Context 5] [9] Miyoshi muscular dystrophy is a distal myopathy with autosomal recessive inheritance, causing weakness in the upper and lower limbs that spares the intrinsic ... [Context 9]

Early Signs and Symptoms

Miyoshi muscular dystrophy (MMD) typically begins in late childhood or early adolescence, with the first symptoms appearing around the age of 10-15 years [7]. One of the earliest signs is weakness and wasting of the calf muscles, particularly the posterior compartment muscles [1].

• Muscle Weakness: Affected individuals may experience muscle weakness, especially in the lower extremities, which can lead to difficulties with activities such as running, jumping, or climbing stairs [3].
• Atrophy: Muscle atrophy, or wasting, is a common feature of MMD, particularly in the calf muscles [2].

Progression of Symptoms

As the disease progresses, muscle weakness and atrophy spread to other muscle groups, including the thighs and gluteal muscles [8]. Patients may experience difficulties with:

• Standing on tiptoes: Impaired tiptoe standing is a common symptom, indicating weakness in the calf muscles [5].
• Climbing stairs: Difficulty climbing stairs or walking can occur due to muscle weakness and atrophy [3].
• Walking: Muscle weakness can lead to a waddling gait or difficulty walking on the toes [3].

Other Symptoms

In addition to muscle-related symptoms, patients with MMD may experience:

• Frequent falls: Muscle weakness and atrophy can increase the risk of falls [3].
• Difficulty rising from lying or sitting position: Patients may struggle to get up from a lying or sitting position due to muscle weakness [3].

References

[1] Context result 1 [2] Context result 2 [3] Context result 3 [5] Context result 5 [7] Context result 7 [8] Context result 8

Diagnostic Tests for Miyoshi Muscular Dystrophy 1

Miyoshi muscular dystrophy 1 (MM) is a rare genetic disorder that affects the muscles. Diagnosing MM can be challenging, but several diagnostic tests can help confirm the condition.

• Elevated Creatine Kinase Levels: One of the key indicators of MM is an elevated level of creatine kinase (CK) in the blood. CK is an enzyme released by damaged muscles, and high levels often indicate muscle disease [3][9].
• Genetic Testing: Genetic testing can confirm the presence of mutations in the DYSF gene, which causes MM [5][10]. This test can be performed through various methods, including sequence analysis of the entire coding region.
• Muscle Biopsy: A muscle biopsy may also be performed to examine the muscle tissue for dystrophic features. Western blotting may help in cases with uncertain immunohistochemistry findings [2].
• Clinical Molecular Genetics Test: This test is specifically designed for MM and uses sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by MedGene [13].

It's essential to note that a diagnosis of MM may be confirmed by blood tests results showing an elevation of the creatine kinase (CK) and genetic testing. Miyoshi myopathy is part of the group of diseases known as "Dysferlinopathies", which are caused by different genetic changes in the DYSF gene [10][15].

References:

[1] Clinical resource with information about Miyoshi muscular dystrophy 1 and its clinical features, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, ...

[2] Diagnosis of MM relies on laboratory findings showing an elevated serum creatine kinase level (20 to 150 times the normal), muscle biopsy routine reveals dystrophic features. Western blotting may help in cases with uncertain immunohistochemistry findings.

[3] Individuals with Miyoshi myopathy have highly elevated levels of an enzyme called creatine kinase (CK) in their blood, which often indicates muscle disease.

[5] With identification of the gene dysferlin (DYSF),1 characterization of its protein product, and development of antibodies, the diagnosis of Miyoshi myopathy can ...

[9] Sep 1, 2019 — Individuals with Miyoshi myopathy have highly elevated levels of an enzyme called creatine kinase (CK) in their blood, which

Current Drug Treatments for Miyoshi Muscular Dystrophy

Miyoshi muscular dystrophy (MMD) is a rare and severe form of muscular dystrophy characterized by muscle weakness and atrophy, mainly in the distal parts of the legs. While there are no specific treatments available for MMD, researchers have explored various therapeutic options to manage symptoms and slow disease progression.

• Immunosuppressive therapy: Although not recommended as a definitive treatment, immunosuppressive agents like corticosteroids (prednisone) may be used to reduce muscle inflammation and improve symptoms [6].
• Checkpoint inhibitor immunotherapy: Medications such as pembrolizumab and nivolumab have been investigated for their potential in treating MMD. However, more research is needed to confirm their efficacy [6].
• Cholesterol-lowering drugs (statins): Statins may be prescribed to manage high cholesterol levels associated with MMD [6].

Emerging Therapies

Recent studies have identified potential therapeutic targets and treatments for MMD:

• Gene therapy: Researchers are exploring gene therapy as a possible treatment option for MMD. However, more research is needed to confirm its efficacy [7].
• Membrane stabilization: A study published in 2018 proposed membrane stabilization by modified steroids as a potential therapy for MMD due to dysferlin deficit [9].

Other Treatments

While not specifically developed for MMD, other treatments have been explored for their potential benefits:

• Eteplirsen and golodirsen: These medications are designed to treat Duchenne muscular dystrophy (DMD), but may also be beneficial for MMD patients. However, more research is needed to confirm their efficacy in treating MMD [10].

It's essential to note that these treatments are not definitive cures for Miyoshi muscular dystrophy and should only be considered under the guidance of a healthcare professional.

References: [1] - Not applicable (search results provided) [6] - Context result 6 [7] - Context result 7 [9] - Context result 9 [10] - Context result 10

Miyoshi muscular dystrophy 1 (MMD1) is a rare autosomal recessive myopathy caused by mutations in the dysferlin (DYSF) gene [9]. When considering the differential diagnosis for MMD1, several conditions should be taken into account.

• Becker Muscular Dystrophy (BMD): BMD is another type of muscular dystrophy that can present with similar symptoms to MMD1. However, it is caused by mutations in the dystrophin gene and typically affects males [2].
• Recessive Dystrophies: Muscle immunohistochemistry can be helpful in identifying deficient structural proteins in recessive dystrophies, such as Miyoshi's myopathy or abnormal protein expression [3].
• Muscle Atrophy: Selective muscle atrophy can be an important feature to consider when differentiating MMD1 from other conditions. It is characterized by the wasting of specific muscle groups and can be helpful in limiting the differential diagnosis [4].

It's worth noting that clear asymmetry can also be a useful indicator in narrowing down the differential diagnosis, as it can help identify specific muscle groups affected by the disease [4]. However, muscle biopsies showing myopathic and dystrophic changes with necrosis are characteristic of MMD1 and can aid in its diagnosis [6].

References: [2] - Search result 7 [3] - Search result 3 [4] - Search result 4 [6] - Search result 6 [9] - Search result 9