muscular dystrophy-dystroglycanopathy

Muscular Dystrophy-Dystroglycanopathy: A Rare Inherited Disorder

Muscular dystrophy-dystroglycanopathy, also known as α-DG-related disorders, is a group of rare inherited neuromuscular disorders characterized by reduced glycosylation of α-dystroglycan (α-DG) [6]. This condition affects the muscle and nervous system, leading to severe structural brain and eye malformations, profound mental retardation, and congenital muscular dystrophy [5].

Types of Muscular Dystrophy-Dystroglycanopathy

There are several types of muscular dystrophy-dystroglycanopathy, including:

• Muscular dystrophy-dystroglycanopathy type A (MDDGA): This is an autosomal recessive disorder characterized by congenital muscular dystrophy with severe structural brain and eye malformations [8].
• Muscular dystrophy-dystroglycanopathy caused by mutations in the POMGNT1 gene: This type of muscular dystrophy-dystroglycanopathy is associated with characteristic brain and eye malformations, profound mental retardation, and congenital muscular dystrophy [4].

Symptoms and Characteristics

The symptoms of muscular dystrophy-dystroglycanopathy can vary depending on the specific type, but they often include:

• Congenital muscular dystrophy: Muscle weakness early in life
• Brain and eye malformations: Severe structural brain and eye anomalies
• Profound mental retardation: Intellectual disability
• Feeding difficulties: Hypotonia, joint contractures, and other musculoskeletal problems [3]

References

[1] - Not applicable (no relevant information found in search results 1) [2] - Not applicable (no relevant information found in search results 2) [3] - Symptoms can be present at birth or within the first two years of life, and may include muscle weakness, feeding difficulties, hypotonia, joint contractures and ... [context 3] [4] - An autosomal recessive muscular dystrophy caused by mutations in the POMGNT1 gene. It is associated with characteristic brain and eye malformations. [context 4] [5] - Muscular dystrophy-dystroglycanopathy type A, 10 is an autosomal recessive disorder characterized by brain and eye malformations, profound mental retardation, ... [context 5] [6] - α-Dystroglycanopathies are a group of rare inherited neuromuscular disorders characterized by reduced glycosylation of α-dystroglycan (α-DG). [context 6] [7] - An autosomal recessive muscular dystrophy caused by mutations in the POMT2 gene. It is associated with characteristic brain and eye malformations and profound ... [context 7] [8] - Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital ... [context 9]

Muscular dystrophy-dystroglycanopathy, also known as congenital muscular dystrophy due to dystroglycanopathy, is a rare genetic disorder characterized by severe muscle weakness, hypotonia (low muscle tone), and intellectual disability. The symptoms of this condition typically begin in early infancy.

Early Signs and Symptoms:

• Weak cry
• Difficulty feeding
• Weak muscle tone (hypotonia)
• Muscle weakness may improve, remain stable or worsen over time

Additional Symptoms:

• Feeding difficulties and breathing complications can develop in some cases
• Abnormally large globe
• Cataract
• Congenital ocular coloboma
• Joint and spinal deformities
• Respiratory insufficiency
• Decreased alpha-dystroglycan on immunohistochemical muscle biopsy

Developmental Delays:

• Persistent hypotonia (may be proximal or distal)
• Developmental delay, particularly motor and ambulation delay, but global delays are also common

It's essential to note that the symptoms of muscular dystrophy-dystroglycanopathy can vary significantly depending on the individual case. A specialist diagnosis is necessary for accurate identification and management of this condition.

References:

• [1] Weak cry, difficulty feeding, and weak muscle tone (hypotonia) are early signs and symptoms of muscular dystrophy-dystroglycanopathy ([9])
• Muscle weakness may improve, remain stable or worsen over time ([3])
• Feeding difficulties and breathing complications can develop in some cases ([3])
• Abnormally large globe, cataract, and congenital ocular coloboma are additional symptoms ([2], [6])
• Joint and spinal deformities, respiratory insufficiency, and decreased alpha-dystroglycan on immunohistochemical muscle biopsy are also associated with this condition ([4], [7])
• Persistent hypotonia and developmental delay are common in individuals with muscular dystrophy-dystroglycanopathy ([7])

Muscular dystrophy-dystroglycanopathy is a group of genetic disorders that affect muscle function and structure. Diagnostic tests for this condition are crucial in confirming the diagnosis and ruling out other potential causes of muscle weakness.

Common diagnostic tests for muscular dystrophy-dystroglycanopathy:

• Creatine kinase (CK) level: Elevated CK levels in the blood can indicate muscle damage, which is a hallmark of muscular dystrophies. [1]
• Muscle biopsy: A muscle biopsy involves taking a small sample of muscle tissue from the affected area for examination under a microscope. This test can help identify specific changes in muscle cells that are characteristic of certain types of muscular dystrophy-dystroglycanopathy. [4]
• Nerve conduction study (NCS) and electromyography (EMG): These tests measure the electrical activity of muscles and nerves, which can be abnormal in individuals with muscular dystrophies. [7]
• Brain MRI: In some cases, a brain MRI may be performed to rule out other conditions that can cause muscle weakness, such as structural abnormalities or neurological disorders.
• Genetic testing: Genetic testing can identify specific genetic mutations associated with muscular dystrophy-dystroglycanopathy. This test is particularly useful in confirming the diagnosis and providing information about the likelihood of passing the condition to offspring.

Other diagnostic tests:

• Multiplex ligation probe amplification (MLPA): This test can help identify deletions or duplications in specific genes associated with muscular dystrophy-dystroglycanopathy. [14]
• Array-based comparative genomic hybridization: This test can also help identify genetic abnormalities associated with muscular dystrophies.
• Free fetal DNA (ffDNA) testing: This is a non-invasive prenatal test that can detect certain genetic mutations associated with muscular dystrophy-dystroglycanopathy in the fetus. [9]

Importance of early diagnosis:

Early diagnosis and confirmation of muscular dystrophy-dystroglycanopathy are crucial for several reasons:

• Prognosis: Early diagnosis allows healthcare providers to provide accurate information about the prognosis and potential outcomes.
• Genetic counseling: Genetic testing can help identify genetic mutations associated with the condition, which is essential for providing accurate genetic counseling to families.
• Treatment planning: Early diagnosis enables healthcare providers to develop a treatment plan tailored to the individual's specific needs.

In conclusion, diagnostic tests for muscular dystrophy-dystroglycanopathy play a critical role in confirming the diagnosis and ruling out other potential causes of muscle weakness. A combination of clinical evaluation, laboratory tests, and genetic analysis can help provide an accurate diagnosis and inform treatment decisions.

Treatment Options for Muscular Dystrophy-Dystroglycanopathy

Muscular dystrophy-dystroglycanopathy is a group of genetic disorders characterized by muscle weakness and degeneration. While there is no cure, various treatment options can help manage the condition and improve quality of life.

• BBP-418 (Ribitol): This drug has been shown to be more effective than prednisone in treating dystroglycanopathy [1]. It works by targeting the underlying genetic mutations that cause the condition.
• Golodirsen (Vyondys 53): In 2019, the FDA approved golodirsen for treatment of some people with Duchenne muscular dystrophy who have a certain genetic mutation [2].
• Corticosteroids: Corticosteroid medicine, such as prednisone or deflazacort, has been shown to improve muscle strength and function in people with Duchenne MD [7]. However, the benefits are typically short-term (6 months to 2 years).
• Rapamycin: Four-week rapamycin treatment has been found to improve muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy [5] and in humans with Duchenne MD [6].
• Utrrophin therapy: The combination of drugs, dystrophin, and utrophin therapy may provide more options for future treatment of DMD [4].

Other Treatment Options

In addition to these specific treatments, other approaches can help manage muscular dystrophy-dystroglycanopathy:

• Heart medications: If the condition damages the heart, medications such as ACE inhibitors or beta blockers may be prescribed.
• Physical therapy and rehabilitation: Regular exercise and physical therapy can help maintain muscle strength and function.

References

[1] Luan J., Call J.A., Patel A., Peissig K.B., Fortunato M.J., Beedle A.M. Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy.

[2] FDA approval of golodirsen (Vyondys 53) for Duchenne muscular dystrophy.

[4] Combination therapy with drugs, dystrophin, and utrophin for DMD.

[5] Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy.

[6] Rapamycin treatment improves muscular dystrophy in humans with Duchenne MD.

[7] Corticosteroid medicine improves muscle strength and function in people with Duchenne MD.

The differential diagnosis for muscular dystrophy-dystroglycanopathy involves considering various conditions that present with similar symptoms.

Conditions to Consider

• Other dystroglycanopathies, such as DPM2-CDG (muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy) [1]
• Muscular dystrophies with brain and/or cognitive impairment, including Fukuyama congenital muscular dystrophy (FCMD) [2]
• Congenital myopathies, disorders of glycosylation, and limb-girdle muscular dystrophies [10]

Diagnostic Features

When differentiating between these conditions, it's essential to consider the following diagnostic features:

• Muscle weakness and wasting (atrophy)
• CNS migration disturbances in FCMD
• Cardiac involvement, such as dilated cardiomyopathy, which is also frequently observed in DMD and BMD [4]
• Severe epilepsy in DPM2-CDG

Diagnostic Tools

Available diagnostic tools for the various CMD subtypes include:

• Muscle MRI, which has been reported to be useful in differentiating between DGC-related muscular dystrophies [7]

It's crucial to consider these conditions and diagnostic features when making a differential diagnosis for muscular dystrophy-dystroglycanopathy.

References: [1] - Search result 3 [2] - Search result 2 [4] - Search result 4 [7] - Search result 7 [10] - Search result 10