congenital muscular dystrophy due to integrin alpha-7 deficiency

Congenital Muscular Dystrophy Due to Integrin Alpha-7 Deficiency

Congenital muscular dystrophy due to integrin alpha-7 deficiency is a rare genetic disorder that affects the development and function of skeletal muscle. This condition is characterized by early motor development delay, muscle weakness, and mild elevation of serum creatine kinase levels.

Key Features:

• Early motor development delay [1]
• Muscle weakness with mild elevation of serum creatine kinase levels [2][4][5][10]
• Progressive disease course with predominantly proximal muscle weakness and atrophy [3][4][10]
• Motor development regress [4][10]
• Scoliosis [6][10]
• Respiratory insufficiency [6][10]

Causes:

This condition is caused by mutations in the integrin-alpha 7 gene, leading to a deficiency of the protein. This deficiency affects the extracellular matrix and disrupts muscle development and function.

References:

[1] Congenital muscular dystrophy with integrin alpha-7 deficiency is characterized by early motor development delay [4] [2] Muscle weakness with mild elevation of serum creatine kinase levels [2][4][5][10] [3] Progressive disease course with predominantly proximal muscle weakness and atrophy [3][4][10] [4] Congenital muscular dystrophy due to integrin alpha-7 deficiency is a rare genetic congenital muscular dystrophy due to extracellular matrix protein anomaly [1][2][4][5] [5] Early motor development delay and muscle weakness with mild elevation of serum creatine kinase that may be followed by progressive disease course with predominantly proximal muscle weakness and atrophy, motor development regress, scoliosis and respiratory insufficiency [10] [6] This form of congenital muscular dystrophy is characterized by neonatal hypotonia, proximal muscle weakness and atrophy, delayed motor development, cognitive impairment, scoliosis, dyspnea due to respiratory muscle weakness, mildly increased CK levels, and dystrophic changes in muscle biopsy with lack of integrin-alpha-7 staining [6] [10] Congenital muscular dystrophy with integrin alpha-7 deficiency is a rare, genetic, congenital muscular dystrophy due to extracellular matrix protein anomaly characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase that may be followed by progressive disease course with predominantly proximal muscle weakness and atrophy, motor development regress, scoliosis and respiratory insufficiency [10]

Early Signs and Symptoms

Congenital muscular dystrophy due to integrin alpha-7 deficiency is characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase. This may be followed by a progressive disease course with predominantly proximal muscle weakness and atrophy, motor development regression, scoliosis, and respiratory insufficiency [1][2][10].

Clinical Features

The clinical features of this condition include:

• Fatty replacement of skeletal muscle
• Gowers sign
• Hypotonia (low muscle tone)
• Increased variability in muscle fiber diameter
• Muscle weakness
• Muscular atrophy

These symptoms typically present at birth or within the first few months of life [8][9].

Progressive Disease Course

As the disease progresses, patients may experience:

• Proximal muscle weakness and atrophy
• Motor development regression
• Scoliosis (abnormal curvature of the spine)
• Respiratory insufficiency

These symptoms can lead to significant morbidity and mortality if left untreated [5][11].

References

[1] Congenital muscular dystrophy with integrin alpha-7 deficiency is a rare, genetic, congenital muscular dystrophy due to extracellular matrix protein anomaly characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase...

[2] ...that may be followed by progressive disease course with predominantly proximal muscle weakness and atrophy, motor development regression, scoliosis and respiratory insufficiency.

[5] In a review of congenital muscular dystrophies, Reed (2009) stated that the phenotype associated with ITGA7 deficiency is better characterized as a 'muscular dystrophy' than a 'myopathy' since knockout mice show clinical and histopathologic features of a progressive muscular dystrophy (Mayer et al., 1997).

[8] A form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint...

[9] Jul 3, 2019 — Muscle biopsy shows signs of dystrophy, including a marked increase in endomysial and perimysial connective tissue; variability in fiber size...

[10] Congenital muscular dystrophy with integrin alpha-7 deficiency is a rare, genetic, congenital muscular dystrophy due to extracellular matrix protein anomaly characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase, that may be followed by progressive disease course with predominantly proximal muscle weakness and atrophy, motor development...

[11] Disease definition. Congenital muscular dystrophy with integrin alpha-7 deficiency is a rare, genetic, congenital muscular dystrophy due to extracellular matrix protein anomaly characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase, that may be followed by progressive disease course with...

Diagnostic Tests for Congenital Muscular Dystrophy Due to Integrin Alpha-7 Deficiency

The diagnostic tests for congenital muscular dystrophy due to integrin alpha-7 deficiency are crucial in identifying the genetic basis of this rare condition. According to search results [8], the most important diagnostic tools include:

• CK level: A blood test that measures creatine kinase (CK) levels, which can be mildly elevated in individuals with this condition.
• Nerve conduction study: An electrical test that evaluates nerve function and can help identify muscle weakness or atrophy.
• EMG with or without repetitive nerve stimulation: An electromyogram (EMG) test that measures the electrical activity of muscles and can help diagnose muscle damage or dysfunction.
• Brain MRI: A magnetic resonance imaging (MRI) scan that examines brain structure and function, which can be affected in individuals with this condition.
• Muscle biopsy: A surgical procedure that involves taking a small sample of muscle tissue for examination under a microscope.

These diagnostic tests are essential in confirming the diagnosis of congenital muscular dystrophy due to integrin alpha-7 deficiency [9]. Additionally, genetic testing is recommended to identify mutations in the ITGA7 gene, which can inform prognosis and clinical management [7].

References:

• Search result 8
• Search result 9

Current Status of Drug Treatment

There is currently no specific treatment or cure for congenital muscular dystrophy (CMD) due to integrin alpha-7 deficiency [1, 9]. However, researchers have been exploring various therapeutic options to manage the condition.

• Alisporivir: A study published in 2023 found that alisporivir was effective in treating muscular dystrophy in mice models with integrin alpha-7 deficiency [3]. This drug showed promise in improving muscle function and reducing symptoms.
• Laminin-111 treatment: Research has also shown that laminin-111, a protein component of the extracellular matrix, can improve muscle regeneration in mice with integrin alpha-7 deficiency [6].
• Supportive care: Aggressive supportive care is essential to preserve muscle function and overall health in individuals with CMD due to integrin alpha-7 deficiency [5]. This may include physical therapy, respiratory support, and other interventions to manage symptoms.

Potential Therapeutic Targets

While there are no approved treatments for CMD due to integrin alpha-7 deficiency, researchers have identified potential therapeutic targets. These include:

• Alpha 7 beta 1 integrin: Studies suggest that the alpha 7 beta 1 integrin may play a critical role in muscle repair and regeneration [7].
• Muscle stem cells: Targeting muscle stem cells may also be an effective approach to treating CMD due to integrin alpha-7 deficiency.

Future Directions

Further research is needed to develop effective treatments for CMD due to integrin alpha-7 deficiency. Ongoing studies are exploring new therapeutic strategies, including gene therapy and small molecule therapies [9].

References:

[1] Context result 4 [3] Context result 3 [5] Context result 5 [6] Context result 6 [7] Context result 7 [9] Context result 9

Differential Diagnosis of Congenital Muscular Dystrophy due to Integrin Alpha-7 Deficiency

Congenital muscular dystrophy (CMD) caused by integrin alpha-7 deficiency is a rare genetic disorder characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase. The differential diagnosis of this condition involves considering various other congenital myopathies and muscular dystrophies that may present with similar symptoms.

Key Features to Consider:

• Early motor development delay: Individuals with integrin alpha-7 deficiency often experience delayed motor milestones, which can be a key feature in differentiating this condition from other CMDs.
• Muscle weakness and atrophy: Proximal muscle weakness and atrophy are common features of integrin alpha-7 deficiency, which can help distinguish it from other muscular dystrophies.
• Mild elevation of serum creatine kinase: A mildly increased CK level is often observed in individuals with integrin alpha-7 deficiency, which can aid in the differential diagnosis.

Other Conditions to Consider:

• Congenital myopathies: These are a group of disorders characterized by muscle weakness and atrophy, but they typically do not progress as rapidly as muscular dystrophies.
• Muscular dystrophies: Other forms of muscular dystrophy, such as Duchenne and Becker muscular dystrophy, can present with similar symptoms to integrin alpha-7 deficiency.

Diagnostic Features:

• Muscle biopsy: A muscle biopsy is essential for diagnosing integrin alpha-7 deficiency. The biopsy typically shows dystrophic changes in the muscle tissue, including lack of integrin-alpha-7 staining.
• Genetic testing: Genetic testing can confirm the presence of mutations in the ITGA7 gene, which is responsible for integrin alpha-7 deficiency.

References:

• [1] Guo et al. (2006) - Human patients suffering from a congenital myopathy with delayed motor milestones have subsequently been identified due to primary integrin α7 deficiency.
• [2] Bertini et al. (2011) - Overall differential diagnosis of CMD has to take into account congenital myopathies, ie, myopathies with typical structural or ultrastructural features on the muscle biopsy.
• [3] Topaloğlu et al. (2024) - The phenotype is variable, and the disease is characterized by mild muscle weakness, motor development delay, and mildly increased CK levels.

Note: The references provided are based on the search results within the context.