autosomal dominant centronuclear myopathy

Autosomal dominant centronuclear myopathy (AD-CNM) is a rare, inherited condition that affects the muscles. It is characterized by an abnormality in which the nuclei are located in the center of the muscle fibers, rather than at the periphery.

Key Features:

• Inheritance Pattern: AD-CNM is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder.
• Muscle Weakness: The condition is characterized by progressive muscle weakness ranging from mild to profound.
• Variable Severity: The severity of the condition and associated signs and symptoms vary significantly among affected people.
• Age of Onset: The age of onset can range from adolescence to young adulthood, although earlier and later presentations have been reported.

Other Forms:

• X-linked Myotubular Myopathy
• Autosomal Recessive Centronuclear myopathy

Note that the cause of the condition and associated signs and symptoms vary by subtype.

Autosomal dominant centronuclear myopathy (AD-CNM) is a rare, inherited condition that affects the muscles. The specific signs and symptoms can vary greatly among affected individuals.

Common Signs and Symptoms:

• Muscle weakness, particularly in the distal muscles of the arms and legs [1]
• Hypotonia, or low muscle tone, which can be apparent from birth [3][5]
• Delayed motor milestones, such as sitting, standing, and walking [5]
• Facial weakness and ptosis (drooping eyelids) [4][5]
• Rib cage deformities, which can sometimes lead to respiratory insufficiency [3]

Variability in Severity:

It's essential to note that the severity of AD-CNM can vary significantly among affected individuals. Some people may experience only mild symptoms, while others may develop more severe complications, including life-threatening respiratory issues.

References:

• [1] Jungbluth H, Laporte J, Wallgren-Pettersson C. Autosomal dominant centronuclear myopathy. Orphanet...
• [3] Disease definition. A rare, autosomal dominant congenital myopathy characterized by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy (hypotonia, distal/proximal muscle weakness, rib cage deformities (sometimes associated with respiratory insufficiency), ptosis, ophthalmoparesis and weakness of the muscles of facial expression with dysmorphic...
• [4] Autosomal Centronuclear Myopathy is generally accepted as less severe than X-linked myotubular myopathy, but certain mutations can cause life-limiting symptoms such as early respiratory failure. Latest research shows that 63% of people with congenital titinopathy have respiratory insufficiency and some require the use of ventilators.
• [5] Other common signs and symptoms include delayed motor milestones, facial weakness and ptosis. Etiology. Centronuclear myopathies (CNMs) ... (Xq28), encoding myotubularin 1 (X-linked centronuclear myopathy), autosomal-dominant mutations in DNM2( 19p13.2), encoding dynamin-2, autosomal dominant or recessive mutations in BIN1...

Autosomal dominant centronuclear myopathy (AD-CNM) can be diagnosed through various diagnostic tests, including:

• Molecular genetic testing: This test is available as a diagnostic service at specialized laboratories and can identify mutations in the DNM2 gene, which is associated with AD-CNM [2]. The mutation spectrum in the large GTPase dynamin 2 has been studied, and genotyping-phenotype correlation has been established [2].
• Muscle biopsy: A muscle biopsy can show typical histological findings of central nuclei, hypotrophy, and predominance of type I fibers, which are characteristic of AD-CNM [7]. Differential diagnosis is also possible through muscle biopsy.
• Exome-based NextGen sequencing with CNV analysis: This testing approach is recommended for identifying a potential genetic basis for the condition and can inform prognosis [9].
• Muscle ultrasound and magnetic resonance imaging (MRI): These imaging techniques have been increasingly used to differentiate between different forms of congenital myopathies, including AD-CNM [8].

It's worth noting that diagnosis of AD-CNM is highly dependent on interpretation of muscle biopsy findings, and recent testing of panels of disease genes using massive NGS approaches has given different findings [12]. A definitive diagnosis can be made through a combination of these diagnostic tests.

References:

[2] Dechene ET, et al. Mutation spectrum in the large GTPase dynamin 2, and genotyping-phenotype correlation in autosomal dominant centronuclear myopathy. Hum Mutat. 2012;33:949-959. [7] Diagnosis is based on typical histological findings of central nuclei, hypotrophy and predominance of type I fibers. Differential diagnosis. The main... [8] by KN North · 2014 · Cited by 338 — Over recent years muscle ultrasound and magnetic resonance imaging (MRI) have been increasingly used to differentiate between different forms of congenital ... [9] Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. [12] Autosomal dominant centronuclear myopathy is classically associated with mutations in DNM2 ... a definitive diagnosis. Recent testing of panels of disease genes using massive NGS approaches has given different findings. In particular, it has been emphasized that the diagnosis of congenital myopathy is highly dependent on interpretation of...

Current Treatment Options for Autosomal Dominant Centronuclear Myopathy

Unfortunately, there is no specific therapy or cure available for autosomal dominant centronuclear myopathy (AD-CNM). However, treatment options are focused on managing the symptoms and improving quality of life.

• Symptom management: The primary goal of treatment is to alleviate the symptoms associated with AD-CNM, such as muscle weakness, fatigue, and respiratory insufficiency. This may involve a multidisciplinary approach, including physical therapy, occupational therapy, and respiratory care.
• Drugs for symptom relief: While there are no specific drugs approved for treating AD-CNM, some medications may be used to manage symptoms. For example:
  • Salbutamol (a bronchodilator) may be used to help with breathing difficulties [1].
  • Other medications, such as corticosteroids and immunosuppressants, may be prescribed to reduce inflammation and muscle damage [2].
• Experimental therapies: Researchers are exploring new therapeutic approaches for AD-CNM, including gene therapy and RNA-based treatments. However, these options are still in the experimental stages and not yet available for clinical use.
• Management of complications: Regular monitoring and management of potential complications, such as respiratory insufficiency and muscle weakness, are crucial to prevent further deterioration.

References:

[1] Dechene ET, et al. Mutation spectrum in the large GTPase dynamin 2, and genotyping-phenotype correlation in autosomal dominant centronuclear myopathy. Hum Mutat. 2018;39(10):1345-1354.

[2] Trochet D, Prudhon B, Beuvin M, et al. Allele-specific silencing therapy for dynamin 2-related dominant centronuclear myopathy. Embo Mol Med. 2018;10(2):e8441.

Note: The information provided is based on the search results and may not be comprehensive or up-to-date.

Autosomal dominant centronuclear myopathy (AD-CNM) is a rare genetic disorder that affects the muscles, and its differential diagnosis involves identifying other conditions that may present with similar symptoms.

Similar Conditions:

• Congenital Myotonic Dystrophy: This condition also presents with severe neonatal hypotonia and muscle weakness. However, it is characterized by myotonia (difficulty relaxing muscles after contraction) and cataracts [1].
• Facioscapulohumeral Muscular Dystrophy: This condition affects the muscles of the face, scapula, and humerus, and may present with similar symptoms to AD-CNM. However, it is typically inherited in an autosomal dominant pattern but has a distinct clinical presentation [2].
• Other Congenital Myopathies: These are a group of rare genetic disorders that affect the muscles and can present with similar symptoms to AD-CNM.

Key Diagnostic Features:

• **Centrally