autosomal recessive centronuclear myopathy

Autosomal recessive centronuclear myopathy (AR-CNM) is a rare, inherited condition that affects the muscles. It is characterized by muscle weakness and wasting, particularly in the skeletal muscles.

Key Features:

• Inheritance: AR-CNM is inherited in an autosomal recessive manner, meaning that both copies of the gene in each cell have mutations.
• Age of Onset: Affected individuals typically begin showing signs and symptoms during infancy or early childhood.
• Muscle Weakness: Muscle weakness and wasting are common features of AR-CNM, particularly in the skeletal muscles.
• Facial Weakness: Facial weakness is a characteristic feature of AR-CNM.
• Ocular Abnormalities: Ocular abnormalities such as ptosis (drooping eyelids) and external ophthalmoplegia (weakness of the eye muscles) are also common.

Genetic Forms:

AR-CNM is caused by mutations in several genes, including BIN1, TTN, and RYR1. These genes play a crucial role in muscle function and development.

Severity and Progression:

The severity and progression of AR-CNM can vary among affected individuals, even within the same family. Some people may experience more severe symptoms than others.

References:

• [3] Centronuclear myopathies caused by TTN gene mutations and most cases caused by BIN1 gene mutations are inherited in an autosomal recessive pattern.
• [4] Autosomal-dominant or recessive mutations in BIN1 (2q14.3), encoding myc box-dependent-interacting protein 1, have been associated with AR-CNM.
• [5] Children with autosomal recessive centronuclear myopathies typically have some neuromuscular impairment as they grow and develop.
• [7] The autosomal recessive (AR) form of centronuclear myopathy causes progressive muscle weakness, is less severe than myotubular myopathy and affects both males and females.

Autosomal Recessive Centronuclear Myopathy (AR-CNM) is a rare genetic disorder that affects the muscles. The signs and symptoms of AR-CNM can vary in severity, but they often include:

• Facial weakness: People with AR-CNM may experience droopy eyelids (ptosis) and weakness in other facial muscles, including those that control eye movement [2].
• Muscle weakness: AR-CNM is characterized by muscle weakness, particularly in the masticatory muscles (those used for chewing), and ocular abnormalities such as ptosis and external ophthalmoplegia [3].
• Hypotonia: Muscle tone is often diminished, leading to a lack of muscle strength and coordination.
• Feeding difficulties: In severe cases, people with AR-CNM may experience feeding difficulties due to weakness in the muscles used for swallowing and chewing [1].
• Respiratory distress: Severe forms of AR-CNM can lead to respiratory distress, which is a life-threatening condition that requires immediate medical attention.
• Extraocular muscle involvement: The extraocular muscles (those controlling eye movement) are often affected, leading to ptosis and other eye-related symptoms [6].

It's essential to note that the severity and progression of AR-CNM can vary significantly from person to person. Early diagnosis and treatment by a qualified healthcare professional are crucial for managing the condition and improving quality of life.

References:

[1] Context result 4: Myotubular myopathy causes muscle weakness and hypotonia (lack of muscle tone) noticeable at birth. [2] Context result 2: People with centronuclear myopathy may have droopy eyelids (ptosis ) and weakness in other facial muscles, including the muscles that control ... [3] Context result 3: AR-CNM is characterized by facial weakness including severe involvement of the masticatory muscles, and ocular abnormalities such as ptosis and external ... [6] Context result 6: In the severe forms the common symptoms include hypotonia, feeding difficulties and respiratory distress. Extraocular muscle involvement is also common in all ...

Autosomal recessive centronuclear myopathy (AR-CNM) can be diagnosed through a combination of clinical evaluation, muscle biopsy, and genetic testing.

• Muscle Biopsy: A muscle biopsy is often required to support the potential diagnosis of AR-CNM and to differentiate it from other types of myopathy. The biopsy typically shows numerous centrally placed nuclei on muscle fibers [12].
• Genetic Testing: Molecular genetic testing is available as a diagnostic service at specialized laboratories, which can confirm the diagnosis by identifying mutations in the BIN1 gene associated with AR-CNM [2]. Genetic testing may also involve targeted variant analysis, deletion/duplication analysis, mutation scanning of select exons, or sequence analysis of the BIN1 gene [7].
• Muscle MRI: Muscle MRI may be helpful to distinguish AR-CNM from other forms of centronuclear myopathy and can provide additional information on muscle involvement [9].

It's worth noting that a diagnosis of AR-CNM is typically made by a combination of clinical evaluation, muscle biopsy, and genetic testing. A doctor may also use differential diagnoses to rule out other conditions such as congenital myopathies, myotonic dystrophy, or facial involvement in the case of prominent facial weakness [1].

References: [1] Context result 4 [2] Context result 2 [7] Context result 3 [9] Context result 9 [12] Context result 12

Based on the available information, it appears that there is no specific drug treatment for autosomal recessive centronuclear myopathy (AR-CNM). However, some individuals with AR-CNM have been reported to benefit from the use of salbutamol, a medication commonly used in the treatment of bronchial asthma.

• Salbutamol has been used with some benefit in individuals with RYR1-related myopathies such as some forms of CNM [1].
• However, it is essential to note that AR-CNM is a rare and inherited condition, and more research is needed to fully understand its treatment options.
• Currently, management of symptoms is the primary approach for treating AR-CNM, with no curative treatment available [5][8].

It's also worth noting that there are ongoing therapeutic proof-of-concept studies for congenital myopathies, including centronuclear myopathy, but these have not yet led to approved therapies [6].

Autosomal recessive centronuclear myopathy (AR-CNM) is a rare, inherited neuromuscular disorder that affects the muscles. When diagnosing AR-CNM, it's essential to consider other conditions with similar symptoms and characteristics.

Differential Diagnoses:

• Congenital Myopathies: These are a group of muscle disorders present at birth, characterized by muscle weakness and wasting. Other forms of congenital myopathies can be considered in the differential diagnosis of AR-CNM.
• Myotonic Dystrophy: This is a genetic disorder that affects muscle tone, leading to stiffness and spasms. Myotonic dystrophy can present with similar symptoms to AR-CNM, such as muscle weakness and wasting.
• Facioscapulohumeral Dystrophy: This is another type of muscular dystrophy that primarily affects the muscles of the face, scapula, and humerus. It can be considered in the differential diagnosis if facial involvement is prominent.

Other Conditions:

• X-linked Myotubular Myopathy: This is a rare genetic disorder that affects muscle development and function. While it has distinct clinical features, it's essential to consider X-linked myotubular myopathy in the differential diagnosis of AR-CNM.
• Mitochondrial Myopathies: These are a group of disorders affecting the mitochondria, leading to muscle weakness and wasting. Mitochondrial myopathies can be considered in the differential diagnosis if there is evidence of mitochondrial dysfunction.

Key Points:

• The main differential diagnoses for autosomal recessive centronuclear myopathy include congenital myopathies, myotonic dystrophy, facioscapulohumeral dystrophy, X-linked myotubular myopathy, and mitochondrial myopathies.
• A comprehensive diagnostic evaluation is necessary to distinguish AR-CNM from these other conditions.

References:

• Spiro et al. (1966) - First reported case of myotubular myopathy
• MTM1, RYR1, DNM2, and BIN1 mutations associated with CNM and related disorders
• Clinical differences exist between the three forms of myotubular myopathy