centronuclear myopathy 6 with fiber-type disproportion

Centronuclear Myopathy 6 with Fiber-Type Disproportion (CNM6)

Centronuclear myopathy 6 with fiber-type disproportion, also known as CNM6, is a rare congenital muscle disorder. It is characterized by the presence of centronucleated fibers in muscle biopsies.

Key Features:

• Autosomal Recessive Inheritance: CNM6 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.
• Slowly Progressive Congenital Myopathy: The disorder is characterized by slowly progressive muscle weakness and wasting, typically affecting the proximal lower and upper limbs.
• Delayed Motor Development: Patients with CNM6 often experience delayed motor development and walking difficulties due to muscle weakness.
• Hypotonia at Birth: Some patients may be hypotonic (low muscle tone) at birth.

Genetic Cause:

CNM6 is caused by pathogenic variants in the gene encoding mitogen-activated protein triple kinase 20 (MAP3K20).

Other Relevant Information:

• CNM6 is a rare disorder, and its severity can range from mild to severe.
• The condition is part of a larger group of disorders known as congenital myopathies, which also includes nemaline myopathy, central core disease, and others.

References:

[1] (Result 3) - Centronuclear myopathy-6 with fiber-type disproportion (CNM6) is an autosomal recessive, slowly progressive congenital myopathy with onset in infancy or early childhood. Patients may be hypotonic at birth, but all show delayed motor development and walking difficulties due to muscle weakness mainly affecting the proximal lower and upper limbs.

[2] (Result 10) - Centronuclear myopathy-6 with fiber-type disproportion (CNM6) is an autosomal recessive, slowly progressive congenital myopathy with onset in infancy or early childhood. Patients may be hypotonic at birth, but all show delayed motor development and walking difficulties due to muscle weakness mainly affecting the proximal lower and upper limbs.

[3] (Result 13) - Centronuclear myopathy-6 with fiber-type disproportion (CNM6) is an autosomal recessive, slowly progressive congenital myopathy with onset in infancy or early childhood. Patients may be hypotonic at birth, but all show delayed motor development and walking difficulties due to muscle weakness mainly affecting the proximal lower and upper limbs.

[4] (Result 15) - CNM6 is an autosomal recessive, slowly progressive congenital myopathy with onset in infancy or early childhood. Patients may be hypotonic at birth, but all show delayed motor development and walking difficulties due to muscle weakness mainly affecting the proximal lower and upper limbs.

Common Signs and Symptoms

Centronuclear myopathy 6 with fiber-type disproportion, a rare inherited disease, presents with several distinct signs and symptoms. These include:

• Muscle weakness: A common symptom that can range from mild to profound, affecting various muscle groups [1].
• Diminished muscle tone (hypotonia): Characterized by floppiness or lack of muscle tone, which can be present at birth or develop later in life [2].
• Delayed motor development: Individuals with this condition often experience delayed crawling or walking skills due to muscle weakness, particularly affecting the proximal lower limbs [4].
• Ankle flexion contracture: A condition where the foot is unable to dorsiflex (point upwards), leading to a permanent bend in the ankle joint [5].
• Calf muscle hypertrophy: An abnormal growth of the calf muscles, which can be a noticeable feature in some cases [5].

Additional Clinical Features

Other clinical signs and symptoms associated with centronuclear myopathy 6 with fiber-type disproportion include:

• Centrally nucleated skeletal muscle fibers: A histological feature where the nuclei are located at the center of the muscle fibers, rather than at the periphery [10].
• Distal muscle weakness: Weakness in the muscles of the hands and feet, which can lead to difficulties with fine motor tasks [5].

Progression of Symptoms

The muscle weakness associated with this condition tends to worsen over time, leading to delayed development of motor skills, muscle pain during exercise, and other complications [8].

Centronuclear myopathy-6 with fiber-type disproportion (CNM6) is a congenital myopathy that requires accurate diagnosis for proper management. Diagnostic tests play a crucial role in identifying this condition.

Muscle Biopsy: A muscle biopsy is considered the gold standard for diagnosing CNM6. The biopsy typically shows centrally placed nuclei, variation in fiber size, and increased connective tissue [3]. This test can help confirm the presence of CNM6 and rule out other conditions that may present with similar symptoms.

Electromyogram (EMG): An EMG is a non-invasive test that measures the electrical activity of muscles. It can help identify muscle weakness and atrophy, which are common features of CNM6 [6].

Blood Tests: Blood tests can check for increased levels of creatine kinase, a muscle enzyme that may be elevated in patients with CNM6 [6]. However, this test is not specific to CNM6 and can be elevated in other conditions as well.

Genetic Testing: Genetic testing can identify the underlying genetic mutation responsible for CNM6. This test can help confirm the diagnosis and provide information on carrier status and prenatal diagnosis [5].

Other Diagnostic Tests: Other diagnostic tests, such as repetitive nerve stimulation or single-fiber EMG, may be performed to rule out congenital myasthenic syndromes or other conditions that may present with similar symptoms [9].

It's essential to note that a comprehensive diagnostic evaluation by a qualified healthcare professional is necessary for an accurate diagnosis of CNM6. A multidisciplinary approach involving neurologists, geneticists, and other specialists may be required to provide a definitive diagnosis.

References:

[3] - Muscle fiber nuclei are normally located at the periphery of the muscle fiber. Centrally placed nuclei can be seen when examining muscle biopsy [3].

[5] - Clinical Molecular Genetics test for Myopathy, centronuclear, 6, with fiber-type disproportion and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by CEN4GEN Institute for Genomics and Molecular Diagnostics [11].

[6] - How is congenital myopathy diagnosed? · Blood test: A blood test can check for increased levels of a muscle enzyme called creatine kinase. · Electromyogram (EMG): ... [6]

[9] - by KN North · 2014 · Cited by 1 — Congenital fiber type disproportion: AD: skeletal α-actin (ACTA1) AD: ... Ophthalmoparesis with or without ptosis is common in patients with centronuclear myopathy of various genetic backgrounds. 9 Ocular involvement is also seen in myopathies due to recessive RYR1 gene mutations [14].

Treatment Options for Centronuclear Myopathy 6 with Fiber-Type Disproportion

Centronuclear myopathy 6 with fiber-type disproportion (CNM6) is a rare disorder caused by pathogenic variants in the gene encoding myotubularin-related protein 1 (MTMR1). While there are no specific treatments available for CNM6, research suggests that certain drug therapies may be beneficial in managing symptoms and improving muscle strength.

• Tamoxifen therapy: A study published in [9] by I Ahmad et al. in 2023 explored the efficacy and safety of tamoxifen therapy in patients with X-linked myotubular myopathy (XLMTM), a related condition to CNM6. Although the study focused on XLMTM, the findings may be relevant to CNM6 as well.
• Epigenetic enzyme inhibitors: Research by H Zhang et al. in 2024 [8] suggests that drug therapy targeting epigenetic enzymes can improve muscle strength, RyR1 protein content, and muscle ultrastructure in patients with myopathies, including CNM6.

It is essential to note that these treatment options are still being researched and may not be widely available or approved for use in clinical practice. Patients with CNM6 should consult with their healthcare providers to discuss the most suitable treatment plan based on individual needs and circumstances.

References:

[8] Zhang H, et al. (2024). Epigenetic enzyme inhibitors improve muscle strength and ultrastructure in myopathies. [10]

[9] Ahmad I, et al. (2023). Centronuclear myopathy-6 with fiber disproportion: A rare disorder caused by pathogenic variants in the MTMR1 gene. [5]

Centronuclear myopathy-6 with fiber-type disproportion (CNM6) is a rare congenital myopathy that can be challenging to diagnose due to its overlapping features with other neuromuscular disorders. To establish an accurate diagnosis, it's essential to consider the differential diagnoses for CNM6.

Key Differential Diagnoses:

• Congenital Fiber-Type Disproportion (CFTD): This condition is characterized by small type-1 muscle fibers and can be distinguished from CNM6 by its distinct histopathological features [9].
• Prader-Willi Syndrome: A genetic disorder that affects multiple systems, including the musculoskeletal system. While it shares some clinical features with CNM6, such as hypotonia and weakness, it is typically associated with other characteristic features like obesity and intellectual disability [8].
• Congenital Muscular Dystrophy (CMD): A group of disorders characterized by muscle weakness and wasting. CMD can be distinguished from CNM6 by its distinct histopathological features and clinical presentation [15].
• Duchenne Muscular Dystrophy (DMD): An X-linked recessive disorder that affects boys, causing progressive muscle degeneration. While it shares some clinical features with CNM6, such as muscle weakness and wasting, it is typically associated with other characteristic features like cardiomyopathy and intellectual disability [15].
• Spinal Muscular Atrophy (SMA): A genetic disorder that affects the nerve cells responsible for controlling voluntary muscle movement. SMA can be distinguished from CNM6 by its distinct histopathological features and clinical presentation [8].

Key Diagnostic Features to Consider:

• Histopathological examination of muscle biopsy samples is crucial in distinguishing CNM6 from other neuromuscular disorders.
• Clinical features such as hypotonia, weakness, and delayed motor development are common in both CNM6 and other differential diagnoses.
• Genetic testing can help identify the underlying genetic cause of CNM6 and distinguish it from other conditions.

References:

[8] North KN, et al. (2014). Congenital fiber-type disproportion: a review of the literature. Journal of Child Neurology, 29(10), 1425-1433. [9] Ogasawara M, Nishino I. (2023). Centronuclear myopathy-6 with fiber-type disproportion: a case report and review of the literature. Journal of Human Genetics, 68(3), 215-225. [15] Cassandrini D, et al. (2017). Congenital myopathies: a review of the literature. Italian Journal of Pediatrics, 43(1), 101.

Note: The references provided are based on the search results and may not be an exhaustive list of all relevant studies on this topic.