congenital myasthenic syndrome 16

Congenital Myasthenic Syndrome (CMS) Description

Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, which worsens with physical exertion [1]. These disorders affect how nerve and muscle cells communicate, leading to muscle weakness and fatigue [5].

Characteristics:

• Muscle weakness that worsens with physical exertion
• Fatigue resulting from problems at the neuromuscular junction
• Affected individuals may experience difficulty with activities such as walking, running, or lifting objects

Causes:

• Genetic mutations in genes responsible for neuromuscular transmission
• Abnormal signal transmission at the motor endplate due to defects in single or multiple proteins [6]

References:

[1] Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, ...

[5] Like myasthenia gravis (MG), CMS is characterized by weakness and fatigue resulting from problems at the neuromuscular junction— the place where nerve and ...

[6] by AG Engel · 2015 · Cited by 549 — The congenital myasthenic syndromes are diverse disorders linked by abnormal signal transmission at the motor endplate that stem from defects in single or ...

Signs and Symptoms of Congenital Myasthenic Syndrome

Congenital myasthenic syndrome (CMS) is a group of inherited conditions that affect muscle strength and control. The signs and symptoms of CMS can vary in severity, but generally include:

• Muscle weakness: Muscle fatigue and weakness triggered by physical activity [1].
• Limited or lack of muscle movement: In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling, and walking) [5].
• Ptosis (droopy eyelids): Eyelid ptosis is a common symptom in CMS patients, often becoming fixed [8].
• Exercise intolerance: Mild to severe exercise intolerance can be a symptom of CMS, depending on the type [3].
• Floppiness and weak suck and cry: In infancy, signs and symptoms include floppiness, a weak suck and cry, choking spells, stiff joints, feeding and breathing difficulties, and hanging eye lids [9].

It's essential to note that the severity of CMS can range from minor symptoms to severe, disabling ones. The earlier the onset of symptoms, the more severe they tend to be.

References: [1] - Muscle fatigue and weakness triggered by physical activity. [3] - Severity can range from minor symptoms such as mild exercise intolerance to severe, disabling ones. [5] - In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). [8] - Nearly all patients have eyelid ptosis, oculoparesis that often becomes fixed, and variable but frequently moderate to severe limb muscle weakness.

Diagnostic Tests for Congenital Myasthenic Syndrome

Diagnosing congenital myasthenic syndrome (CMS) involves a combination of clinical evaluation, physical examination, and various diagnostic tests. Here are some of the key tests used to diagnose CMS:

• Physical Examination: A thorough physical examination is essential in diagnosing CMS. This includes a neurological exam to assess muscle strength, tone, and reflexes.
• Electromyography (EMG): EMG measures the electrical activity of muscles. It can help identify abnormal muscle activity patterns that are characteristic of CMS.
• Nerve Conduction Studies: These tests measure the speed and strength of nerve impulses. They can help identify abnormalities in nerve function that may be associated with CMS.
• Genetic Testing: Genetic testing can help identify specific genetic mutations that cause CMS. This is particularly useful for families with a history of CMS.
• Muscle Biopsy: A muscle biopsy involves taking a small sample of muscle tissue for examination under a microscope. It can help confirm the diagnosis of CMS and rule out other conditions.

Additional Tests

Other tests may be used to support the diagnosis of CMS, including:

• Imaging Studies: Imaging studies such as MRI or CT scans may be used to rule out other conditions that may cause similar symptoms.
• Blood Tests: Blood tests may be used to rule out other conditions that may cause similar symptoms.

References

• [3] A healthcare provider will diagnose congenital myasthenic syndrome after a physical and neurological exam. They’ll review your symptoms and take a complete medical history. If they suspect CMS, they may ask you to perform a physical activity under their supervision to observe how your body reacts, like walking up stairs, for example ...
• [5] Mayo Clinic doctors have extensive experience in diagnosing and treating congenital myasthenic syndromes. Cutting-edge medicine. Mayo Clinic doctors offer a wide range of tests to diagnose congenital myasthenic syndromes, including electromyography (EMG), nerve conduction studies and genetic testing to identify genes that cause the conditions.
• [10] Your doctor will do a physical examination ― including a neurological exam ― and review symptoms and medical history to check for signs of a congenital myasthenic syndrome. Your doctor may also order tests to exclude other conditions with similar symptoms. The following tests can help diagnose a congenital myasthenic syndrome and determine ...
• [11] An individual with a congenital myasthenic syndrome (CMS) typically presents with a history of fatigable weakness involving ocular, bulbar, and limb muscles with onset at or shortly after birth or in early childhood, usually in the first two years. ... Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used ...
• [14] one syndrome can be detrimental in another. Introduction The congenital myasthenic syndromes (CMS) are a group of inherited disorders in which neuromuscular trans-mission is impaired at the motor endplate (a special synaptic contact between motor axons and each skeletal muscle fi bre) by one or more specifi c mechanisms (panel 1, appendix).

Treatment Options for Congenital Myasthenic Syndrome

Congenital myasthenic syndromes (CMS) are a group of rare genetic disorders that affect the nerve-muscle connection, leading to muscle weakness and fatigue. While there is no cure for CMS, various drug treatments can help manage symptoms and improve quality of life.

Medications Used in Treatment

• Cholinesterase inhibitors: These medications, such as pyridostigmine (Mestinon), work by increasing the levels of acetylcholine (ACh) in the body, which is essential for proper muscle function. [1][2]
• β-Adrenergic agonists: Ephedrine has been shown to improve muscle strength in patients with CMS. [3]
• Open-channel blockers: These medications can also be used to treat CMS, although their optimal use depends on an accurate diagnosis of the underlying genetic mutation. [4]

Specific Treatment for Myasthenic Crises

In severe cases of CMS, myasthenic crises may occur, which require immediate treatment with plasmapheresis, immunoadsorption, or intravenous immunoglobulin (IVIG). [5]

Gene-Specific Treatment

The effectiveness of medication in treating CMS depends on the specific gene mutation responsible for the condition. For example, pyridostigmine is often used to treat CMS caused by mutations in the DOK7 gene. [6][7]

Avoiding Certain Medications

Individuals with CMS should avoid certain medications, such as antibiotics, cardiovascular drugs, and psychiatric medications, which can exacerbate muscle weakness symptoms. [8]

It's essential for patients with CMS to work closely with their healthcare providers to develop a personalized treatment plan that takes into account the specific genetic mutation and individual needs.

References:

[1] Farmakidis et al. (2018) - Cholinergic agents, β-adrenergic agonists, and open-channel blockers remain the principal treatment modalities... [4]

[2] Lashley et al. (2010) - This study provides Class IV evidence that ephedrine given at doses between 15 and 90 mg/day improves muscle strength in patients with CMS. [3]

[3] Kediha et al. (2024) - From a therapeutic point of view, the treatment of CMS is based on the use of medications such as pyridostigmine... [2]

[4] Engel et al. (1995) - Congenital myasthenic syndrome associated with paucity of synaptic vesicles and reduced acetylcholine release... [13]

[5] Knight et al. (2019) - The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations... [12]

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

Differential Diagnosis of Congenital Myasthenic Syndrome (CMS)

Congenital myasthenic syndrome (CMS) is a group of inherited conditions that are present from birth or early childhood. The differential diagnosis of CMS involves ruling out other conditions that may present with similar symptoms.

• Spinal Muscular Atrophy: This condition affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness and wasting. [7]
• Motor Neuron Disease: Conditions such as amyotrophic lateral sclerosis (ALS) can also cause progressive muscle weakness and atrophy.
• Peripheral Neuropathy: Certain types of peripheral neuropathy, such as Charcot-Marie-Tooth disease, can cause muscle weakness and wasting in the limbs. [8]
• Progressive Bulbar Palsy: This condition affects the nerve cells responsible for controlling voluntary muscle movement, leading to progressive muscle weakness and atrophy.
• Acute GQ1b Immune-Mediated Neuropathy: This is a rare condition that can cause rapid onset of muscle weakness and paralysis. [9]

It's essential to note that CMS has distinct clinical features, such as fatigable weakness affecting especially the ocular and other cranial muscles, which can help differentiate it from other conditions. [1][2] A comprehensive diagnostic evaluation, including genetic testing, electromyography (EMG), and muscle biopsy, may be necessary to confirm a diagnosis of CMS.

References: [1] by AG Engel · 2015 [7] by J Finsterer · 2007 [8] by MI Muñoz-García · 2023 [9] by SJ Bird [2] by J Finsterer · 2019