congenital myasthenic syndrome 7

Congenital Myasthenic Syndrome 7 (CMS7)

Congenital Myasthenic Syndrome 7, also known as CMS7, is a rare genetic disorder that affects neuromuscular transmission. It is characterized by presynaptic defects leading to symptoms such as muscle weakness, fatigue, and respiratory insufficiency.

Key Features:

• Presynaptic defects: The condition involves abnormalities in the nerve terminals or the motor endplates, which disrupt normal signal transmission.
• Muscle weakness: Affected individuals experience progressive muscle weakness, particularly in the distal muscles (those farthest from the center of the body).
• Respiratory insufficiency: In severe cases, CMS7 can lead to respiratory failure due to weakened diaphragm and intercostal muscles.
• Variable severity: The condition's severity ranges from mild to life-threatening, with some individuals experiencing disabling muscle weakness.

Inheritance Pattern: CMS7 is inherited in an autosomal dominant manner, meaning a single copy of the mutated gene is sufficient to cause the condition. This means that each child of an affected parent has a 50% chance of inheriting the mutated gene.

References:

• [9] Congenital myasthenic syndrome 7 is a genetic disorder inherited in an autosomal dominant manner. It is characterized by presynaptic defects leading to symptoms ...
• [11] Definition. Presynaptic congenital myasthenic syndrome-7A with distal motor neuropathy (CMS7A) is an autosomal dominant neuromuscular disorder characterized by onset of foot deformities, delayed motor development, and slowly progressive distal muscle weakness resulting in gait difficulties in early childhood.
• [12] Presynaptic congenital myasthenic syndrome-7A with distal motor neuropathy (CMS7A) is an autosomal dominant neuromuscular disorder characterized by onset of foot deformities, delayed motor development, and slowly progressive distal muscle weakness resulting in gait difficulties in early childhood.

Muscle Weakness and Fatigue

Congenital myasthenic syndrome, as mentioned in search result [7], is an inherited disorder that usually develops at or near birth or in early childhood. One of the primary signs and symptoms of this condition is muscle weakness and fatigue.

• Muscle Weakness: This can manifest as floppiness, a weak suck and cry, choking spells, stiff joints, feeding and breathing difficulties, and hanging eye lids.
• Fatigue: Muscle weakness triggered by physical activity is another common symptom of congenital myasthenic syndrome. As the muscles work harder to compensate for the weakness, they become increasingly fatigued.

These symptoms can vary in severity depending on the type of congenital myasthenic syndrome and may not always be immediately apparent at birth. In some cases, the condition may only be identified later in childhood or even early adulthood if the symptoms are mild.

References:

• Search result [7]: Congenital myasthenia is an inherited disorder that usually develops at or near birth or in early childhood and involves muscle weakness and fatigue.
• Search result [9]: In infancy, signs and symptoms include floppiness, a weak suck and cry, choking spells, stiff joints, feeding and breathing difficulties and hanging eye lids ( ... )
• Search result [11]: Symptoms range from mild to severe muscle weakness and may get worse over time or only occur periodically.

Diagnostic Tests for Congenital Myasthenic Syndrome 7 (CMS7)

Congenital Myasthenic Syndrome 7 (CMS7) is a rare neuromuscular disorder characterized by progressive distal muscle weakness, delayed motor development, and foot deformities. Diagnosing CMS7 can be challenging, but various diagnostic tests can help confirm the condition.

Genetic Testing

• Next-generation sequencing: This test detects single nucleotide and copy number variants in 28 genes associated with congenital myasthenic syndromes, including CMS7 [4].
• Targeted gene panel testing: Specific genetic testing panels, such as the Blueprint Genetics Congenital Myasthenic Syndromes Panel (test code NE1701), can be used to detect mutations in the CMS7A gene [3].

Physiological Tests

• Repetitive nerve stimulation (RNS): This test is usually decremental in CMS7, and single fiber electromyography (SFEMG) yields increased jitter and blocking [9].
• Muscle biopsy: A muscle biopsy can be performed to exclude other conditions with similar symptoms and to obtain tissue for molecular diagnosis.

Other Diagnostic Tests

• Physical examination: A thorough physical examination, including a neurological exam, is essential to check for signs of CMS7.
• Medical history review: Reviewing the patient's medical history can help identify any family history of myasthenic symptoms or other relevant conditions [12].

It's essential to note that genetic testing and physiological tests may be needed to define some types of CMS7. A definitive genetic diagnosis can be obtained through targeted gene panel testing or next-generation sequencing.

References:

[3] Blueprint Genetics Congenital Myasthenic Syndromes Panel (test code NE1701) [4] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with congenital myasthenic syndromes. [9] Repetitive nerve stimulation (RNS) is usually decremental in CMS, and single fiber electromyography (SFEMG) yields increased jitter and blocking. [12] A family history of myasthenic symptoms supports the CMS diagnosis but isn't necessary for CMS to occur.

Treatment Options for Congenital Myasthenic Syndrome (CMS)

Congenital Myasthenic Syndrome (CMS) is a rare genetic disorder that affects 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.

Current Treatment Modalities

According to recent studies [5], cholinergic agents, β-adrenergic agonists, and open-channel blockers remain the principal treatment modalities for CMS. These include:

• Cholinergic Agents: Such as acetylcholine esterase inhibitors (e.g., pyridostigmine) that increase the concentration of acetylcholine in the synaptic cleft [6].
• β-Adrenergic Agonists: Like salbutamol and ephedrine, which can be used as first-line pharmacological treatments for CMS [3].
• Open-Channel Blockers: Such as quinidine and fluoxetine, which can help normalize the opening of acetylcholine receptors (AChRs) [6].

Other Treatment Options

In addition to these primary treatment modalities, other drugs may be used to manage specific symptoms or complications associated with CMS. For example:

• 3,4-DAP: A drug that increases the quanta of acetylcholine released by the nerve, which can help improve muscle strength [7].
• Fluoxetine and Quinidine: These long-lived open-channel blockers can be useful when the synaptic response is increased by abnormally prolonged opening of AChRs [6].

Important Considerations

It's essential to note that some drugs should be avoided in people with CMS, as they can exacerbate symptoms or interact with other medications. For instance:

• Antibiotics, cardiovascular drugs, and drugs for psychiatric conditions should be used cautiously or avoided altogether [8].

Overall, the treatment of CMS requires a comprehensive approach that takes into account the individual's specific needs and medical history. A multidisciplinary team of healthcare professionals can work together to develop an effective treatment plan.

References:

[3] by S Shao · 2023 · Cited by 4 — Our meta-analysis revealed evidence that β-adrenergic agonists, including salbutamol and ephedrine, can be used as first-line pharmacological treatments for CMS ...

[5] by C Farmakidis · 2018 · Cited by 44 — Cholinergic agents, β-adrenergic agonists, and open-channel blockers remain the principal treatment modalities, and their optimal use depends on ...

[6] by AG Engel · 2007 · Cited by 125 — Long-lived open-channel blockers of the AChR, quinidine, and fluoxetine, are useful when the synaptic response is increased by abnormally prolonged opening ...

[7] by MI Kediha · 2024 — 3,4 DAP increases the quanta of ACh released by the nerve, fluoxetine, and quinidine induce a shortening or even a normalization of the opening ...

[8] Some drugs such as antibiotics, cardiovascular drugs and drugs for psychiatric conditions should be avoided by people with Congenital myasthenic syndrome (CMS) ...

Differential Diagnosis of Congenital Myasthenic Syndrome

The differential diagnosis of congenital myasthenic syndromes (CMS) is a crucial aspect of diagnosing this condition. According to various medical sources, the differential diagnosis of CMS includes:

• Spinal muscular atrophy: This is a genetic disorder that affects the nerve cells responsible for controlling voluntary muscle movement.
• Motor neuron disease: This is a group of rare neurological disorders that affect the motor neurons, which are responsible for transmitting signals from the brain to the muscles.
• Peripheral neuropathy: This refers to damage or dysfunction of the peripheral nerves, which can cause weakness, numbness, and pain in the affected areas.

Additionally, CMS should also be considered in the differential diagnosis of seronegative myasthenia gravis and other neuromuscular disorders.

Key Points:

• CMS is a genetic disorder that affects neuromuscular transmission.
• The differential diagnosis of CMS includes spinal muscular atrophy, motor neuron disease, peripheral neuropathy, and other neuromuscular disorders.
• Accurate diagnosis of CMS requires careful consideration of these differential diagnoses.

References:

[7] The congenital myasthenic syndromes are diverse disorders linked by abnormal signal transmission at the motor endplate that stem from defects in single or multiple proteins. Multiple endplate proteins are affected by mutations of single enzymes required for protein glycosylation, and deletion mutations affecting the AChR subunits.