Cmas

Congenital Myasthenic Syndromes
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Muscle weakness, fatigue
Complications	N/A
Onset	Birth or early childhood
Duration	Lifelong
Types	N/A
Causes	Genetic mutations
Risks	Family history
Diagnosis	Clinical evaluation, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Acetylcholinesterase inhibitors, 3,4-diaminopyridine, supportive care
Medication	N/A
Prognosis	Variable
Frequency	N/A
Deaths	N/A

Congenital Myasthenic Syndromes (CMS) are a group of genetic disorders characterized by muscle weakness and fatigue resulting from defects at the neuromuscular junction. These syndromes are present from birth or early childhood and are caused by mutations in genes that are critical for neuromuscular transmission.

Classification

CMS can be classified based on the location of the defect within the neuromuscular junction:

• Presynaptic CMS: These involve defects in the release of acetylcholine from the nerve terminal.
• Synaptic CMS: These involve defects in the synaptic cleft, often due to mutations affecting the enzyme acetylcholinesterase.
• Postsynaptic CMS: These involve defects in the acetylcholine receptor or associated proteins on the muscle membrane.

Pathophysiology

The neuromuscular junction is a specialized synapse between a motor neuron and a muscle fiber. In CMS, genetic mutations disrupt the normal function of this junction, leading to impaired transmission of nerve signals to muscles. This results in the characteristic muscle weakness and fatigue seen in affected individuals.

Presynaptic Defects

Presynaptic CMS is often due to mutations in genes such as CHAT (choline acetyltransferase), which is responsible for the synthesis of acetylcholine. Defects in this enzyme lead to reduced availability of acetylcholine for release into the synaptic cleft.

Synaptic Defects

Synaptic CMS is typically caused by mutations affecting acetylcholinesterase, the enzyme responsible for breaking down acetylcholine in the synaptic cleft. This can lead to prolonged action of acetylcholine and subsequent desensitization of the postsynaptic receptors.

Postsynaptic Defects

Postsynaptic CMS is the most common form and involves mutations in the acetylcholine receptor subunits or associated proteins such as rapsyn. These mutations can lead to reduced receptor density or impaired receptor function, resulting in decreased muscle response to nerve signals.

Clinical Features

The clinical presentation of CMS is highly variable, but common features include:

• Muscle weakness that worsens with exertion
• Ptosis (drooping of the eyelids)
• Ophthalmoplegia (weakness of the eye muscles)
• Bulbar symptoms such as difficulty swallowing
• Respiratory difficulties in severe cases

Diagnosis

Diagnosis of CMS involves a combination of clinical evaluation, electrophysiological studies, and genetic testing. Key diagnostic steps include:

• Electromyography (EMG) to assess muscle response
• Repetitive nerve stimulation tests
• Genetic testing to identify specific mutations

Treatment

Treatment of CMS is tailored to the specific genetic defect and may include:

• Acetylcholinesterase inhibitors such as pyridostigmine to enhance neuromuscular transmission
• 3,4-diaminopyridine to increase acetylcholine release
• Supportive therapies such as physical therapy and respiratory support

Prognosis

The prognosis for individuals with CMS varies depending on the specific genetic mutation and the severity of symptoms. Some individuals may experience significant improvement with treatment, while others may have persistent symptoms.

See Also

• Myasthenia Gravis
• Neuromuscular Junction
• Genetic Disorders