Cma

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 due to defects at the neuromuscular junction. These conditions are present from birth or early childhood and result from 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 abnormalities in 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.

Genetics

CMS are caused by mutations in various genes, including:

• CHRNA1, CHRNB1, CHRND, and CHRNE: These genes encode subunits of the acetylcholine receptor.
• RAPSN: This gene encodes rapsyn, a protein essential for clustering acetylcholine receptors at the neuromuscular junction.
• COLQ: This gene encodes a protein involved in anchoring acetylcholinesterase in the synaptic cleft.

Clinical Features

Patients with CMS typically present with:

• 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. Electromyography (EMG) and nerve conduction studies can help assess neuromuscular transmission. Genetic testing can identify specific mutations responsible for the condition.

Management

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

• Acetylcholinesterase inhibitors: Such as pyridostigmine, which increase the availability of acetylcholine at the neuromuscular junction.
• 3,4-diaminopyridine: A potassium channel blocker that enhances acetylcholine release.
• Supportive care: Including physical therapy and respiratory support as needed.

Prognosis

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

See Also

• Myasthenia Gravis
• Neuromuscular Disorders

External Links

• Muscular Dystrophy Association - Congenital Myasthenic Syndromes