Introduction
Congenital myasthenia gravis is an inherited disorder affecting the nerve-muscle relationship. It differs from myasthenia gravis, an autoimmune disorder where antibodies are formed and disrupt neurotransmission. However, in congenital myasthenia gravis, genetic alteration is the cause.
What Is Congenital Myasthenia Gravis?
Congenital myasthenia gravis is a hereditary neuromuscular disorder affecting the neuromuscular junction (NMJ). A general weakness of muscles characterizes it. The nervous system and muscles work together to control the movements in our body. In this condition, there is a lack of coordination in the absence of communication between nerve cells and muscles.
What Is the Cause of Congenital Myasthenia Gravis?
The body's various functions, like walking, talking, and breathing, occur through communication between muscles and nerves. A nerve impulse travels from one end of a nerve cell to another. When the impulse reaches the end of a neuron, chemicals called neurotransmitters are released, which carry the impulse from one neuron to another. The muscle receives the impulse, and thus the function assigned to that muscle takes place. When there is some disturbance in this process, it results in myasthenia gravis. A mutation or alteration in the genes responsible for producing proteins for the proper functioning of the neuromuscular junction causes congenital myasthenia gravis.
Some of the genes that are mutated are:
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CHRNE - Cholinergic receptor nicotine epsilon subunit.
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RAPSN - Receptor-associated protein of the synapse.
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CHAT - Choline O-acetyltransferase.
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COLQ - Collagen-like tail subunit of asymmetric acetylcholinesterase.
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DOK7 - Docking protein 7.
What Are the Signs and Symptoms of Congenital Myasthenia Gravis?
The symptoms presented in infants are:
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Decreased baby movements inside the womb.
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Fatigability.
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Difficulty sucking on a pacifier.
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Decreased activity.
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Breathing difficulty.
The symptoms present in children and adults are:
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Decreased tone in muscles.
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Reduced mobility.
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Weakness of eye, mouth, and throat muscles.
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Delay in the ability to sit, crawl, or walk.
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The curvature of the spine.
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Droopy eyelids.
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Difficulty in chewing and swallowing.
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Frequent lung infections.
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Difficulty playing sports or doing day-to-day activities.
What Is the Inheritance Pattern in Congenital Myasthenia Gravis?
Congenital myasthenia gravis is inherited in an autosomal recessive manner, which means a person shows symptoms only if they receive one copy of the defective gene from each of their parents. There is a 25 percent chance in every pregnancy that the child will inherit this disease.
Another type of congenital myasthenia gravis is inherited in an autosomal dominant manner, which means only one copy of the defective gene from any one of the parents can inherit the disease. However, there is a 50 percent chance of the child inheriting this condition with every pregnancy.
What Are the Risk Factors for Congenital Myasthenia Gravis?
Congenital myasthenia gravis is usually caused by genetic mutations affecting neuromuscular junction proteins. Risk factors include:
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The primary risk factor for congenital myasthenia gravis is a family history of the condition.
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If both parents carry a copy of a mutated gene associated with congenital myasthenia gravis, there is an increased risk of having an affected child.
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The risk of congenital myasthenia gravis may be higher in populations or families where there is a high degree of consanguinity.
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Certain genetic mutations associated with CMG may be more prevalent in specific ethnic or racial groups.
What Are the Types of Congenital Myasthenia Gravis?
1)Presynaptic Congenital Myasthenia Gravis (Nerve End):
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Nerve cells struggle to release enough acetylcholine for proper signal transmission.
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This results in weak muscle signaling and muscle weakness.
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Gene mutations affecting acetylcholine production are the cause.
2)Postsynaptic Congenital Myasthenia Gravis (Muscle End):
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In this type, there are not enough acetylcholine receptors, leading to insufficient signal transmission and weak muscle movement.
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Causes:
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Lack of extracellular matrix proteins for receptor clustering.
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Defect in glycosylation, changing the shape of proteins.
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Fast-channel: Receptors do not stay open long enough.
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Slow-channel: Receptors stay open too long.
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Results in disrupted impulse transmission, no muscle contraction.
3)Synaptic Congenital Myasthenia Gravis:
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Defective or absent acetylcholinesterase enzyme.
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This results in the accumulation of acetylcholine in the synaptic cleft, which leads to disturbed neurotransmission, preventing muscle contraction.
How Is Congenital Myasthenia Gravis Diagnosed?
A neurologist makes the diagnosis.
1. General Assessment:
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A history of symptoms like difficulty in feeding, and walking, decreased mobility, and delays in achieving milestones will help diagnose this condition.
2. Genetic Study:
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If someone in the same family has the same disease symptoms, gene testing and genome sequencing are done to find the genetic mutations.
3. Serum Test:
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The serum creatine kinase level is slightly elevated.
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Anti-acetylcholine receptor and anti-muscle tyrosine kinase antibodies are negative.
4. Electromyography:
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The electrical activity of the skeletal muscle is recorded through electromyography (EMG) when the muscle is at rest and during contraction.
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A motor nerve that supplies the skeletal muscle is stimulated. The electrical activity called an action potential, is recorded using the values picked up by electrodes placed in the muscle to be stimulated.
How Is Congenital Myasthenia Gravis Treated?
There is no specific treatment to cure this disorder since the underlying genetic defect can not be corrected. Another reason for the need for a standardized protocol for treatment is its rarity. Very limited research is done on a handful of patients. However, the symptoms can be managed and alleviated by medication. The treatment depends on the subtype of congenital myasthenia. Medication and treatment for one subtype may not be beneficial to other subtypes. Since it is a genetic disorder and not an immune-related disorder, immunosuppressants are not used.
Medications That Are Used Include:
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Cholinergic Agonists- Pyridostigmine and Amifampridine (3,4-diaminopyridine) are used to treat the postsynaptic fast channel congenital myasthenic syndrome.
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Adrenergic Agonists- Salbutamol and Ephedrine are the adrenergic agonists that act by stimulating the adrenergic receptors.
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Acetylcholine Receptor Blockers- Fluoxetine and Quinidine are used to treat the postsynaptic slow channel type of congenital myasthenia gravis.
General Supportive Treatment: The patient should take adequate rest after physical exertion to prevent the symptoms from becoming severe, like respiratory insufficiency.
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Therapies like physical, speech, and occupation therapy help maintain function in congenital myasthenia gravis.
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Supportive devices like wheelchairs and walkers may be recommended.
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Breathing issues might require an apnea monitor, and noninvasive ventilation (CPAP) could aid breathing.
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In severe cases, a tube for enteral nutrition may be inserted through the skin into the stomach or small intestine.
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Surgery might be necessary for severe orthopedic deformities.
Conclusion:
The prognosis of this disease depends on various factors, like the type of gene mutated, the age of onset of symptoms, the severity of symptoms, and the muscles affected. Affected people have a normal life expectancy if their symptoms are mild. However, the symptoms can vary greatly, from mild weakness on exertion or exercise to respiratory failure. Some symptoms can improve with age, while others may worsen or remain the same.
