This is a rare hereditary condition developing from a defect at the neuromuscular junction that is responsible for the stimulation by the nerves for muscle activity. As a result, muscle weakness occurs that typically becomes worse with exercise. The muscle weakness can occur in early childhood, adolescence or adulthood. The facial muscles commonly affected are the ones that control the eyelids, the movement of the eyes and the muscles used for swallowing and chewing. This condition can affect any of the muscles used for movement. The severity of this syndrome varies among the affected individuals with some experiencing minor weakness to others presenting severe weakness causing disability. There are around ten different types of congenital myasthenic syndromes which are divided into presynaptic, synaptic and postsynaptic dysfunction based on the parts of the junction between the muscle and the nervous system where the dysfunction occurs.
Causes
There are several genes identified as the cause of this condition. The genetic mutation in CHRNE gene is responsible for most of the cases. Others may develop this condition as the result of mutations in the RAPSN, CHAT, COLO and DOK7 genes. All these genes are responsible for the production of proteins necessary for the function of the neuromuscular junction, the space where the nerve cells and the muscles connect. The genetic mutation disrupts the normal signaling process between the ends of the nerve cells and the muscle cells. As the result, the movement of the skeletal muscles become impaired along with muscle weakness and delayed development of motor skills. Among some of the cases, the genetic mutation is not identified and hence the cause of these cases remains unknown. The condition is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. Rarely, it can be inherited in an autosomal dominant pattern meaning a single copy of the defective gene in each cell can cause the condition.
Symptoms
This condition is characterized by the weakness of the muscle that can be induced or made worse with exercise. The muscle weakness can cause double vision, droopy eyelids, facial weakness, slurred speech, and swallowing difficulties. In other cases, the weakness of the limb and torso muscles can also occur. In some cases, it can cause developmental delays, seizures, metabolic abnormalities and intellectual disability. The respiratory problems associated with this condition results from the impaired movement of the chest wall muscles.
Diagnosis
The diagnosis is based on the history of fatigable weakness of the ocular muscles, bulbar muscles and limb muscles since infancy or early childhood. A decremental electromyographic (EMG) response and negative tests for antibodies against the acetylcholine receptor (AChR) and the muscle receptor tyrosine kinase can help determine the condition. In some cases, the onset of the disease may be delayed, the family history of the condition is negative and EMG abnormalities may not be present. An EMG test records the electrical activity of the voluntary muscles at rest and during contraction. A genetic mutation can also help determine the specific gene responsible for the cause of the condition.
Treatment
The treatment for this condition is based on medications such as cholinesterase inhibitors which can increase the effectiveness of the acetylcholine neurotransmitter. Other forms of treatment include the long-lived channel blockers of acetylcholine receptor ion channel fluoxetine and quinidine. A genetic counseling may be beneficial for some of the affected individuals and their family members.
References
https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome
https://rarediseases.org/rare-diseases/congenital-myasthenic-syndromes/
http://www.congenitalmyasthenicsyndrome.info/
