Congenital myasthenic syndrome
Encyclopedia
Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction
. The effects of the disease are similar to Lambert-Eaton syndrome and Myasthenia gravis
, the difference being that CMS is not an autoimmune disorder.
.
Presynaptic symptoms include brief stops in breathing, weakness of the eye, mouth, and throat muscles. These symptoms often result in double vision and difficulty chewing and swallowing. Postsynaptic symptoms in infants include severe muscle weakness, feeding and respiratory problems, and delays in the ability to sit, crawl, and walk. Onset symptoms for all ages may include droopy eyelids
. A particular form of postsynaptic CMS (slow-channel CMS) includes severe weakness beginning in infancy or childhood that progresses and leads to loss of mobility and respiratory problems in adolescence or later life. Synaptic symptoms include early childhood feeding and respiratory problems, reduced mobility, curvature of the spine, and weakness, which causes a delay in motor milestones.
, treatments used in MG are not useful in CMS. MG is treated with immunosuppressant
s, but the effects of CMS are not caused by the immune system, it is hereditary.
A form of presynaptic CMS is caused by an insufficient release of acetylcholine
(ACh) and is treated with cholinesterase inhibitors. Postsynaptic fast-channel CMS (ACh receptors do not stay open long enough) is treated with cholinesterase inhibitors and 3,4-diaminopyridine
. Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which plugs the ACh receptor. Synaptic CMS has no effective drug treatment.
Low dose treatment with Ephedrine Sulphate has been shown to give some patients temporary improvement in strength. The Ephedrine
loses its effectiveness over the course of a few weeks. Once the patient has been off Ephedrine treatment for a few days, the treatment cycle can continue.
Oral doses of the drug Salbutamol
(Albuterol)have also shown to be effective in treating symptoms of CMS associated to mutations in Dok-7
. Typical dosage is 2 mg, three times per day.
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
. The effects of the disease are similar to Lambert-Eaton syndrome and Myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, the difference being that CMS is not an autoimmune disorder.
Symptoms and categories
The types of CMS are classified into three categories: presynaptic, postsynaptic, and synapticSynaptic
Synaptic may refer to:*Synapse, part of the nervous system*Synapsis, the pairing of two homologous chromosomes*Synaptic , a Linux graphical package management program for APT See also...
.
Presynaptic symptoms include brief stops in breathing, weakness of the eye, mouth, and throat muscles. These symptoms often result in double vision and difficulty chewing and swallowing. Postsynaptic symptoms in infants include severe muscle weakness, feeding and respiratory problems, and delays in the ability to sit, crawl, and walk. Onset symptoms for all ages may include droopy eyelids
Ptosis (eyelid)
Ptosis is a drooping of the upper or lower eyelid. The drooping may be worse after being awake longer, when the individual's muscles are tired. This condition is sometimes called "lazy eye", but that term normally refers to amblyopia...
. A particular form of postsynaptic CMS (slow-channel CMS) includes severe weakness beginning in infancy or childhood that progresses and leads to loss of mobility and respiratory problems in adolescence or later life. Synaptic symptoms include early childhood feeding and respiratory problems, reduced mobility, curvature of the spine, and weakness, which causes a delay in motor milestones.
Treatment
Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravisMyasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, treatments used in MG are not useful in CMS. MG is treated with immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
s, but the effects of CMS are not caused by the immune system, it is hereditary.
A form of presynaptic CMS is caused by an insufficient release of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
(ACh) and is treated with cholinesterase inhibitors. Postsynaptic fast-channel CMS (ACh receptors do not stay open long enough) is treated with cholinesterase inhibitors and 3,4-diaminopyridine
3,4-Diaminopyridine
3,4-Diaminopyridine is an organic compound with the formula C5H3N2. It is formally derived from pyridine by substitution of the 3 and 4 positions with an amino group....
. Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which plugs the ACh receptor. Synaptic CMS has no effective drug treatment.
Low dose treatment with Ephedrine Sulphate has been shown to give some patients temporary improvement in strength. The Ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
loses its effectiveness over the course of a few weeks. Once the patient has been off Ephedrine treatment for a few days, the treatment cycle can continue.
Oral doses of the drug Salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
(Albuterol)have also shown to be effective in treating symptoms of CMS associated to mutations in Dok-7
Dok-7
Dok-7 is a non-catalytic cytoplasmic adaptor protein that is expressed specifically in muscle and is essential for the formation of neuromuscular synapses. Further, Dok-7 contains pleckstrin homology and phosphotyrosine-binding domains that are critical for Dok-7 function...
. Typical dosage is 2 mg, three times per day.