Congenital Myasthenic Syndromes (CMS) is the name for a group of inherited disorders of the neuromuscular junction which have certain clinical and genetic features in common. Muscle weakness is common in CMS, but highly variable from hour to hour, day to day or month to month. Many patients with CMS can be effectively treated with a standard medication. CMS is a rare condition with approximately 1 patient in 150,000 people world-wide.
First symptoms of CMS usually occur in children before the age of 3 years, but a later onset has also been observed in some patients. In infancy floppiness, poor suck and cry, choking spells, breathing difficulties and hanging eye lids (ptosis) are frequently observed. Symptoms worsen by crying or activity. Children often show delayed motor milestones and may have difficulty running. They may struggle climbing stairs and fatigue quickly on exertion. They may easily tire in PE or other sports, and often show ptosis, and some have an inability to move their eyes, may develop spinal deformities and have reduced muscle bulk. The heart muscle is usually not affected. Breathing difficulties can become very severe in some patients requiring assisted ventilation. Illnesses, anaesthetics and a wide range of drugs may lead to worsening of CMS symptoms.
The inheritance of CMS is autosomal recessive in the majority of patients. Both parents are usually unaffected, but pass on a defective copy of the CMS gene to their affected child. Mutations in at least 15 different genes can cause CMS, the most frequent gene in CMS is CHRNE (gene coding for the epsilon subunit of the acetylcholine receptor). Mutations are spread across the entire length of the gene, but some mutations are recurring in certain populations, so-called founder mutations. Therefore, several genes should be analysed for mutations by sequencing if CMS is clinically suspected. Rarely, CMS are inherited in dominant traits (slow-channel syndromes).
CMS genes code for proteins that are involved in neuromuscular transmission, the process involved in transmitting signals, that originate in the brain, from the nerve endings to the muscle. This is a crucial step in relaying the signals to muscles to contract or relax. Drugs that influence neuromuscular transmission can result in clear improvement in patients with CMS and are prescribed by specialists. However, not every CMS patient responds favourably to the same drug and some patients may get worse with a medication that helps others. Securing a genetic diagnosis helps choosing the appropriate medication for the individual patient. Unlike in Myasthenia Gravis, which is an autoimmune disorder, corticosteroids, immunosuppressive drugs or removal of the thymus gland do not provide benefit to CMS patients.