Congenital Myasthenic Syndromes
Description
Congenital Myasthenic Syndromes (CMS) are a group of rare, inherited disorders affecting the transmission of nerve impulses to muscles. This results in varying degrees of muscle weakness and fatigue, often present at birth or in early childhood. While there is no cure for CMS, effective treatments and management strategies can help individuals live fulfilling lives.
Genes Involved
Over 20 genes have been linked to CMS. Some of the most commonly affected genes include:
- CHRNE: Codes for the epsilon subunit of the acetylcholine receptor (AChR)
- CHRND: Codes for the delta subunit of the AChR
- DOK7: Codes for a protein that helps anchor the AChR to the muscle cell membrane
- RAPSN: Codes for a protein involved in the formation of neuromuscular junctions
- MUSK: Codes for a protein essential for AChR clustering at the neuromuscular junction
Recognizing the Signs and Symptoms
The signs and symptoms of CMS vary widely depending on the specific type. Common symptoms include:
- Muscle weakness: This can affect any muscle group, but is often seen in the face, eyelids, neck, limbs, and respiratory muscles.
- Fatigue: Easily tiring out during physical activity or even everyday tasks.
- Difficulty breathing: This can range from mild shortness of breath to respiratory failure in severe cases.
- Drooling: Due to weakness in facial muscles.
- Feeding difficulties: In infants, weak sucking and swallowing muscles can lead to problems with feeding.
- Delayed motor milestones: Infants with CMS may have difficulty achieving milestones like rolling over, sitting up, or walking.
- Double vision (diplopia): Weakness in eye muscles can cause blurred or double vision.
Causes
CMS is caused by genetic mutations that disrupt the communication between nerves and muscles at the neuromuscular junction. This disruption can occur in several ways:
- Defective acetylcholine receptors (AChRs): Mutations in the genes encoding AChR subunits lead to faulty receptors that cannot bind acetylcholine effectively. This results in reduced nerve signal transmission.
- Reduced AChR numbers: Mutations in genes like DOK7, RAPSN, and MUSK can affect the number and clustering of AChRs at the neuromuscular junction, leading to impaired signal transmission.
- Problems with acetylcholine production or breakdown: Some mutations affect the production or breakdown of acetylcholine, the neurotransmitter responsible for muscle contraction.
Inheritance/recurrence risk
CMS is usually inherited in an autosomal recessive pattern, meaning both parents must carry the faulty gene for their child to inherit the disorder. In some cases, the inheritance pattern may be autosomal dominant.
If both parents are carriers, there is a 25% chance their child will inherit CMS, a 50% chance their child will be a carrier, and a 25% chance their child will not inherit the gene.
