Congenital myasthenic syndrome

Congenital myasthenic syndrome ( CMS abbreviation in English, synonym: congenital myasthenia ) is a very rare, heterogeneous group of inborn errors of signal transmission between nerve and muscle. This results in a load-dependent muscle weakness of the skeletal muscles.

Congenital myasthenic syndrome is as much as myasthenia gravis, neonatal myasthenia and Lambert -Eaton myasthenic syndrome to Rooke 's syndrome.

Frequency

The incidence is about 1: 500,000, for example, is estimated and compared to myasthenia gravis (1: 5000 ) is significantly lower. Worldwide there are 2000-3000 genetically confirmed cases and in addition as many without genetic confirmation.

Cause and pathogenesis

The disease is genetically determined, in contrast to autoimmune myasthenia gravis. Most forms occur sporadically and are both autosomal recessive and autosomal dominant inheritance. In particular, the slow channel syndrome occurs predominantly family and is inherited as an autosomal dominant trait. In addition, there are in an unknown extent before new mutations.

There will be a fault in the signal transmission between nerve and muscle at the motor end plate, either presynaptic, synaptic, or postsynaptic.

Discomfort

Congenital myasthenic syndrome includes several structures or disorders at least 14 genes. A gene can be disrupted at numerous points in turn. Even with identical genetic defect, the nature of the pain may vary materially, without knowing what would be known.

They all share a premature fatigability of skeletal muscles, so on eyelids (ptosis ), Augenbewegern ( strabismus, double vision ), mimic muscles ( expressionless face, drooling ), throat ( poor feeding or swallowing disorder, weak voice ), respiratory muscles ( respiratory paralysis ), trunk and / or extremities ( delayed motor development, muscle weakness, paralysis). In most patients, all of said muscle groups are not affected.

The weakness occurs mainly in the evening and after exercise in appearance. For many it comes to temporary deterioration ( crises ) with infection or excitement. The symptoms begin in the womb or early in life, often only in youth or adulthood ( congenital means congenital). The nature of the pain ranges from barely detectable over capable of the activities of daily living, but not to sports, to the wheelchair or nocturnal home ventilation requirement. In some, there is a progressive over months to decades course. The vast majority of patients can walk.

Diagnosis

The diagnosis is made by history and physical examination, followed by serological diagnosis to rule out myasthenia gravis and often groundbreaking neurophysiology ( repetitive stimulation). Subsequently, a treatment can be attempted with a cholinesterase inhibitor. Depending on the response, the genes in question or subtypes can be further limited. Genetic analysis can predict which drugs are dangerous and which probably beneficial. In only a few centers worldwide muscle biopsies are physiologically investigated.

Treatment

There is the possibility of treatment with medications ( the cholinesterase inhibitor pyridostigmine, 3, 4 -diaminopyridine, ephedrine or salbutamol, fluoxetine, quinidine) in most cases. Often the symptoms are only partly relieved and in some cases not at all.

In addition, physical therapy, speech therapy, mechanical ventilation, the provision of aids, genetic counseling and family or patient education can be used.

In addition to interactions with the medications used in the project is a deterioration of the myasthenic syndrome ( myasthenia gravis Congenital myasthenic syndrome as well as ) by some medications or substances (including tonic water and magnesium) to be observed.