Congenital myasthenic syndrome

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Classification according to ICD-10
G70 * Myasthenia gravis and other neuromuscular diseases
GG70.2 * Congenital or developmental myasthenia
ICD-10 online (WHO version 2019)

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

The congenital myasthenic syndrome, like myasthenia gravis , neonatal myasthenia and Lambert-Eaton-Rooke syndrome, belong to the myasthenic syndrome.

frequency

The frequency of occurrence is estimated at around 1: 500,000 and is significantly lower than, for example, myasthenia gravis (1: 5000). Worldwide there are 2000–3000 genetically confirmed cases and an additional just as many without genetic confirmation.

Cause and development of the disease

The disease is genetic , in contrast to autoimmune myasthenia gravis. Most forms occur sporadically and are both autosomal - recessive , and autosomal dominant inherited. Slow Channel Syndrome, in particular, occurs primarily in the family and is inherited in an autosomal dominant manner. In addition, there are new mutations to an unknown extent .

Signal transmission between nerve and muscle at the motor end plate is disturbed , either presynaptic, synaptic or postsynaptic.

complaints

The congenital myasthenic syndrome comprises disorders of several structures or at least 14 genes . A certain gene can in turn be disrupted in numerous places. Even with the same genetic defect, the severity of the symptoms can differ considerably without the cause being known.

What they all have in common is a premature fatigue of the skeletal muscles, i.e. the lids ( ptosis ), eye movers ( squinting , double vision ), facial muscles (expressionless face, saliva ), throat (drinking weakness or swallowing disorder , weak voice ), breathing muscles ( respiratory paralysis ), trunk and / or extremities ( delayed motor development , muscle weakness, paralysis ). In most patients, not all of the muscle groups mentioned are affected.

The weakness is particularly evident in the evening and after exercise. For many there are intermittent deteriorations (crises) with infections or excitement. The symptoms begin in the womb or in the first few months of life, rarely not until adolescence or adulthood ( congenital means congenital). The severity of the complaints ranges from hardly noticeable to being able to carry out everyday activities, but not for sports, to requiring a wheelchair or nocturnal home ventilation. Some have a progressive course over months to decades. However, the vast majority of patients can walk.

diagnosis

The diagnosis is made through anamnesis and examination , followed by serological diagnostics to rule out myasthenia gravis and the often pioneering neurophysiology (repetitive stimulation). Treatment with a cholinesterase inhibitor can then be attempted . Depending on the response, the genes or subforms in question can be narrowed down further. Genetic analyzes can predict which drugs are dangerous and which are likely to be beneficial. Muscle biopsies are physiologically examined in only a few centers worldwide.

treatment

In most cases there is the possibility of treatment with medication (the cholinesterase inhibitor pyridostigmine , 3, 4-diaminopyridine , ephedrine or salbutamol , fluoxetine , quinidine ). Often the symptoms are only partially improved and in some cases not at all.

In addition, physiotherapy , speech therapy , ventilation , the provision of aids , genetic counseling and training for relatives and patients can be used.

In addition to interactions with the drugs used, a worsening of the myasthenic syndrome (myasthenia gravis as well as congenital myasthenes syndrome) due to some drugs or substances (including tonic water and magnesium) must be considered.

literature

  • Andrew Engel: Myasthenia Gravis and Myasthenic Disorders. Oxford University Press, New York, 2012, ISBN 978-0-19-973867-0
  • Felix Jerusalem, Stefan Zierz: muscle diseases . Thieme Stuttgart 2003, ISBN 3-135-67803-2

Web links

Individual evidence

  1. ↑ /www.orpha.net: * Myasthenic syndromes, congenital here online * Myasthenia gravis here online
  2. ↑ a b U. Schara, A. Della Marina, A. Abicht: Congenital myasthenic syndromes: current diagnostic and therapeutic approaches. In: Neuropediatrics. Volume 43, Number 4, August 2012, pp. 184-193, ISSN  1439-1899 . doi : 10.1055 / s-0032-1323850 . PMID 22911480 . (Review).
  3. ↑ a b Congenital Myasthenic Syndromes Abicht A, Müller JS, Lochmüller H. 2003 May 9 (Updated 2012 Jun 28). In: Pagon RA, Bird TD, Dolan CR, et al., Editors. GeneReviews ™ (Internet). Seattle (WA): University of Washington, Seattle; 1993-. Retrieved February 16, 2013.
  4. ^ WL Yeung, CW Lam, PC Ng: Intra-familial variation in clinical manifestations and response to ephedrine in siblings with congenital myasthenic syndrome caused by novel COLQ mutations. In: Developmental Medicine and Child Neurology . Volume 52, number 10, October 2010, pp. E243 – e244, ISSN  1469-8749 . doi : 10.1111 / j.1469-8749.2010.03663.x . PMID 20370815 .
  5. ^ Congenital myasthenic syndromes (CMS) . Muscle Dystrophy Association - Romania . February 4, 2010. Retrieved February 16, 2013.
  6. ↑ Andrew Engel: Myasthenia Gravis and Myasthenic Disorders. Oxford University Press, New York, 2012, ISBN 978-0-19-973867-0 , pp. 174-181.
  7. ^ S1- Myasthenia Gravis guideline of the German Society for Neurology (DGN). In: AWMF online (as of 2008)
  8. ↑ Myasthenia Gravis Foundation of America (PDF; 246 kB)