Congenital myasthenia extended panel [29 genes]
Congenital myasthenia is a disease produced by a biochemical defect or a structural alteration of the neuromuscular junction that results in a clinical profile of feebleness and muscular fatigue from birth or early infancy. It is convenient to distinguish these forms of the disease from myasthenia gravis (of autoimmune origin) and the neonatal forms (in children of mothers who have myasthenia gravis).
The prevalence of congenital myasthenic syndromes is estimated to be between 1 in 500,000 (GeneReviews) and 9.2 in 1,000,000 (Parr et al., 2014). Their etiology is genetic in large part. As of today, several implicated genes are known, allowing for up to two thirds of cases to have a positive genetic diagnosis (Jacob et al., 2009).
The genes that are most frequently implicated and their yields are: CHRNE (50%), RAPSN (15-20%), COLQ (10-15%), DOK7 (10-15%), CHAT (5%), and GFPT1 (2%). We have included these six genes as part of the basic study, and we have also developed an extended panel of 29 related genes that will allow optimizing the diagnostic yield.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- Abicht A, Müller J S, Lochmüller H. Congenital Myasthenic Syndromes. 2003 May 9 [updated 2016 Jul 14]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
- Jacob S, Viegas S, Lashley D, Hilton-Jones D. Myasthenia gravis and other neuromuscular junction disorders. Pract Neurol. 2009 Dec;9(6):364-71.
- Parr JR, Andrew MJ, Finnis M, Beeson D, Vincent A, Jayawant S. How common is childhood myasthenia? The UK incidence and prevalence of autoimmune and congenital myasthenia. Arch Dis Child. 2014 Jun;99(6):539-42.