Congenital Myopathy Panel (14 Genes) Test Details
Congenital myopathies are a group of rare muscle diseases that tend to present at birth or in childhood with hypotonia or muscle weakness, often accompanied with respiratory insufficiency and/or feeding difficulty. They generally result from genetic defects in structural components of the muscle contractile apparatus and are nonprogressive. Congenital myopathies are grouped based on characteristic histopathological alterations observed in muscle biopsies, such as the presence of nemaline rods in nemaline myopathy, increase in internalized nuclei in centronuclear myopathy, and areas devoid of oxidative enzyme activity in central core/multiminicore diseases. The estimated combined incidence of congenital myopathies ranges from 1/25,000 to 1/150,000, with each subtype accounting for a small proportion of cases. Congenital myopathies can be inherited in an autosomal recessive, autosomal dominant, or X-linked manner. Please visit GeneReviews for more information about specific types of congenital myopathies.
Current tests for Congenital Myopathy
Congenital Myopathy Panel - 14 genes
Read More for expanded gene table.Read More...
|ACTA1||Actin, Alpha, Skeletal Muscule 1||102610||1q42.13|
|BIN1||Briding Integrator 1||601248||2q14.3|
|MYH7||Myosin, Heavy Chain 7, Cardiac Muscle, Beta||160760||14q11.2|
|RYR1||Ryanodine Receptor 1||180901||19q13.2|
|SEPN1||Selenoprotein N, 1||606210||1p36.11|
|TNNT1||Troponin T1, Skeletal, Slow||191041||19q13.42|
The Congenital Myopathy Panel should be ordered for individuals with a clear diagnosis of congenital myopathy. This panel will provide comprehensive coverage of the implicated genes and minimize the incidence of variants of unknown significance compared with the MyoGene panel.
The MyoGene Panel is best suited for individuals who already have exhausted current testing options or those whose clinical diagnosis is not yet clear and may help shorten the “diagnostic odyssey.” While the MyoGene Panel offers comprehensive testing for multiple forms of myopathy, there is a higher likelihood of finding novel variants, which may be more difficult to interpret if it is found in a gene that is not (yet) known to cause the individual’s disease.
This test is performed by next generation sequencing using Agilent SureSelect capture followed by sequencing of the coding regions and splice sites using Illumina sequencing technologies. Variant calls are generated using the Burrows-Wheeler Aligner followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or an alternate assay. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions that could affect gene expression, aside from the splice junctions, and a few exons have been excluded due to technical difficulties. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.
The detection rate of the Congenital Myopathy Panel is approximately 25% (Amburgey 2011: PubMed ID 22028225).