The Invitae Periodic Paralysis Panel analyzes three genes associated with periodic paralysis, a disorder characterized by temporary episodes of muscle weakness or paralysis. These genes were curated based on current evidence to provide a comprehensive test for the genetic causes of periodic paralysis.
Individuals with clinical signs and symptoms of periodic paralysis may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance, help determine which relatives are at risk, or guide possible enrollment in clinical trials.
CACNA1S KCNJ2 SCN4A
CACNA1S KCNJ2 SCN4A
Periodic paralysis is a channelopathy characterized by episodes of muscle weakness. Periodic paralysis can be a primary condition or can occur as a feature of a larger syndrome. Primary periodic paralysis is associated with the CACNA1S and SCN4A genes. Frequency, duration and severity of the episodes are highly variable across affected individuals. Age of onset of first episode can be as early as the first year of life, or as late as 20 years of age. Symptoms improve with potassium intake. Myopathy, which can be mild or severe, develops in about 25% of affected individuals and occurs at variable ages. Individuals with periodic paralysis secondary to Andersen-Tawil syndrome, caused by mutations in the KCNJ2 gene, typically present with periodic paralysis together with ventricular arrhythmias and prolonged QT interval.
|Proportion of cases attributed to variants in the listed genes|
|KCNJ2||60% of Andersen-Tawil syndrome|
Periodic paralysis associated with the CACNA1S, KCNJ2 and SCN4A genes is inherited in an autosomal dominant manner.
The penetrance of CACNA1S-related periodic paralysis is up to 90% in males and can be as low as 50% in females depending on the variant. Penetrance of SCN4A-related periodic paralysis appears to be variant dependent; complete penetrance has been observed for certain variants, however in females, low penetrance has been observed for other variants. Andersen-Tawil syndrome demonstrates reduced penetrance and variable expressivity.
The prevalence of periodic paralysis is estimated to occur in 1 out of every 100,000 individuals. Andersen-Tawil syndrome is diagnosed in less than 10% of periodic paralysis cases.
Periodic paralysis is a clinically heterogeneous group of disorders. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform family planning.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|