The Invitae Hyperkalemic Periodic Paralysis Test analyzes the SCN4A gene. Hyperkalemic periodic paralysis (HYPP) is characterized by muscle weakness and/or paralysis accompanied by normal to high levels of serum potassium.
Individuals with clinical signs and symptoms of HYPP may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance or help determine which relatives are at risk.
Hyperkalemic periodic paralysis (HYPP), part of a group of disorders known as channelopathies, is characterized by episodes of muscles weakness with normal to high serum potassium concentration. Episodes can be provoked or worsened by potassium intake. There is variability in age of onset, but the first attack generally occurs before the age of 10 years, and episodes generally increase in frequency and intensity until approximately 50 years of age, after which they tend to decrease. In approximately half of the individuals affected with HYPP, mild muscle stiffness (myotonia) occurs between attacks. More than 80% of affected individuals develop fixed or chronic progressive weakness that results in significant disability in later adulthood.
The SCN4A gene is also associated with paramyotonia congenita, potassium-aggravated myotonia, and hypokalemic periodic paralysis (HOKPP). There is significant clinical overlap between these conditions.
SCN4A is the only gene known to be associated with HYPP. The proportion of cases of HYPP attributed to pathogenic variants in SCN4A is 80%.
HYPP is inherited in an autosomal dominant manner.
The penetrance of HYPP is higher than 90% although some variants show reduced penetrance with no clinically detectable symptoms.
The prevalence of HYPP is approximately 1.7 out of every 1,000,000 individuals.
Genetic testing for HYPP may confirm a suspected diagnosis and help inform recurrence risk and accurate medical management.
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|