Gamstorp Disease; Adynamia Episodica Hereditaria With Myotonia; Adynamia Episodica Hereditaria Without Myotonia; Normokalemic Periodic Paralysis; Sodium Channel Muscle Disease

Hyperkalemic periodic paralysis is characterized by attacks of flaccid limb weakness, which may be accompanied by weakness of the eyes, throat and trunk. During attacks, serum potassium concentration is >5 mmol/L or has increased by at least 1.5 mmol/L over baseline. Muscle strength and serum postassium concentration are normal between attacks. Onset is generally before 20 years of age.

SCN4A is the only gene identified to date that is known to be associated with hyperkalemic periodic paralysis. Four recurrent mutations account for almost all of the SCN4A disease alleles; together these account for approximately 55% of cases.

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of hyperkalemic periodic paralysis.
2. Prenatal testing (technically feasible but not routinely performed – contact MGL to discuss):
   1. Pregnancies known to be at risk of hyperkalemic periodic paralysis and the SCN4A mutation is known.
3. Presymptomatic testing:
   1. Asymptomatic children and adults at risk of this condition because of a family history. The SCN4A mutation must be known.

Bidirectional Sanger sequencing of SCN4A exons 13 and 24 and their flanking intronic sequences, which encompass the four common mutations associated with hyperkalemic periodic paralysis: c.2065C>A (p.Leu689Ile), c.2078T>C (p.Ile693Thr), c.2111C>T (p.Thr704Met) and c.4774A>G (p.Met1592Val).

NM_000334.4 The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., mutations outside the regions tested as described above, large genomic deletions, promoter mutations, regulatory element mutations).

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In rare cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.