Counseling
Mode of Inheritance
The disorder is not inherited, but rather results from de novo mutations or inheritance from an unaffected mosaic parent. Since affected individuals are heterozygotes, expression can be said to be autosomal dominant.
Risk to Family Members
Parent of a Proband
Two cases of inheritance from a somatic mosaic, unaffected parent have been reported. Therefore, molecular genetic testing is recommended for the parents of a proband with an apparent de novo pathogenic variant.
If the pathogenic variant found in the proband cannot be detected in leukocyte DNA of either parent, the most likely explanation is a de novo pathogenic variant in the proband; another possible explanation is germline mosaicism in a parent. The incidence of germline mosaicism is approximately 3%.
Sibs of a Proband
The risk to the sibs of the proband depends on the genetic status of the proband’s parents.
If the SCN8A pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is low but greater than that of the general population because of the possibility of germline mosaicism.
Offspring of a Proband
Individuals with SCN8A-related epilepsy typically do not reproduce. Because the disorder is dominant, each child of an individual with SCN8A-related epilepsy has a 50% chance of inheriting the pathogenic variant.
Other family members
The risk to other family members depends on the status of the proband's parents. If a parent is mosaic for the SCN8A pathogenic variant, his or her family members may be at risk.
Related Genetic Counseling Issues
Family Planning
The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
Prenatal Testing
Because the SCN8A pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at increased risk for SCN8A-related epilepsy may be available from a clinical laboratory that offers either testing of this gene or custom prenatal testing.
Preimplantation genetic diagnosis (PGD)
Preimplantation genetic diagnosis (PGD) for SCN8A-related epilepsy may be an option for some families in which the SCN8A pathogenic variant has been identified.