The Contribution of Genetic Counseling to the Management of Childhood Epilepsies

The recent advances have shown that a large number of epilepsies are related to a monogenic cause that is to say that a deleterious variant affecting a single gene is strongly associated with the occurrence of the disease. This is especially true when seizures begin early in life, before the age of 1 years or even 3 months and is associated with other neurological (intellectual disability, autism) or extra neurological features. For example, more than a hundred genes are involved in the so-called developmental epileptic encephalopathy. The growing role of genetic testing, particularly since the transfer of high-throughput sequencing to diagnostics, has brought an etiological diagnosis in an increasing number of patients. Genetic confirmation may, in certain cases, provide prognostic or clues for therapeutic adaptation. It also provides genetic counseling to patients and their families. The risk of transmission within the family or of recurrence for a couple is dependent on the mode of transmission. In the field of childhood epilepsies, all modes of Mendelian transmission may be observed (X-linked, autosomal dominant or recessive) along with other modes of transmissions (chromosomal translocations, heredity of the mitochondrial genome). In the case of epileptic encephalopathies, many mutations occur de novo (they are not found in blood deoxyribonucleic acid from the parents). In these cases, the risk of transmission in the family is limited for relatives, but it cannot be considered as null for a future child of the couple (for each parent, even if they are separated) because germinal mosaic cannot be excluded. Accurate genetic counseling allows the couples at risk to benefit from prenatal or preimplantation diagnosis. Some phenomena may, however, complicate genetic counseling, such as incomplete penetrance or variability of expressivity, which can be observed in some forms of epilepsy with autosomal dominant inheritance, such as the genetic epilepsies with febrile seizures plus.

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