Clinical review of genetic epileptic encephalopathies

Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered.

► Work-up should include basic metabolic tests, brain MRI/MRS, and neuro-ophthalmology exam. ► Neonates with intractable seizures should have a trial of pyridoxine, folinic acid, and pyridoxal phosphate. ► Array CGH is helpful in detecting chromosomal causes of epilepsy. ► Specific gene sequencing can be useful if there are no CNVs and metabolic causes.