Genetic etiologies of neonatal seizures

Neonates presenting with seizures are frequently assessed and managed by neonatologists in the NICU. Although hypoxic-ischemic encephalopathy and infection are common underlying causes of neonatal seizures, many patients with neonatal epilepsy will have an identifiable genetic etiology. Often these cases will be evaluated in collaboration with a geneticist. The categories of genetic causes of neonatal seizures include 1) structural brain malformations; 2) inborn errors of metabolism; 3) syndromic; and 4) nonsyndromic, single gene. Evaluation of these patients involves a comprehensive history and examination, followed by appropriate investigations and diagnostic genetic testing. Components of the diagnostic process will vary based on the clinical suspicion and differential diagnoses. In certain cases, syndromic surveillance for evaluation of other congenital anomalies may be recommended. Determination of the underlying genetic diagnosis, when present, will have important implications for treatment. Targeted therapies are currently available for specific genetic syndromes, and outcomes may improve with earlier initiation of therapy. Certain genetic diagnoses may also have guideline-based management involving screening for other manifestations of the disorder.