Background: Non-febrile illness seizures may present in previously healthy children as afebrile seizures associated with minor infections, such as mild gastroenteritis or respiratory tract infections, and are linked to a genetic predisposition. For the novel human coronavirus SARS-CoV-2, causing COVID-19, fever, cough, and gastrointestinal complaints are the most common symptoms in children, and a hyperimmune response may be present. No detailed temporally associated neurological complications have been documented in pediatric case series so far. Case description: We present the case of a 3-months-old girl with non-febrile repeated seizures in a COVID-19 family setting. The infant started with a mild fever and cough that lasted for 2 days. At day 6 from onset, the girl presented with two focal motor seizures with impaired consciousness and awareness. All investigations ruled out signs of meningo-encephalitis or active epilepsy, including normal electroencephalogram and cerebral magnetic resonance imaging. PCR from nasal and throat swabs was positive for SARS-CoV-2. Remarkably, blood ferritin and D-dimer levels were increased. At day 9, the infant presented another afebrile motor seizure, and levetiracetam dose was modified there was a favorable response within 3 months of the follow-up. Much interest has been raised with regards to host genetic determinants to disease severity and susceptibility to COVID-19. We thus performed whole exome sequencing, revealing a pathogenic frameshift mutation in the PRRT2 gene in both the mother and the infant. The mother had presented two late infantile febrile convulsions with normal outcome afterwards. Discussion: The hyperimmune response described in adult cases with COVID-19 can be seen in infants, even in the absence of respiratory symptoms. Moreover, COVID-19 may present in infants as non-febrile seizures, triggering early onset seizures in infants with a genetic predisposition. In this pandemic situation, precision medicine using massive sequencing can shed light on underlying molecular mechanisms driving the host response to COVID-19.