Infantile epileptic spasms syndrome in a child with lissencephaly associated with de novo PAFAH1B1 variant and coincidental CMV infection

Type 1 lissencephaly is a brain malformation characterized by agyria and pachygyria and is known to be caused by congenital infections and genetic variations. Here we present a case of a 4-month-old female with new onset infantile epileptic spasms syndrome (IESS) with initial etiology concerned for congenital cytomegalovirus (cCMV) due to a positive urine CMV PCR and maternal viral syndrome during pregnancy. Her brain MRI was significant for type 1 lissencephaly without other radiographical features of cCMV. The patient initially responded to high dose Prednisolone but had relapse of spasms at 9-month-old and required an ACTH course. She later developed generalized tonic seizures and focal impaired awareness seizures. Subsequent whole exome sequencing (WES) trio revealed a de novo PAFAH1B1 (c.405G > A, p.W135*) heterozygous nonsense variant which is pathogenic and thus solved the diagnostic puzzle. This case demonstrates that the absence of cCMV stigmata should raise concern for alternative etiology in cases of lissencephaly and the importance of genetic evaluation for subsequent management and family counseling.