FOXG1 syndrome: genetic background revealed by trio WES in case of a critically ill neonate.

Abstract

FOXG1 syndrome, also referred to as congenital Rett syndrome, is an autosomal dominant neurodevelopmental disorder characterised by early-onset developmental delay, microcephaly, movement abnormalities, and epilepsy. We report a case of a male infant who presented with hypotonia and abnormal respiratory effort at birth. Due to the non-specific but serious clinical presentation, the infant underwent trio whole-exome sequencing (WES). WES-Trio revealed a de novo heterozygous frameshift mutation in FOXG1 (c.459_460delGG; p.Glu154Glyfs). Despite intensive care, the infant died within 24 hours of birth. This case description emphasises the importance of rapid clinical care through trio WES for ill neonates, where an accurate diagnosis was made possible by identifying a de novo pathogenic variant related to FOXG1 syndrome. Early genetic diagnoses for severe neonatal encephalopathy of otherwise unexplainable aetiology are noteworthy/critical in terms of management and prognosis, and importantly for parental counselling.