Periventricular Heterotopia and Novel FLNA Gene Variant: Clinical and Neuroimaging Clues for an Early Diagnosis

Abstract

Pathogenic variants in the X-linked FLNA gene encoding filamin A cause a wide range of manifestations, such as periventricular nodular heterotopia (PNH), cardiovascular malformations, connective tissue disorders, and pulmonary involvement with progressive lung disease and variable clinical outcomes ranging from lung transplantation to death. We report a case of a term female newborn with patent ductus arteriosus (PDA) and unexplained respiratory distress in whom cranial ultrasound (cUS) was suggestive of PNH. Brain magnetic resonance imaging confirmed PNH and FLNA gene analysis identified a novel heterozygous pathogenic variant, c.3951C>G (p.Tyr1317Ter). She had complete resolution of her respiratory disease and spontaneous closure of her ductus arteriosus around 10 months. Since then, she developed chronic constipation and joint hypermobility. Early recognition of cUS clues for PNH, associated with PDA and pulmonary involvement in a female newborn, guided genetic testing, allowing for a correct diagnosis and multidisciplinary surveillance of this heterogeneous disorder. We also highlight the good clinical outcome concerning lung involvement in contrast with cases reported in the literature.