Diffuse Interstitial Lung Disease in a Male Fetus with Periventricular Nodular Heterotopia and Filamin A Mosaic Variant

BackgroundMost periventricular nodular heterotopias (PNHs) are associated with a mutation in the filamin A (FLNA) gene in Xq28. This condition is associated with cardiovascular malformations, connective tissue abnormalities, epilepsy, and intellectual deficiency of varying severity.Materials and MethodsWe report a new FLNA gene mutation in a male patient associated with PNH and diffuse interstitial lung disease.ResultsA 23-year-old woman was referred at 31 gestational weeks to evaluate a suspected mega cisterna magna and ventricular septal defect with atrioventricular valve alignment in a male fetus. The fetal magnetic resonance imaging showed PNH associated with corpus callosum dysgenesis and a mega cisterna magna. At 2 months of age, the infant was diagnosed with severe respiratory distress with hypoxemia. A chest CT scan demonstrated a diffuse interstitial lung pattern with emphysema, multiple atelectasis foci, and signs of pulmonary hypertension. Rapid worsening led to his death at 4 months. Targeted sequencing of the FLNA gene identified a de novo hemizygous variant in 75% mosaic in lymphocyte cells, resulting in incomplete FLNA function loss.Discussion & ConclusionOn the diagnosis of antenatal PNH, the possibility of such lung involvement should be considered in the prognostic evaluation during prenatal counseling. What is already known about this topic?Most periventricular nodular heterotopias (PNHs) are associated with a X-linked mutation in the filamin A (FLNA) gene.FLNA related PNH in female patients is associated with cardiovascular malformations, connective tissue abnormalities, epilepsy, and intellectual deficiency of varying severity.What does this study add?A mosaic loss-of-function FLNA mutation should be considered in male fetuses with PNH. FLNA related PNH can be associated with severe diffuse interstitial lung disease and pulmonary arterial hypertension.