Diffuse interstitial lung disease in a male fetus with periventricular nodular heterotopia and filamin A mosaic variant

Abstract

AbstractBackgroundMost 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.