Prenatal phenotype of FBXL4‐associated encephalomyopathic mitochondrial DNA depletion syndrome‐13

Abstract FBXL4 ‐associated encephalomyopathic mitochondrial DNA depletion syndrome‐13 (MTDPS13) is a rare genetic disorder characterized by early neonatal onset of encephalopathy, seizures, lactic acidosis, hypotonia, dysmorphism, and severe global developmental delay. Prenatal phenotype of molecularly confirmed MTDPS13 has not been well studied. This is the case report of a non‐consanguineously conceived fetus ascertained first at 20 weeks of gestation with multiple soft markers. Follow‐up fetal ultrasonogram at 26 weeks revealed periventricular cysts, periventricular echogenicity, ventriculomegaly, thin corpus callosum, mega cisterna magna, and large cavum. Fetal MRI confirmed these findings. Postnatally, the baby had clinical and biochemical findings indicative of a mitochondriopathy and died on neonatal day 3. Whole exome sequencing on stored amniotic fluid DNA confirmed the diagnosis of encephalomyopathic mitochondrial DNA depletion syndrome‐13 (MTDPS13). This report presents the prenatal phenotype of this rare mitochondriopathy, which has been recognized primarily in postnatal patients. The brain imaging findings in the reported fetus indicate that MTDPS13 is associated with progressive neurological involvement and brain tissue destructive changes starting as early as the second trimester of pregnancy. The case also raises concerns regarding the association of so‐called soft markers, which were the only initial finding in this case, with severe monogenic diseases.