Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency

Authors

Olivier Fortin, Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA, 20010.
Kelsey Christoffel, Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA, 20010.
Abdullah Shoaib, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA, 75235.
Charu Venkatesan, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA, 45229.
Kate Cilli, Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA, 20010.
Jason W. Schroeder, Department of Radiology, Children's National Hospital, Washington, District of Columbia, USA, 20010.
Cesar Alves, Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA, 02115.
Rebecca D. Ganetzky, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA, 19104.
Jamie L. Fraser, Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA, 20010.

Document Type

Journal Article

Publication Date

4-10-2024

Journal

medRxiv : the preprint server for health sciences

DOI

10.1101/2024.04.08.24303574

Keywords

Fetal imaging; Fetal neurogenetics; Metabolic disorders; Mitochondrial disorders; Prenatal genetic testing

Abstract

Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including . Typical neonatal brain imaging findings in PDCD have been described, with a focus on malformative features and chronic encephaloclastic changes. However, fetal brain MRI imaging in confirmed PDCD has not been comprehensively described. We sought to demonstrate the prenatal neurological and systemic manifestations of PDCD determined by comprehensive fetal imaging and genomic sequencing. All fetuses with a diagnosis of genetic PDCD who had undergone fetal MRI were included in the study. Medical records, imaging data, and genetic testing results were reviewed and reported descriptively. Ten patients with diagnosis of PDCD were included. Most patients had corpus callosum dysgenesis, abnormal gyration pattern, reduced brain volumes, and periventricular cystic lesions. One patient had associated intraventricular hemorrhages. One patient had a midbrain malformation with aqueductal stenosis and severe hydrocephalus. Fetuses imaged in the second trimester were found to have enlargement of the ganglionic eminences with cystic cavitations, while those imaged in the third trimester had germinolytic cysts. Fetuses with PDCD have similar brain MRI findings to neonates described in the literature, although some of these findings may be subtle early in pregnancy. Additional features, such as cystic cavitations of the ganglionic eminences, are noted in the second trimester in fetuses with PDCD, and these may represent a novel early diagnostic marker for PDCD. Using fetal MRI to identify these radiological hallmarks to inform prenatal diagnosis of PDCD may guide genetic counseling, pregnancy decision-making, and neonatal care planning.

APA Citation

Fortin, Olivier; Christoffel, Kelsey; Shoaib, Abdullah; Venkatesan, Charu; Cilli, Kate; Schroeder, Jason W.; Alves, Cesar; Ganetzky, Rebecca D.; and Fraser, Jamie L., "Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency" (2024). GW Authored Works. Paper 4737.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4737

Department

Radiology