Mitochondrial POLG related disorder presenting prenatally with fetal cerebellar growth arrest

Michal Inbar-Feigenberg; Susan Blaser; Cynthia Hawkins; Patrick Shannon; Stacy Hewson; David Chitayat

doi:10.1007/s11011-018-0218-2

Mitochondrial POLG related disorder presenting prenatally with fetal cerebellar growth arrest

Metab Brain Dis. 2018 Aug;33(4):1369-1373. doi: 10.1007/s11011-018-0218-2. Epub 2018 Mar 25.

Authors

Michal Inbar-Feigenberg¹, Susan Blaser², Cynthia Hawkins³, Patrick Shannon⁴, Stacy Hewson⁵, David Chitayat^{5

6}

Affiliations

¹ Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. michal.inbar-feigenberg@sickkids.ca.
² Department of Diagnostic Imaging, Division of Neuroradiology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
³ Department of Paediatric Laboratory Medicine, Division of Neuropathology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁴ Department of Pathology & Lab Medicine, Division of Neuropathology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁵ Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁶ The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

PMID: 29574624
DOI: 10.1007/s11011-018-0218-2

Abstract

We report the prenatal findings of severe cerebellar growth arrest in two siblings with POLG1 mutations. The first presented with seizures and lactic acidosis immediately after premature birth and was diagnosed with mitochondrial disease on muscle biopsy. Molecular DNA analysis confirmed homozygous missense mutation in the POLG1 gene. The pregnancy of the second sibling was monitored closely by repeat fetal ultrasounds since the parents declined invasive testing. A detailed fetal ultrasound at 19 weeks gestation showed a small cerebellum with transcerebellar diameter (TCD) on axial cranial imaging, measuring below the 5th centile for gestational age. Molecular analysis confirmed the same homozygous familial mutation in the POLG1gene. This report further delineates the phenotypic features of the POLG related disorders and expands it to the prenatal era. Subsequent pregnancies were monitored by molecular analysis, using chorionic villus sampling (CVS).

Keywords: Cerebellar growth arrest; Fetal; MRI; Mitochondrial disorder; POLG related disorders; Polymerase gamma (POLG1) gene; Prenatal diagnosis.

Publication types

Case Reports

MeSH terms

Cerebellar Diseases / diagnostic imaging
Cerebellar Diseases / genetics*
DNA Polymerase gamma / genetics*
Humans
Infant, Newborn
Male
Mitochondria / genetics*
Mitochondrial Diseases / diagnostic imaging
Mitochondrial Diseases / genetics*
Mutation, Missense*
Ultrasonography, Prenatal

Substances

DNA Polymerase gamma
POLG protein, human