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Mitochondrial POLG related disorder presenting prenatally with fetal cerebellar growth arrest

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A Commentary to this article was published on 01 May 2018

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).

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Authors and 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, Stacy Hewson & David Chitayat

  2. Department of Diagnostic Imaging, Division of Neuroradiology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Susan Blaser

  3. Department of Paediatric Laboratory Medicine, Division of Neuropathology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Cynthia Hawkins

  4. Department of Pathology & Lab Medicine, Division of Neuropathology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    Patrick Shannon

  5. The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    David Chitayat

Authors
  1. Michal Inbar-Feigenberg
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  2. Susan Blaser
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  3. Cynthia Hawkins
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  4. Patrick Shannon
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  5. Stacy Hewson
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  6. David Chitayat
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Corresponding author

Correspondence to Michal Inbar-Feigenberg.

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Written consent for this report was obtained from the family in compliance with the Hospital for Sick Children Research Ethics Board guidelines.

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The authors declare that they have no conflict of interest.

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Inbar-Feigenberg, M., Blaser, S., Hawkins, C. et al. Mitochondrial POLG related disorder presenting prenatally with fetal cerebellar growth arrest. Metab Brain Dis 33, 1369–1373 (2018). https://doi.org/10.1007/s11011-018-0218-2

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  • DOI: https://doi.org/10.1007/s11011-018-0218-2

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