A retrospective study on the efficacy of prenatal diagnosis for pregnancies at risk of mitochondrial DNA disorders



Prenatal diagnosis of mitochondrial DNA (mtDNA) disorders is challenging due to potential instability of fetal mutant loads and paucity of data connecting prenatal mutant loads to postnatal observations. Retrospective study of our prenatal cohort aims to examine the efficacy of prenatal diagnosis to improve counseling and reproductive options for those with pregnancies at risk of mtDNA disorders.


We report on a retrospective review of 20 years of prenatal diagnosis of pathogenic mtDNA variants in 80 pregnant women and 120 fetuses.


Patients with undetectable pathogenic variants (n = 29) consistently had fetuses free of variants, while heteroplasmic women (n = 51) were very likely to transmit their variant (57/78 fetuses, 73%). In the latter case, 26 pregnancies were terminated because fetal mutant loads were >40%. Of the 84 children born, 27 were heteroplasmic (mutant load <65%). To date, no medical problems related to mitochondrial dysfunction have been reported.


Placental heterogeneity of mutant loads questioned the reliability of chorionic villous testing. Fetal mutant load stability, however, suggests the reliability of a single analysis of amniotic fluid at any stage of pregnancy for prenatal diagnosis of mtDNA disorders. Mutant loads under 40% reliably predict lack of symptoms in the progeny of heteroplasmic women.

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Fig. 1: Distribution of fetal mutant loads.
Fig. 2: Maternal factors and fetal mutant loads.

Data availability

Protocols for quantification of each mtDNA variant and reagents are available on request.


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We thank participating families for their cooperation and the physicians involved for care provided to couples. Research was supported by grants from the Association Française contre les Myopathies (AFM) and the French Agence de la Biomédecine (ABM). The authors thank Jason Miller, who edited the manuscript for style and grammar.


The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Author information




Conceptualization: J.-P.B., A.M., A.R. Data curation: J.B., R.B., S.M., J.S. J.-P.B., A.M. Formal analysis: M.M., Z.A., N.G., G.B. Investigation: Y.V., L.S., B.B., J.M. Methodology: J.S., S.M., A.M., J.-P.B. Writing—original draft: J.S, JP.B, A.M. Writing—review and editing: J.S., A.M.

Corresponding author

Correspondence to Julie Steffann MD, PhD.

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The authors declare no competing interests.

Ethics Declaration

This retrospective review has been approved by the Research Ethics Committee of the Necker-Enfants Malades University Hospital (IRB registration 00011928). All experiments were performed in accordance with relevant guidelines and French regulations. The Necker-Enfants Malades University Hospital has a general privacy statement informing patients that their data can be used for scientific research (https://www.aphp.fr/protection-des-donnees-personnelles).

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Steffann, J., Monnot, S., Magen, M. et al. A retrospective study on the efficacy of prenatal diagnosis for pregnancies at risk of mitochondrial DNA disorders. Genet Med (2020). https://doi.org/10.1038/s41436-020-01043-3

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