Pitfalls of prenatal diagnosis associated with mosaicism

Kelly Reilly; Samantha Doyle; Susan J Hamilton; Mark D Kilby; Fionnuala Mone

doi:10.1111/tog.12850

Pitfalls of prenatal diagnosis associated with mosaicism

Kelly Reilly, Samantha Doyle, Susan J Hamilton, Mark D Kilby, Fionnuala Mone^*

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Review article › peer-review

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Abstract

Key content
- Fetal placental mosaicism, of which confined placental mosaicism is a subtype, occurs in 2–3% of pregnancies.
- Confined placental mosaicism may lead to a false positive result on non-invasive prenatal testing (NIPT) for common aneuploidies.
- The risk of mosaicism in a chorionic villus sample (CVS) following a positive NIPT result is 2, 4, 22 and 59% for trisomy 21, 18, 13 and 45, X respectively.
- Following a positive NIPT result in the absence of a significant fetal structural anomaly (FSA), care is required in selecting the optimal diagnostic invasive test. Discussion of the limitations and implications is essential and referral to clinical genetics may be warranted.

Learning objectives
- To understand the embryological causes for and types of fetal placental mosaicism.
- To appreciate underlying principles in NIPT and genomic testing strategies in relation to mosaicism.
- To follow suggested clinical management principles in relation to prenatal test counselling.

Ethical issues
- Clinicians face a dilemma following a high-risk NIPT result in the setting of normal ultrasound. Awaiting long-term culture, as opposed to short-term culture on CVS, or amniocentesis delays potential termination of pregnancy.
- Sex chromosome abnormalities on NIPT without an identifiable FSA cannot be interpreted reliably. Hence, NIPT should not be offered for sex chromosome aneuploidy.

Original language	English
Number of pages	10
Journal	The Obstetrician and Gynaecologist
Early online date	20 Dec 2022
DOIs	https://doi.org/10.1111/tog.12850
Publication status	Early online date - 20 Dec 2022

Keywords

exome sequencing
microarray
fetus
Mosaicism
NIPT
Fetal Diseases

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10.1111/tog.12850Licence: CC BY

Pitfalls of prenatal diagnosis associated with mosaicism
Copyright 2022 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 581 KBLicence: CC BY

Cite this

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title = "Pitfalls of prenatal diagnosis associated with mosaicism",

abstract = "Key content- Fetal placental mosaicism, of which confined placental mosaicism is a subtype, occurs in 2–3% of pregnancies.- Confined placental mosaicism may lead to a false positive result on non-invasive prenatal testing (NIPT) for common aneuploidies.- The risk of mosaicism in a chorionic villus sample (CVS) following a positive NIPT result is 2, 4, 22 and 59% for trisomy 21, 18, 13 and 45, X respectively.- Following a positive NIPT result in the absence of a significant fetal structural anomaly (FSA), care is required in selecting the optimal diagnostic invasive test. Discussion of the limitations and implications is essential and referral to clinical genetics may be warranted.Learning objectives- To understand the embryological causes for and types of fetal placental mosaicism.- To appreciate underlying principles in NIPT and genomic testing strategies in relation to mosaicism.- To follow suggested clinical management principles in relation to prenatal test counselling.Ethical issues- Clinicians face a dilemma following a high-risk NIPT result in the setting of normal ultrasound. Awaiting long-term culture, as opposed to short-term culture on CVS, or amniocentesis delays potential termination of pregnancy.- Sex chromosome abnormalities on NIPT without an identifiable FSA cannot be interpreted reliably. Hence, NIPT should not be offered for sex chromosome aneuploidy.",

keywords = "exome sequencing, microarray, fetus, Mosaicism, NIPT, Fetal Diseases",

author = "Kelly Reilly and Samantha Doyle and Hamilton, {Susan J} and Kilby, {Mark D} and Fionnuala Mone",

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doi = "10.1111/tog.12850",

language = "English",

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T1 - Pitfalls of prenatal diagnosis associated with mosaicism

AU - Reilly, Kelly

AU - Doyle, Samantha

AU - Hamilton, Susan J

AU - Kilby, Mark D

AU - Mone, Fionnuala

PY - 2022/12/20

Y1 - 2022/12/20

N2 - Key content- Fetal placental mosaicism, of which confined placental mosaicism is a subtype, occurs in 2–3% of pregnancies.- Confined placental mosaicism may lead to a false positive result on non-invasive prenatal testing (NIPT) for common aneuploidies.- The risk of mosaicism in a chorionic villus sample (CVS) following a positive NIPT result is 2, 4, 22 and 59% for trisomy 21, 18, 13 and 45, X respectively.- Following a positive NIPT result in the absence of a significant fetal structural anomaly (FSA), care is required in selecting the optimal diagnostic invasive test. Discussion of the limitations and implications is essential and referral to clinical genetics may be warranted.Learning objectives- To understand the embryological causes for and types of fetal placental mosaicism.- To appreciate underlying principles in NIPT and genomic testing strategies in relation to mosaicism.- To follow suggested clinical management principles in relation to prenatal test counselling.Ethical issues- Clinicians face a dilemma following a high-risk NIPT result in the setting of normal ultrasound. Awaiting long-term culture, as opposed to short-term culture on CVS, or amniocentesis delays potential termination of pregnancy.- Sex chromosome abnormalities on NIPT without an identifiable FSA cannot be interpreted reliably. Hence, NIPT should not be offered for sex chromosome aneuploidy.

AB - Key content- Fetal placental mosaicism, of which confined placental mosaicism is a subtype, occurs in 2–3% of pregnancies.- Confined placental mosaicism may lead to a false positive result on non-invasive prenatal testing (NIPT) for common aneuploidies.- The risk of mosaicism in a chorionic villus sample (CVS) following a positive NIPT result is 2, 4, 22 and 59% for trisomy 21, 18, 13 and 45, X respectively.- Following a positive NIPT result in the absence of a significant fetal structural anomaly (FSA), care is required in selecting the optimal diagnostic invasive test. Discussion of the limitations and implications is essential and referral to clinical genetics may be warranted.Learning objectives- To understand the embryological causes for and types of fetal placental mosaicism.- To appreciate underlying principles in NIPT and genomic testing strategies in relation to mosaicism.- To follow suggested clinical management principles in relation to prenatal test counselling.Ethical issues- Clinicians face a dilemma following a high-risk NIPT result in the setting of normal ultrasound. Awaiting long-term culture, as opposed to short-term culture on CVS, or amniocentesis delays potential termination of pregnancy.- Sex chromosome abnormalities on NIPT without an identifiable FSA cannot be interpreted reliably. Hence, NIPT should not be offered for sex chromosome aneuploidy.

KW - exome sequencing

KW - microarray

KW - fetus

KW - Mosaicism

KW - NIPT

KW - Fetal Diseases

U2 - 10.1111/tog.12850

DO - 10.1111/tog.12850

M3 - Review article

SN - 1744-4667

JO - The Obstetrician and Gynaecologist

JF - The Obstetrician and Gynaecologist

ER -

Pitfalls of prenatal diagnosis associated with mosaicism

Abstract

Keywords

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