Family planning for Leigh syndrome, like other mitochondrial diseases, can be complex because the condition may be inherited in different ways. Some assisted reproductive technologies (ART) and testing options are only available for certain inheritance patterns. This page is intended to help families better understand the available options and considerations.
In memory, Millie, USA
Assistive Reproductive Technologies
Available reproductive options for Leigh syndrome and other mitochondrial diseases differ depending on whether the condition is caused by nuclear DNA or mitochondrial DNA variants. Nuclear DNA variants are typically inherited similarly to many other genetic conditions and have several well-established reproductive testing options. In contrast, mitochondrial DNA inheritance is more complex and often requires consultation with a specialized mitochondrial disease or reproductive genetics center.
We also recognize that navigating these decisions can be emotionally difficult and overwhelming. Please explore the additional resources listed at the bottom of this page or contact us if you need additional support.
Prenatal Diagnosis (PND)
Prenatal diagnostic testing may be considered when a pregnancy is already underway. Chorionic villus sampling (CVS), typically performed between 11–13 weeks of pregnancy, analyzes placental cells, while amniocentesis, usually done between 15–17 weeks, analyzes fetal cells present in the amniotic fluid.
PND can detect known nuclear DNA variants in a pregnancy and is a well-established clinical option that may help inform pregnancy decisions and medical planning.
PND can also detect mitochondrial DNA variants. However, testing for mitochondrial DNA conditions is more complex because the relationship between the percentage of affected mitochondria (heteroplasmy) and disease severity is not fully understood for all variants. In addition, PND for mitochondrial DNA variants is only offered in limited specialized settings.
Preimplantation Genetic Testing (PGT)
Preimplantation genetic testing is an in-vitro fertilization (IVF) technique in which eggs and sperm are collected from prospective parents, the eggs are fertilized in the lab to create embryos, and then the embryos are screened for genetic variants prior to transfer to the uterus.
PGT is widely used for nuclear DNA variants associated with a variety of genetic conditions and is a well-established option routinely offered in clinical practice.
PGT for mitochondrial DNA variants has also shown promising results in research studies and may be available through some specialized mitochondrial disease clinics; however, it is still considered a research-based option focused on risk reduction rather than complete risk elimination.
Mitochondrial Replacement Therapy (MRT)
Mitochondrial Replacement Therapy (MRT), also called Mitochondrial Donation (MD) may be an option for women who carry mitochondrial disease-causing variants. MRT is a form of in-vitro fertilization in which a woman’s eggs are collected and their affected mitochondria is replaced with healthy mitochondria from a donor.
MRT is not currently available in the United States, although promising research and early clinical experience have been published in the United Kingdom. At this time, MRT is considered a risk reduction approach rather than a complete risk-elimination technique.
MRT is only relevant for women with mitochondrial DNA mutations.
Current Research on PGT and MRT for Mitochondrial DNA Inheritance
Quincy and Jack, USA
Recent research published in the New England Journal of Medicine (NEJM) reported encouraging early outcomes from studies performed in the United Kingdom using preimplantation genetic testing (PGT) and mitochondrial donation/replacement therapy (MRT/MD) for mitochondrial DNA disease.
- The papers reported 22 children born following PGT and 8 children born following mitochondrial donation in the United Kingdom.
- Most infants were born with undetectable or low levels of affected mitochondrial DNA.
- While these results are promising, experts emphasize that these approaches are currently considered risk-reduction rather than risk-elimination strategies.
- Additional research and long-term follow-up are still needed.
Papers:
For additional research papers related to reproductive options and mitochondrial disease, please visit “Genetics and Reproductive Strategies” section of our Papers page.
Other Family Planning Options
Available reproductive options for Leigh syndrome and other mitochondrial diseases differ depending on whether the condition is caused by nuclear DNA or mitochondrial DNA variants. Nuclear DNA variants are typically inherited similarly to many other genetic conditions and have several well-established reproductive testing options. In contrast, mitochondrial DNA inheritance is more complex and often requires consultation with a specialized mitochondrial disease or reproductive genetics center.
We also recognize that navigating these decisions can be emotionally difficult and overwhelming. Please reach out to us if you would like support or help finding resources.
Sperm Donation
Men with mitochondrial DNA variants cannot pass them on to their children. However, men with nuclear DNA variants can and may choose to use a sperm donor to avoid this.
Egg Donation
Women with either nuclear or mitochondrial DNA variants may choose to use an egg donor. Utilization of an egg donor allows affected women to carry their child but the nuclear DNA that contributes to the child will consist of the father and the egg donor.
Adoption
Adoption remains a family planning option for all individuals, whether affected with nuclear or mitochondrial DNA variants.
Information and Support Resources
Media Library – Courageous Parents Network (not mito specific)
Listening, Reflecting, Healing (supportive genetic counseling)
Family Planning and Financial Considerations (by Global Genes)
Podcast episodes (Part 1 and Part 2) from the Johns Hopkins Berman Institute of Bioethics featuring a family’s journey after losing a child to mitochondrial disease and their experience using preimplantation genetic testing (PGT) to have two subsequent children.
If you have more resources we can list here please be in touch with us!
Frequently Asked Questions About Family Planning and Reproductive Options for Leigh Syndrome and Mitochondrial Disease
What reproductive options are available for families affected by Leigh syndrome or other mitochondrial diseases?
Families affected by Leigh syndrome or other mitochondrial diseases may consider several reproductive options, including natural conception, preimplantation genetic testing (PGT) with IVF, prenatal diagnosis (CVS or amniocentesis), donor egg or donor sperm, adoption, and mitochondrial replacement therapy (MRT), also called mitochondrial donation (MD), in countries where it is available. The options available depend on the genetic cause of Leigh syndrome and individual family circumstances.
Can preimplantation genetic testing (PGT) prevent Leigh syndrome or mitochondrial disease?
For Leigh syndrome or mitochondrial disease caused by a nuclear DNA variant, PGT is a well-established reproductive option that can identify embryos that do not carry the disease-causing variant before pregnancy. While no medical test can guarantee a specific outcome, PGT for nuclear DNA disorders is highly accurate and is routinely used in clinical practice.
For Leigh syndrome or mitochondrial disease caused by a mitochondrial DNA variant, PGT may help reduce the risk of transmission in some cases. However, because mitochondrial DNA inheritance is more complex and disease severity may not correlate perfectly with the proportion of affected mitochondria, PGT for mitochondrial DNA disorders is generally considered a risk-reduction strategy rather than a risk-elimination strategy.
What is prenatal diagnosis?
Prenatal diagnosis refers to testing during pregnancy to determine whether a fetus has inherited a known genetic variant. Common methods include chorionic villus sampling (CVS), usually performed between 11 and 13 weeks of pregnancy, and amniocentesis, usually performed between 15 and 17 weeks.
For Leigh syndrome caused by a nuclear DNA variant, prenatal testing can usually determine whether the fetus has inherited the disease-causing variant. For Leigh syndrome caused by a mitochondrial DNA variant, interpretation may be more complex because the proportion of affected mitochondria (heteroplasmy level) may vary and may not always predict disease severity. Families should discuss the benefits and limitations of prenatal testing with a genetics professional.
Is genetic testing necessary before considering reproductive options?
Yes. Identifying the genetic cause of Leigh syndrome is often the first step in understanding which reproductive options may be available. Different options may be appropriate depending on whether the condition is caused by a mitochondrial DNA variant or a nuclear DNA variant.
What is mitochondrial replacement therapy (MRT) or mitochondrial donation (MD)?
Mitochondrial replacement therapy (MRT), also called mitochondrial donation (MD), is a reproductive technique designed to reduce the risk of passing on certain mitochondrial DNA variants. The procedure combines nuclear DNA from the intended parents with healthy donor mitochondria from an egg donor.
MRT/MD is relevant only for women with disease-causing mitochondrial DNA variants. It is currently not available in the United States and remains an area of ongoing research and clinical development. While early results are promising, MRT/MD is considered a risk-reduction approach rather than a guarantee that mitochondrial disease will not be passed on.
Can people with mitochondrial DNA variants use IVF and PGT?
In some situations, women with mitochondrial DNA variants may be candidates for IVF with PGT. Because mitochondrial DNA inheritance is complex and levels of affected mitochondria can vary, consultation with a specialized mitochondrial disease center is recommended.
Should families affected by Leigh syndrome meet with a genetic counselor?
Yes. A genetic counselor can help explain inheritance patterns, discuss recurrence risks, review testing options, and help families understand which reproductive options may be appropriate for their situation.
Can someone who has a child affected by Leigh syndrome also have healthy children?
Yes. Many families who have one child affected by Leigh syndrome go on to have healthy children. The likelihood of having another affected child depends on the specific genetic cause of Leigh syndrome, the inheritance pattern, and the reproductive approach chosen.
Because Leigh syndrome can result from variants in either nuclear DNA or mitochondrial DNA, recurrence risks vary widely between families. A genetic counselor or mitochondrial disease specialist can help explain the risks and discuss reproductive options that may help reduce the chance of passing on the condition.
What is the difference between mitochondrial DNA and nuclear DNA inheritance?
Nuclear DNA is inherited from both parents, while mitochondrial DNA is inherited almost exclusively from the mother. Because Leigh syndrome can result from variants in either mitochondrial DNA or nuclear DNA, understanding the genetic cause is important when discussing family planning options.
Where can families learn more about reproductive options for Leigh syndrome or other mitochondrial diseases?
Families should discuss reproductive options with a genetic counselor, reproductive endocrinologist, maternal-fetal medicine specialist, and/or mitochondrial disease specialist. Cure Mito Foundation also provides educational resources and links to additional information on family planning and reproductive options.
