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Leigh syndrome

Other Names for this Disease
  • Leigh's disease
  • Leigh's necrotizing encephalopathy
  • LS
  • Necrotizing encephalopathy infantile subacute of Leigh
  • SNE
More Names
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Your Question

If a couple's first baby is diagnosed with Leigh syndrome, what is the chance that future children will have it as well? Is this condition inherited from the mother or father? 

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

How is Leigh syndrome inherited?

The inheritance pattern for Leigh syndrome varies depending on the specific mutation causing the disease in the individual. These mutations can be inherited as an autosomal recessive trait, an X-linked recessive trait, or as a mutation found within the mitochondrial DNA. In some cases of Leigh syndrome, no genetic cause can be identified.[1]

The autosomal recessive form of Leigh syndrome has been linked to mutations in one of several different genes. These genes cause specific enzyme deficiencies. All of these different genetic defects seem to have a common effect on the central nervous system, resulting in progressive neurological deterioration.[1] 

There is also evidence for an X-linked recessive form of Leigh's disease. This form has been linked to a specific genetic defect in a gene known as PDHA1 (E1-alpha subunit of the pyruvate dehydrogenase complex) that is located on the X chromosome.[1]

In some cases, Leigh syndrome may be inherited from the mother as a mutation found within the mitochondrial DNA (mtDNA). Mitochondria regulate the production of cellular energy and carry the genetic blueprints for this process within their own unique DNA. All human mtDNA comes from the mother. An affected mother will pass the traits to all of her children, but only the daughters will pass the mutation(s) onto the next generation. The specific mtDNA defect that may be responsible for some cases of Leigh syndrome is associated with a gene known as MT-ATP6. These cases are sometimes referred to as maternally inherited Leigh syndrome (MILS).[1]
Last updated: 10/6/2011

If a family has a child with Leigh syndrome, what is the risk of future children being affected? Is this condition inherited from the mother or father?

Leigh syndrome can be inherited as either an autosomal recessive trait, an X-linked recessive trait, or as a mutation found within the mitochondrial DNA.[1]

In autosomal recessive inheritance, a person inherits mutations in two genes, one from the father and one from the mother. If an individual receives one normal gene and one gene for the disease, the person will be a carrier and usually does not show symptoms. The risk for two carrier parents to both pass on the gene mutation and, therefore, have an affected child is 25% with each pregnancy. There is also a 50% risk in each pregnancy of having a child who is also a carrier; and a 25% of having a child that is neither affected nor a carrier.[1] 

In X-linked recessive disorders, a person can also inherit the condition from either parent. Females have two X chromosomes, but males have an X and a Y chromosome. In females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, they will show features of the disease if they inherit a gene mutation on the X chromosome. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50% risk of passing on the carrier condition to their daughters, and a 50% chance of transmitting the disease to their sons.[1] 

In some cases, Leigh syndrome may be inherited from the mother as a mutation found within the mitochondrial DNA (mtDNA). All human mtDNA comes from the mother. Thus, an affected mother will pass the traits to all of her children, but only the daughters will pass the mutation(s) onto the next generation.[1]

The genetic mutations that are present in the mtDNA may outnumber the normal copies of the genes. Symptoms may not occur until mutations are present in a significant percentage of the mitochondria. The uneven distribution of normal and mutant mtDNA in different tissues of the body can affect different organ systems in individuals from the same family and can result in a variety of symptoms in affected family members.[1]

A genetics professional can help determine how Leigh syndrome is being transmitted in a particular family.
Last updated: 10/6/2011

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 10/18/2013