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POLG-Related Disorders

  • What is POLG-Related Disorders?

    POLG-related disorders consist of multiple inherited disorders with broad and overlapping symptoms affecting many tissues and organs, especially brain, nerves, muscle, and liver. These disorders are caused by the deficiency of DNA polymerase gamma, the enzyme required for mitochondrial DNA synthesis. Ages of onset range from early childhood to adulthood and many individuals have some, but not all, of the symptoms of one or more of the individual disorders. Alpers syndrome, the most severe and prevalent form in the spectrum of POLG-related disorders, is characterized by seizures, loss of mental and movement abilities, and liver disease. People with Alpers syndrome usually begin symptoms before age four years and survive for 3 months to 12 years after onset of the first symptoms. Autosomal dominant progressive external ophthalmoplegia (PEO) is an adult-onset POLG-related disorder, which causes the eyelids to droop. Symptoms and severity are not predictable based on the pathogenic variants present in a person. There is no cure for POLG-related disorders but medical surveillance and care may help to improve some symptoms and overall condition of life. Some medicines for epilepsy treatment may make liver disease much worse and should be avoided. POLG-related disorders are caused by pathogenic variants in the POLG gene.

  • How is POLG-Related Disorders inherited?

    POLG-related disorders are generally inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers. The exception is autosomal dominant PEO (adPEO) which is inherited in an autosomal dominant manner. This type of inheritance requires the presence of one copy of a pathogenic variant in the gene, inherited from one parent, for the child to have the genetic disease. There is a 50% chance that a baby will inherit one mutant copy of the gene and be affected when one of the parents carries a pathogenic variant.

  • What does it mean to be a carrier?

    There are generally no signs or symptoms associated with being a carrier for POLG-related disorders that are inherited in an autosomal recessive manner. However, the risk to have a child affected with POLG-related disorders is increased. Testing of reproductive partners is recommended for carriers of POLG-related disorders.

  • How common is POLG-Related Disorders?

  • What is analysed?

AFFECTED SYSTEMS
Brain
Eye
Liver
Hearing
Gitract
CARRIER RATES
Ethnicity Detection Rate Carrier Frequency
General Population > 95% 1 in 50