What Do Geneticists Mean by Anticipation?

Anticipation describes how certain genetic disorders become more severe and appear at an earlier age as they are passed from one generation to the next.

Overview

The signs and symptoms of some genetic conditions tend to become more severe and appear earlier as the disorder is transmitted across generations. This phenomenon is called anticipation. It is most often observed in nervous system disorders such as Huntington's disease, myotonic dystrophy, and fragile X syndrome.

Mechanism: Trinucleotide Repeat Expansion

Anticipation typically occurs with disorders caused by a specific type of mutation known as a trinucleotide repeat expansion. A trinucleotide repeat is a sequence of three DNA nucleotides that is repeated consecutively. When the number of repeats becomes abnormal, the DNA segment becomes unstable and prone to errors during cell division. As the gene is passed from parent to child, the repeat count can increase—a process termed expansion. In some cases, the expansion grows large enough to disrupt normal gene function, leading to more severe disease features in each successive generation.

Clinical Variability

Most genetic disorders exhibit variability in signs and symptoms among affected individuals, even within the same family. Not all of this variability is explained by anticipation. A combination of genetic, environmental, and lifestyle factors likely contributes, although many of these factors remain unidentified. Researchers examine multiple generations of affected family members and consider the underlying genetic cause before concluding that a disorder demonstrates anticipation.

Further Reading

For additional information about anticipation:

• The Merck Manual Professional Version provides a brief explanation of anticipation.
• The Myotonic Dystrophy Foundation describes anticipation in the context of myotonic dystrophy.

Related Topics in the “Inheriting Genetic Conditions” Chapter

• What does it mean if a disorder seems to run in my family?
• Why is it important to know my family health history?
• What are the different ways a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• What are reduced penetrance and variable expressivity?
• What do geneticists mean by anticipation?
• What are genomic imprinting and uniparental disomy?
• Are chromosomal disorders inherited?
• Why are some genetic conditions more common in particular ethnic groups?
• What is heritability?

Other chapters in Help Me Understand Genetics