anticipation
Anticipation is a pattern in which an inherited disease shows up earlier in life, or hits harder, in each successive generation of a family. A grandparent might develop mild symptoms in old age, a parent earlier in adulthood, and a child in their teens. It can look almost as if the illness is gathering momentum as it passes down the family tree.
For most disorders that show genuine anticipation, the underlying cause is an unstable trinucleotide repeat expansion that tends to grow longer when transmitted from parent to child. A longer repeat usually means earlier onset and more severe disease, so as the repeat lengthens across generations, the symptoms march earlier. Huntington disease, myotonic dystrophy and fragile X syndrome are classic examples.
Historically, apparent anticipation was sometimes an illusion caused by how families were studied, for example noticing severe early cases first, or simply paying closer attention to later generations. Geneticists are careful to confirm that a true molecular mechanism, the lengthening repeat, is at work before accepting anticipation as real.
In one family, a grandmother developed myotonic dystrophy symptoms in her sixties, her son in his thirties, and her grandchild showed signs from birth, mirroring a repeat that lengthened with each transmission.
Earlier onset down the generations is the visible face of a growing repeat.
In some disorders the degree of anticipation depends on which parent transmits the gene; for example, severe early-onset Huntington disease is more often inherited from an affected father.