Variable expressivity

The severity of many autosomal dominant conditions varies
considerably between different affected individuals within the
same family, a phenomenon referred to as variable expressivity.
In some disorders this variability is due to instability of the
underlying mutation, as in the disorders caused by
trinucleotide repeat mutations (discussed in chapter 7). In
many cases, the variability is unexplained. The likely severity in
any affected individual is difficult to predict. A mildly affected
parent may have a severely affected child, as illustrated by
tuberous sclerosis, in which a parent with only skin
manifestations of the disorder may have an affected child with
infantile spasms and severe mental retardation. Tuberous
sclerosis also demonstrates pleiotropy, resulting in a variety of
apparently unrelated phenotypic features, such as skin
hypopigmentation, multiple hamartomas and learning
disability. Each of these pleiotropic effects can demonstrate
variable expressivity and penetrance in a given family.