Autosomal Dominant Inheritance, Reduced Penetrance - Example

Pedigree

The autosomal dominant condition is usually represented in each generation, but with reduced penetrance, a generation may appear to be "skipped" because of the lack of phenotypic expression. In the above pedigree, a male in the 2nd generation displays reduced penetrance.

Huntington Disease

Huntington disease occurs from a mutation in the huntingtin gene encoding for a protein in the central nervous system. The presence of the abnormal protein causes a movement disorder. Since the onset of the disease occurs in middle age (40's), it is easy to pass the condition on to children without knowing it. This phenomenon of apparent lack of phenotypic expression for a time is called delayed onset. The specific abnormality is what is known as a "triple repeat" in which there are increased numbers of a particularly sequence of DNA (tandem repeats). In this case, there are multiple CAG repeats. Unaffected persons have 11 to 35 copies, while affected persons have 36 to 100 copies. Incomplete penetrance is seen at 36 to 38 copies. In general, the number of repeats increases with successive generations, leading to worse symptoms and earlier appearance.

This disease exhibits the phenomenon of penetrance, and not all persons with the genetic disorder (genotype) express manifestations of the disease (phenotype). Such persons are said to have reduced penetrance of the disease. This confounds family history taking, since the carrier may be missed.