Estimation of the age at onset of Huntington's disease from factors associated with the affected parent

Abstract

In an attempt to relate the age at onset of Huntington's disease to parental factors, the effects of parental onset age [P(o)] and the age of the transmitting parent at the birth of a subsequently affected child [P(c)] have been examined in a sample of cases ascertained from Victorian kindreds. There was a significant positive linear regression of onset age on the variable P(o)-P(c); the result was independent of the sex of affected parent or child. It is suggested that the pathogenetic process is activated in individuals at a fixed time before their genetically determined onset ages and need not commence at birth. Somatic gene mutations accumulating with age may interact with modifiers activated at initiation of pathogenesis and favor the transmission of genes determining early onset. An important conclusion for genetic counselling is the desirability of parents at risk who intend to have children to plan their families early in life so that the illness will tend to appear in late adulthood in their affected children. The regression equation may also be applied to estimate the risk of inheritance of the disorder and, by taking interfamilial variation into account, appears to have an advantage over the existing method based on the distribution of onsettages.