Abstract

The birth ranks and parental ages at birth of subjects affected with Huntington's disease were ascertained from the literature and examined in relation to the neurological sign displayed (muscular rigidity or choreo-athetosis). With respect to the sex of the affected parent, the percentage of rigid cases was found to decrease linearly with advancing paternal age and to increase linearly with advancing maternal age. In contrast, no significant relation was found for birth rank or for age of the unaffected parent.

The results could be explained in terms of the somatic gene-mutation theory of Burch by invoking a `switching mechanism' which converts a predisposing autosomal allele for rigidity in the germ cell of affected fathers into one which is expressed as chorea. The converse mechanism is postulated to occur in affected mothers. Calculation showed that the hypothetical mutation rates were of the same magnitude in affected parents of each sex.