Two pairs of proven monozygotic twins discordant for familial amyloid neuropathy (FAP) TTR Met 30

Twin studies are an important tool in medical genetics for the evaluation o f the relative roles of genetic and non-genetic factors in several diseases . Familial amy-Ioidotic polyneuropathy type I (FAP-I), TTR Met 30, was pres ent in two sets of proven monozygotic (MZ) twins, one from Majorca and the other from Portugal. Monozygosity was established by analysis of DNA polymo rphisms. Both pairs were discordant for age at onset and some clinical mani festations of FAP-I. We reviewed the differences in age at onset and clinic al features in both sets and in two other pairs of presumed MZ twins with F AP-I and compared them with those in MZ twin pairs with other Mendelian dis orders, such as neurofibromatosis type 1, Huntington's disease, facioscapul ohumeral muscular dystrophy, and myotonic dystrophy. We conclude that, in a ddition to the postulated modifying genes, there must be a significant cont ribution from non-genetic factors to the phenotypic variability of FAP-I (a ge at onset and clinical expression), either because of enviromental differ ences or stochastic events during(or after) the twinning process.