The authors begin with a historical review of the first genetic investigations concerning familial amyloidotic polyneuropathy in the North of Portugal by C. Andrade. Then they review the studies made by other authors about this curious hereditary disease. A dominant mode of transmission was found in all investigations and the area of Povoa de Varzim could be confirmed as the focus where the mutation took place for the first time. Later on the affection spread throughout the northern part of Portugal before finally migrating also to the American continent. The early inquiries of Andrade in 1951-52 were concerned with a still fairly limited number of cases (74 cases). A systematic genetic and statistical study became, however, necessary for the whole material collected over almost 30 years by C. Andrade et al. The individuals examined now amount to 623, 249 of whom are affected (153 males and 96 females, distributed over 148 sibships). After applying various methods of correction (maximum-likelihood-method and Weinberg's method) and while making a distinction between simple selection (k=0) and complete selection (k=1), the authors come to the following evaluations: for K=0, the average of individuals affected (corrected) per sibship is of 21.26±1.88% (method of maximum likelihood scores); for k=1, this value is of 30.84±2.26%. When considering separately within the sibships the male and female patients, the following figures are obtained: for k=0, respectively 13.06±1.33% for males and 8.20±0,98% for females; for k=1, 18,95±1.68% for males and 11.89±1.29% for females. The percentages obtained with Weinberg's method are more or less the same (21.26±1.75% and 31.39±2.50% for k=0 and k=1, respectively). Since the material was collected during a systematic survey of all families affected, the figures computed for k=1 (complete selection) must be considered correct (30.8% by the maximum-likelihood-method and 31.4% by Weinberg's method). In respect of the sex ratio in the families studied, a predilection for the male sex was revealed when all families with at least one member affected are taken into account. However, when considering the families with at least two members affected, the sex ratio corresponds to 1:1. As to morbidity risk, our values are clearly below those of Becker (1964): whereas the figures found by Becker range between 0.32 and 0.50, ours lie between 0.26 and 0.31. The discrepancy must be attributed to the fact that our material which was numerically more important than Becker's provided for a more equitable evaluation of the sex ratio and excluded the possibility of a sex controlled gene. According to our investigations, there is therefore no difference between the sexes as to the degree of penetrance of the affection. The discordance between the sexes is practically restricted to the age of manifestation of the disease, 33 years on an average for males and 44 years for females. The assumption must consequently be made that this one difference is sufficient to guarantee transmission of amyloidotic polyneuropathy through the generations, in spite of counterselection that operates to the detriment of the responsible gene. © 1969 Springer-Verlag.
