HEMOPHILIA 415 



can no longer be strictly maintained on account of many exceptions to this 

 rule. _ Grandidier has described the predisposition, transmissibility, and the 

 hereditary seq^uence in hemophilia in the following paragraphs : 



_ 1. Men from families of bleeders who are bleeders themselves, whose 

 wives are^ not^ descended from bleeder families, by no means always beget 

 hemopMic children; on the contrary, in these cases the children are frequently 

 healthy with no tendency to the disease. Vice versa, however, it appears that 

 hemophilia quite invariably appears among the children of women who are 

 bleeders. 



2. Men descended from bleeder families without being bleeders themselves, 

 and whose wives are from normal families, rarely beget hemophilic children; 

 on the other hand, women belonging to bleeder families who are not themselves 

 bleeders, give birth almost invariably to children who suffer conspicuously from 

 hemophilia. 



On account of the gravity of hemophilia, its continuity in families, and 

 the fatal outcome which is usually due to severe hemorrhage, also because of 

 popular interest and the mysterious character of the affection, it is natural 

 that records regarding bleeder families extend far back into the past. 



Grandidier, in his well-known monograph, cites 200 bleeder families with 

 609 male and 48 female bleeders (^13 to 1). In the bleeder family de- 

 scribed by Stahel there were 24 males, all bleeders, in four generations. Al- 

 though females are much more rarely attacked by the disease than males, yet 

 transmission most certainly occurs through the female members of the family. 

 In Bollinger's collection of cases it appears to be the rule, as in color-blindness 

 (Daltonism), that the sons of women whose fathers were bleeders are most 

 liable to hemophilia. 



Otto and Nasse have published reports regarding the first recorded bleeder 

 families. Among those that have become especially well known are the fam- 

 ilies at Tenna in Graubiindten, the American family, Appleton-Browe, and the 

 Mampel family at Kirchheim near Heidelberg, whose genealogical tree was 

 first described by Chelius in the year 1827, then by Mutzenbecher in 1841, 

 and lately by Lessen (Fig. 22). This ancestral tree shows that the tendency 

 to bleed is transmitted exclusively through the female members of the family 

 who themselves without exception remained unaffected, a peculiarity which 

 we shall later discuss in another affection, hereditary Daltonism. Vice versa, 

 from marriages between male bleeders and female aon-bleeders healthy chil- 

 dren are born. 



Worthy of note also is the proportion between boys and girls in the vari- 

 ous generations : In the first generation from the common ancestors, there 

 are four boys and two girls; three of these boys (or 75 per cent.) are bleeders, 

 but none of the girls. In the second generation there are 14 boys and 9 girls ; 

 of the former 13 (or 93 per cent.) are bleeders, of the latter, none. Finally, 

 in the third generation, among at least 50 children, there is only one bleeder, 

 a male who was the offspring of a non-bleeder mother belonging to the same 

 ascending line. There is, therefore, a conspicuous diminution of the disease 

 in the third generation, and this is probably due to intermarriage with healthy 

 families. 



