Section 15 — Human Generics 



is a familial disease with autosomal dominant 

 inheritance. 



The tumors in adenomatosis and in some other 

 inherited deseases always grow in multiple 

 fashion in the affected organs. In view of the 

 great regularity of this finding the presence of 

 multiple tumors in one organ and/or of symme- 

 trical tumors in paired organs can be used as a 

 priori evidence of their genetic origin. It is 

 assumed that tumor-multiplicity comes about 

 by necessity: it presumably results from the 

 action of a growth-promoting gene endowed 

 with pleiotropism of cell-reaction (Hadorn). The 

 insulomas in the Zollinger-Ellison syndrome are 

 not inherited and are therefore solitary like other 

 not genetically determined tumors. Their micro- 

 scopic picture likewise sets them apart from the 

 inherited tumors of adenomatosis, which is true 

 of solitary isletcell tumors in general. 



From the genetic point of view the Zollinger- 

 Ellison syndrome appears as a partial pheno- 

 copy of the inherited syndrome of adenomatosis 

 of endocrine glands. 



15.45. Hereditary Hyperparathyroidism. 



E. Jackson (Bluffton, U.S.A.). 



Charles 



The purpose of this paper is to present four 

 families with hyperparathyroidism seen at our 

 institution in the past six years — the first with 

 9 members affected in two generations, the 

 second with a father and son affected, the third 

 with a woman and her great nephew affected and 

 a fourth with 5 members affected in two gener- 

 ations. These pedigrees and those in the literature 

 suggest an autosomal dominant type of in- 

 heritance. 



The finding of other endocrine adenomata in 

 members of 2 of these families has emphasized 

 that hereditary hyperparathyroidism is most 

 likely a part of the syndrome termed hereditary 

 endocrine adenomatosis. 



The ascertainment of several asymptomatic 

 cases in these family studies led to the speculation 

 that hyperparathyroidism might be more com- 

 mon than had been realized in the past. To test 

 this possibility, routine serum calcium deter- 

 minations were performed on 12,000 consecutive 

 patients coming to our general medical clinic 

 with the finding of 10 cases of hyperparathy- 

 roidism (an incidence of almost 1 in 1000). This 

 again illustrates how genetic studies help provide 

 data on the true incidence of certain diseases. 



During this 6-year period only 10 other index 

 cases have had parathyroid adenomas removed 

 at our institution. Since only 11 other families 

 have been reported in the literature, the finding 



of these 4 families in our small series suggests 

 that heredity is a more important factor in the 

 etiology of parathyroid adenomas than has been 

 recognized previously. 



15.46. Albright's Hereditary Poly-osteo-chondro- 

 dysplasia ( Pseudo-pseudohypoparathyroidism). 

 Luc Goeminne (Ghent, Belgium). 



In 1942 Albright described a syndrome with 

 biological and clinical findings characteristic of 

 hypoparathyroidism but refractory to parathy- 

 roid extract. The syndrome was labelled pseudo- 

 hypoparathyroidism (PHP) because the target- 

 organ (renal tubule) fails to respond adequately 

 to parathyroid hormone. 



The patients show a typical morphologic 

 syndrome, various dyschondroplastic anomalies, 

 tissue-calcifications ossifications, exostoses and 

 trophic disturbancies (teeth, eye-lens, skin) 

 (67 cases reported in 1960, first familial cases 

 published in 1950). 



In 1952 Albright described a syndrome without 

 symptoms or biological findings of tetany, but 

 with the same somatic features, named pseudo- 

 pseudohypoparathyroidism (PPHP) (50 cases 

 known in 1962, first familial cases reported in 

 1957). 



Symptoms are: short size, obesity, round 

 face, brachydactyly. 

 We describe a family with 



1. 1 case of PPHP, diabetes, hypertension, 

 polyarthritis, arteritis (femoral artery 

 ectopie calcifications). 



2. 1 case of PPHP with hypertension. 



3. 1 case of PPHP with polyarthritis. 



4. At least 4 other cases of PPHP and 2 PPHP 

 "formes frustes". 



This is the second observation in Belgium after 

 the 3 cases described by Nagant and Hoet, in 

 1960. 



Our pedigree is the first in the medical litera- 

 ture where more than 5 cases of PPHP are found 

 in 4 successive generations. 



The association of PPHP with diabetes 

 (25 per cent), hypertension (25 per cent), 

 hypothyroidism (15 per cent), polyarthritis 

 (15 per cent) and gonadal dysgenesis (25 per cent) 

 is probably significant. 



Hypertension and diabetes might arise from 

 diffuse calcifications and clerosis of renal and 

 pancreatic arteries (?). 



McKusick, Uhr and Bezahler (1961), Mann 

 (1962) and Schwartz (1963) suppose a sex-linked 

 incomplete dominance. Our extensive pedigree 

 suggests, (yet with one exception of a clear male- 

 to-male transmission), this mode of inheritance 



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