Date of Award:

5-1-1971

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Department name when degree awarded

Zoology

Committee Chair(s)

Eldon J. Gardner

Committee

Eldon J. Gardner

Committee

J. R. Simmons

Committee

J. T. Bowman

Committee

R. Spendlove

Committee

C. Westby

Abstract

In 1951, Gardner (American Journal of Human Genetics, 3:167-176) reported that multiple polyposis followed a pattern of autosomal dominant inheritance in a Utah kindred, In 1952, Gardner and Plenk (American Journal of Human Genetics, 4:31-36) reported that all members of this family with polyposis also had multiple osteomas. In 1953, these same patients were found to have epidermoid cysts, fibromas, and ill-defined masses of connective tissue. In 1958, Smith (Diseases of the Colon & Rectum, 1: 323-332) suggested the term Gardner's syndrome to describe this spectrum of inherited pathological changes. Contact was re-established with this original kindred, and the pedigree updated. The kindred consisted of 165 family members covering six generations. Twenty-five family members were found to have inherited the syndrome. A number of genetic, clinical, and biochemical diagnostic studies were carried out on members of this kindred. Statistical analysis of this kindred plus 443 cases reported in the literature showed a slight excess of affected males over affected females. This excess was significant at the 5 percent level, but not at the one percent level. Estimations of the penetrance of the gene responsible for the syndrome were made using two different methods. The penetrance of the gene was calculated to be close to 100 percent. Clinical studies showed that three kindred members had developed classical desmoid tumors following surgery. It was concluded the occurrence of these rare fibrous tissue tumors is closely associated with the syndrome. However, they should not be considered an integral part of the syndrome as they may also occur in patients with simple familial multiple polyposis. On the other hand, dental anomalies were found to be an integral part of the syndrome. These abnormalities consisted of supernumerary, unerupted, and extremely soft and carious teeth. None of the affected members showed any abnormal pigmentation. The occurrence of scoliosis in two kindred members was considered coincidental, and studies to determine hypertelorism, brachymetacarpalism, and possible thyroid carcinoma were all negative. A study of the number of polyps fulgurated in the rectal stump ten to twenty years following surgery was studied in three cases. There was no significant reduction in the number of polyps which developed. In fact, the number of polyps actually seemed to increase with time. Upper gastro-intestinal x-ray surveys revealed no polyps in this area. Parathyroid hormone infusion studies indicated that patients with Gardner's syndrome are not refractive to the effects of the hormone as had been reported by Trygstad et al. (Journal of Clinical Endocrinology and Metabolism, 28:1153-1159) in 1968. Excretion of 3’ ,5'-Adenosine Monophosphate showed a normal response to the hormone indicating that the adenyl cyclase enzyme at the renal tubule site is normal. Hydroxyproline excretion was normal indicating a normal response to Parathyroid Hormone at the bone site. A modification of the Ellsworth-Howard test eliminated the classical sources of error and showed the expected normal increase in urinary phosphate clearance. Normal 24-hour excretion levels of hydroxyproline indicated there was not an unusually high rate of bone collagen turnover or degradation.

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