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One hundred and seventy-six individuals with various colorectal diseases were investigated simultaneously for increased in vitro tetraploidy in dermal fibroblast cultures and for occult mandibular osteomas. In only 10 of the 176 persons were both presumed markers of colorectal genetic predisposition present in the same individual. No evidence was found that these traits are causally associated. A combination of the two presumed markers showed a tendency towards occurrence in individuals with a positive family history of colorectal cancer among first-degree relatives.

Orthopantomography of the mandible was carried out on 50 patients with colorectal cancer without known familial disposition. Twelve patients (24%) had osteomas, as against 5% in the control group (P less than 0.001). Since an increased occurrence of mandibular osteomas has earlier been demonstrated in cases of familial polyposis coli and the family cancer syndrome, we must conclude that genetic factors are presumably of more importance in the development of colorectal cancer than previously assumed.

In all affected members of a family with Gardner's syndrome the complete triad of skin tumours, osteomas and polyps of the colon has developed since 1968 when examination revealed an apparently bisymptomatic variant of Gardner's syndrome. In this family bony changes consisting of circumscript osteomas, diffuse sclerosing zones within certain bones, and ridge-like widening of the corticalis were noted, having developed during puberty but remaining constant thereafter. Similarly, no significant new skin tumours appeared after puberty. Most colonic polyps however, occurred in adolescence or thereafter, with malignant transformation after a variable interval of several years. The necessity of long-term observation of the colon, also in patients presenting with a bi- or monosymptomatic form, is stressed. Coloscopy has proven to be more useful diagnostically than radiological methods.

Orthopantomography of the mandible (OTM) showed osteomas in 3 of 34 non-affected sibs and children of the probands in 14 families with polyposis coli. The observed to expected ratio with osteomas was 0.35, which is not significantly lower than 1.0 and in accordance with the frequency in the normal population. Although the result does not enable a definite evaluation of the diagnostic value of OTM, the finding suggests that this method may be used as a supplement to regular proctosigmoidoscopic screening of first-degree relatives of polyposis patients.

A case of a woman with Gardner's syndrome, originally manifested by multiple adenomatous polyps of the colon, is presented. She underwent subtotal colectomy at 14 years of age. Over the next 15 years she had a composite odontoma, an impacted supernumerary tooth, two epidermal inclusion cysts, multicentric paillary-follicular adenocarcinoma of the thyroid, two tubulovillous adenomas of the duodenum in which argyrophilic cells were a prominent feature, and an adenomyoma of the gastric antrum. The presence of all of these lesions in one patient expands the spectrum of lesions seen with Gardner's syndrome and supports the concept of a generalized abnormality of growth regulation as the cause of the syndrome.

Two cases of Gardner's syndrome in one family are presented. The father presented all three stigmas of the syndrome, while in the daughter no osseous manifestations were found. In the first patient, the diagnosis was made only after the second abdominal operation, when a mesenteric fibrous mass was seen. In the second case, the intestinal polyposis was clinically suspected, considering the hereditary aspects of this syndrome, and the episode of bloody diarrhea presented by this patient. Both patients were treated by subtotal colectomy with ileo-rectal anastomosis. Both of them presented fibrous tumors after the abdominal operation (the father after six years and the daughter after one year). The authors stress the importance of postoperative followup for the detection of fibrous masses that may appear due to the surgical stimulus. The literature on Gardner's syndrome is reviewed and summarized.

Abdominal masses, "desmoid tumors," occur in approximately 4% of patients with Gardner's Syndrome, usually 1--3 years after total colectomy. Histologic sections usually resemble those of an infiltrating fibrous tumour, a desmoid lesion. The radiographic pattern may be similar to any diffuse abdominal retroperitoneal tumor, metastatic disease, lymphoma, or possibly retractile mesenteritis. The clinical setting usually differentiates these entities.

Hereditary osteodystrophy of Albright's is a set of hereditary dystrophies associated or not with renal and bony resistance to the parathyroid hormone. Two observations of a true brotherhood are reported. These two patients had in common: short stature, obesity (especially facio-troncular), round face, flat and saddled nose, short neck, early cataract and mental deficiency. One of them showed fourth metacarpals. In these two cases there were cutaneous ossifications, markedly profuse on one of them than the other. These ossifications are a frequent manifestation of the osteodystrophy of Albright's. They appear as cutaneous nodules on any part of the body and are visible, palpable and present on X-ray examination. These ossifications share other phenotypic expressions of the disease and do not seem to be related to the resistance against parathyroid hormone.

Tetraploidy was increased in skin fibroblast cultures grown in the laboratory at the same time under the same conditions and derived from 2 probands with the Gardner syndrome and 9 affected members of one family as compared to that occurring in cultures from 5 relatives by marriage and 10 normals. Tetraploidy was present at the first subculture (2 weeks after the initial biopsy was cultured), and for each line studied the percentage of dividing cells showing tetraploidy remained constant. The relation of the observed tetraploidy to the increased risk of such patients to develop abnormal growths and cancer has not been established. The increased tetraploidy should be of value in identifying the presence of the gene for the Gardner syndrome in high risk families.

Multiple familial ossifying fibroma is a very rare jaw lesion. A 31-year-old white woman who had this heritable condition is reported. A differential diagnosis has been discussed to delineate an entity that has not appeared in the previous literature.

The cases are presented of two siblings with multiple cutaneous tumours associated with adenomatous polyps of the colon and bony abnormalities. In one patient an adenocarcinoma of the colon supervened, and there was a history of adenocarcinoma of the colon without the presence of other abnormalities in a third sibling. Clinically the sebaceous tumours resembled sebaceous hyperplasia, but histologically they exhibited features of sebaceous adenoma.The association of a variety of multiple soft tissue tumours, particularly epidermal cysts, with polyposis of the colon and bony abnormalities is well recognized. However, multiple solid sebaceous tumours have not been reported previously as a feature of this syndrome. They should in future alert the physician to the possible presence of multiple polyposis of the colon in affected individuals and immediate relatives.

The Gardner syndrome is an autosomal dominant condition characterized by multiple polyposis of the colon, associated with various soft- and hard-tissue tumors. Our original kindred, first reported in the early 1950's has been updated and serves as the basis for a discussion of the penetrance and expressivity of the gene responsible for the syndrome. The family consists of 188 members spread over six generations, with 28 individuals clearly documented as having the syndrome. Using two different methods of calculating penetrance, the responsible gene was found to be fully penetrant. This observation was confirmed by an analysis of 160 additional sibships from the literature. This estimation of penetrance is considerably higher than has been previously reported. The expressivity of the gene, however, is quite variable, and this is illustrated using examples from both our kindred and the literature.

Carcinoma of the colon is commonly seen in the Gardner syndrome and familial polyposis of the colon. Therefore early detection of these symdromes in families and careful follow-up are important. During a study of families at high risk of developing colorectal cancer, an asymptomatic 19-year-old female was found to have the Gardner syndrome. Although barium enema examination was negative, colonoscopy revealed the presence of polyps; biopsy of one polyp revealed carcinoma-in-situ.

Human hereditary tumors in vivo are known to show tissue specificity. Increased endoreduplication with tetraploidy has been shown to occur in cultures established only from tissue containing epithelium (skin and colonic polyps) from patients with the Gardner syndrome. Cultures established from blood (short-term lymphocyte and lymphoid suspension) and connective tissue (subcutaneous tissue, lipoma, mesentery, and sebaceous cyst) from the same patients did not show increased tetraploidy. These observations demonstrated that tetraploidy as an expression of the gene for the Gardner syndrome was cell-specific in vitro and added further evidence that increased tetraploidy could be used for detection of the Gardner gene in families at risk.

The molecular structure of murine retroviruses expressed in spontaneous and radiation-induced bone tumours was studied. These viruses induce osteomas, lymphomas and osteopetrosis in mice of the NMRI strain. RNase T1 fingerprint analysis indicates the presence of mixed virus populations in the tumours, with major components showing close relationship to Akv MuLV. Cloned viruses, closely related to Akv MuLV, have the same oncogenic properties as the original mixtures. In its nucleotide sequence of the repeat segments of the transcriptional enhancer in the LTR, one cloned virus analysed was distinct from Akv MuLV, but closely related to a spontaneous bone tumour virus isolate, FBJ MuLV.

Many pathologists, gastroenterologists, and oncologists agree that villous (papillary) adenomas of the large bowel are at risk for the development of large bowel cancer. The role of adenomatous polyps (tubular adenomas) in the genesis of large bowel cancer is not a point of agreement. Future studies with molecular biologic techniques of colon polyps and adjacent mucosa and of the colonic mucosa of animals under treatment with colon carcinogens may clarify the role of colon polyps and other factors in the genesis of large bowel cancer. Polyps larger than 1.0 cm should be removed thrugh the proctosigmoidscope or the colonoscope.

Patients from two families are reported who exhibited features of Gardner's syndrome: familial polyposis coli; epidermoid cysts; and osteomata. The difficulty in defining this syndrome, its clinical features and suggested management are discussed. Follow up has been difficult in one family because of the late age at which lesions developed, and because family members have moved interstate. The premalignant potential of Gardner's syndrome is emphasized.

Adenomas and hamartomas, two genetically transmitted histologic types of gastrointestinal polyposis, are associated in syndromes with extragastrointestinal manifestations. Adenomas that predispose to adenocarcinoma are basic to familial polyposis coli, the Gardner syndrome and the Turcot syndrome. Gastrointestinal polyps and extragastrointestinal lesions serve as a warning, providing time for diagnosis and treatment of adenomas to prevent their malignant transformation in patients and their relatives. Hamartomas with no malignancy potential, but having a tendency toward bleeding and bowel obstruction, are associated with the Peutz-Jeghers syndrome, juvenile polyposis, multiple hamartoma syndrome, basal-cell nevus syndrome and the Cronkhite-Canada syndrome. Most of these lesions and syndromes follow the inheritance pattern of a single autosomal dominant gene.

The clinical manifestations of Gardner's syndrome were studied in 280 patients from 11 families. Forty-five per cent of the patients at risk inherited the syndrome. Forty-one patients had carcinoma of the intestine develop, with only a 27 per cent survival rate for this type cancer. Eight per cent of the patients with the syndrome showed peritoneal fibrosis and fibrous tumors. They also had carcinomas of the ampulla of Vater, liver, bldder and ovary develop as well as osteogenic sarcoma. The patients without the syndrome had carcinomas of the pancreas and breast develop as well as melanoma and leukemia. Twelve of the 16 patients having had a colectomy and ileoproctostomy showed regression of the remaining polyps of the rectum.

Dental and bone abnormalities of the maxilla and mandible are present in approximately 80% of patients with familial polyposis coli. The dental abnormalities include impacted teeth (other than third molars), supernumerary teeth, congenitally missing teeth, fused roots of first and second molars, and unusually long and tapered roots of posterior teeth. The bone lesions consist mostly of osteomas, either isolated or in clusters, in the maxilla and mandible or of exostoses with lateral and/or lingual extensions. Since dental and bone abnormalities are already present early in life there is a strong suggestion that they may be used as diagnostic features in the recognition of familial polyposis coli.

A family with Gardner's syndrome including one autopsy case is reported. A 22 year-old man had multiple polyposis of the colon and the small intestine, epidermal cysts, soft part tumor of the abdominal skin and osteomas in the calvarium and rib, and died of a carcinoma in the transverse colon and embolism of the brain. Histologically, all polyps were diagnosed as adenomatous polyp. The greater their diameter, the higher the tendency of atypism was observed. However, the polyps around the cancer were few, small, and with low atypism, and we could not obtain evidence showing direct transformation of adenomatous polyps into carcinoma. His two elder brothers had multiple polyposis of the colon, epidermal cysts and osteomas in the calvarium or mandibular bone, but are still alive.

Familial aggregations of tumors may occur in virtually all organ systems. The gastrointestinal tract is a frequent site for the development of cancers having an hereditary basis. Their recognition has important relevance to cancer control and prevention. In addition, detailed clinical and laboratory studies of inherited tumors may throw light upon the cause of the more common forms of gastrointestinal neoplasms. Radiologists must have a working knowledge of the genetic and diagnostic elements of each in order to fulfill their responsibilities to the patient, the patient's family and the referring physician.

Orthopantomograms of the mandible were performed on 46 patients with familial polyposis coli having no clinical signs of Gardner's syndrome and on 46 control patients matched according to age and sex. Thirty-five patients (76.1 per cent) and two (4.3 per cent) controls had osteomas (P less than 0.0005). It is concluded that orthopantomography of the mandible is a valuable diagnostic supplement to prophylactic proctosigmoidoscopic examination of first-degree relatives of polyposis patients. Due to the frequent occurrence of mandibular osteomas in polyposis patients without clinically detectable extracolonic manifestations, it is suggested that "Gardner's syndrome" is no longer considered a clinical entity.

We have examined 15 members of a family with Gardner's syndrome. In the first and second generations, 4 (possibly 5) of 6 members died of cancer of the colon/rectum. Two of them were known to have plyposis coli. Three members of the third generation had the complete triad of Gardner's syndrome with polyposis coli, soft tissue and hard tissue tumours. Three of 5 children in the fourth generation, aged between 7 and 11 years, probably have polyposis coli, and 2 of them have stigmata of Gardner's syndrome. All members of any family with Gardner's syndrome should be examined regularly at 2--3 year intervals from an age of about 10 years until the diagnosis is established, or if polyposis does not develop, up to the age of 40 years. Proctocolectomy is recommended at the age of 18--20 years or later as soon as the diagnosis is determined.

A family of 68 members in six generations has been investigated, and thus far 23 of these have had colorectal polyposis, cancer, or both. Many of the 23 have had a variety of soft tissue lesions, occult osteomas of the mandible, and dental abnormalities. Six of nine siblings in the proband's immediate family had diffuse colorectal polyposis and soft tissue lesions, as have 4 of their 20 children. One of three members of the most recent generation has polyposis and skin lesions. Retrospectively, 2 of the proband's 18 maternal cousins had colorectal polyposis or cancer, as did five of six siblings in her mother's generation. Four of nine siblings in the previous generation died from colon cancer, and so did their father. In the first three generations cancer was prevented in only 1 of 10 patients. Two of 13 in the later three generations thus far have died from colorectal cancer. Both coloproctectomy and colectomy with preservation of the rectum have been utilized in the patients in this study. Lifelong follow up is underway for those whose rectum has been removed.

This report describes a family with familial polyposis and lymphoid polyps in which a single member exhibits features of Gardner's Syndrome. A review of the literature pertaining to the simultaneous occurrence of lymphoid polyposis with Gardner's Syndrome and familial polyposis is presented. The importance of histologic diagnosis is stressed.

One hundred and seven patients (57 patients with ulcerative colitis and 50 controls) were investigated for in vitro tetraploidy (IVT) in dermal fibroblast monolayer cultures. There was no difference in incidence of IVT between patients with ulcerative colitis and controls. We advance the hypothesis that the genetic background of the colorectal cancer type found in ulcerative colitis differs from that found in the colon cancer syndromes and in non-hereditary colorectal cancers. Colorectal cancer in ulcerative colitis is probably only dependent on the degree of inflammatory lesions of the colonic mucosa.

The role of heredity in the production of gastrointestinal tumours is reviewed. The rare forms showing Mendelian inheritance are described, with special reference to oesophageal cancer and to familial polyposis of the colon. The high risks in these disorders are contrasted with the generally low risks to family members for the common cancers of the digestive tract. The part played by genetic factors in production of the premalignant state is critically discussed, with emphasis on gastric and hepatic cancer. The various experimental genetic approaches to the causation and early detection of cancer are outlined, and it is concluded that both genetic and environmental factors should be considered together when the etiology is being investigated.