Autosomal dominant polycystic kidney disease: symptoms and clinical findings.

In 259 subjects at risk to have inherited autosomal dominant polycystic kidney disease (PKD), the frequency of symptoms consistent with urinary tract infection, haematuria, back and abdominal pain, hypertension, renal stones, and end-stage renal failure was evaluated. The diagnosis of PKD was made in 140 of these subjects (54 per cent). At the time of the study, 36 per cent of males and 7 per cent of females with PKD were asymptomatic, normotensive, and denied any previous problems. In patients younger than 30 years, 66 per cent of males but only 11 per cent of females were asymptomatic. In female patients, urinary tract infection (69 per cent) and hypertension (61 per cent) were the most frequent clinical manifestations. In contrast, in males with PKD, these problems were present in only 19 per cent and 42 per cent, respectively. Frequency of other clinical manifestations was similar in women and men with PKD. End-stage renal failure was present in 5 per cent of the 81 patients younger than age of 40, in 33 per cent of the 27 patients 40-49 years old, and in 47 per cent of the 32 patients aged 50 years or more. Physical examination was unreliable in estimating kidney size in most patients, particularly in early stages of the disease. Hypertension and symptoms such as haematuria and back pain, but not urinary tract infections, correlated well with renal size measured by radiograms.

Fertility and pregnancy complications in women with autosomal dominant polycystic kidney disease.

Fertility and pregnancy complications were assessed in 137 women at risk of having inherited the gene for autosomal dominant polycystic kidney disease. Seventy-six (55%) of these subjects were found to have polycystic kidney disease (multiple renal cysts). The remaining 61 women served as controls. The prevalence of fertility, spontaneous abortion, stillbirth, and symptoms consistent with urinary tract infection were not different in the two groups. However, the frequency of hypertension first diagnosed during pregnancy (with or without preeclampsia or eclampsia) and the frequency of pregnancy-unrelated hypertension were higher in women with polycystic kidney disease. No evidence was found that pregnancy had an adverse effect on the natural course of polycystic kidney disease. The incidence of renal failure was not higher in women with polycystic kidney disease who had three or more pregnancies than in women of similar ages who had two, one, or no pregnancies.

Clonal origin and trisomy of chromosome 15 in murine B-cell malignancies.

During the course of a multifaceted study of clonality in murine neoplasms we observed two B-lymphoid malignancies. Results of studies with the X-chromosome-linked enzyme phosphoglycerate kinase strongly suggest that these tumors had a clonal origin. Each of them had trisomy 15. This chromosomal abnormality has been found consistently in many murine thymic neoplasms, and has been thought to be specific to tumors of thymic origin. However, the occurrence of trisomy 15 in each of the only two B-cell malignancies thus far detected in our studies indicates that it may occur in B-lymphoid progenitors as well.

Autosomal dominant polycystic kidney disease: early diagnosis and data for genetic counselling.

Because of the onset of symptoms in patients with autosomal dominant polycystic kidney disease is generally delayed until adulthood, genetic counseling is imprecise. In an attempt to identify patients early, 261 offspring of subjects with the gene for polycystic disease were tested. Agreement between the results of excretory urography with nephrotomography and radionuclide imaging was excellent. In the 15-19 year age group, polycystic kidney disease was diagnosed in only 30% of 33 subjects at risk, whereas the expected figure was 50%. The disease was diagnosed in 57% of 228 subjects at risk who were aged over 19. When the probands were excluded, this figure was 43% and did not differ significantly from the expected 50%. These data suggest that persons at risk aged over 19 years who have normal urograms and radionuclide images have less than a 5% chance of having inherited the gene for polycystic kidney disease.

Liver cysts in patients with autosomal dominant polycystic kidney disease.

Liver cysts were found in 46 (29 per cent) of 158 patients over 10 years of age with documented autosomal dominant-type polycystic kidney disease (PKD) from 62 unrelated families. Hepatic cysts were not found in any patient at risk for PKD in whom renal cysts were not detected. The prevalence of liver cysts increased with advancing age and with declining rate of glomerular filtration. Results of clinical and laboratory studies indicate that polycystic liver disease in patients with autosomal dominant-type PKD is a benign condition, rarely, if ever, causing impaired liver function or portal hypertension.

Longitudinal studies of chromosomal abnormalities and reticulum cell proliferation in New Zealand Black mice.

A longitudinal study of 40 New Zealand Black (NZB) mice and 20 BALB/c control animals was performed. A significant association was observed between the presence of acquired spleen-cell aneuploidy at some time during life and development of histological evidence of reticulum-cell neoplasia in individual animals. This finding is compatible with the hypothesis that aneuploid clones which arise in the spleens of aging NZBs are at least potentially neoplastic. However, no relationship between histologically neoplastic reticulum cell proliferation and aneuploidy was apparent in single splenic specimens obtained from NZB mice of various ages. This lack of association indicates that failure to detect chromosomal abnormalities on direct study of cells from a tumor cannot be taken as evidence that the neoplastic cells themselves lack such abnormalities.

Specificity of acquired clonal chromosome abnormalities in New Zealand Black mice.

New Zealand Black (NZB) mice, an inbred strain characterized by immunological dysfunction and lymphoreticular malignancy, also develop populations of aneuploid spleen cells. In detailed cytogenetic analyses performed on 10 NZBs, the chromosomally abnormal cells were found to be clonally related within each mouse. Moreover, the karyotypic changes observed were highly non-random, usually involving the 15 (10/10 mice), 2 (8/10 mice), 16 or 17 (9/10 mice), and sex (6/10 mice) chromosomes. These observations suggest an important relationship between chromosomal alterations and tumorigenesis in NZB mice and emphasize the role of chromosome 15 in murine abnormal lymphoreticular proliferations.

The occurrence of gonadal dysgenesis in association with monozygotic twinning.

A case is presented of a monozygotic twin pair, discordant for phenotypic sex, in which the female member showed gonadal dysgenesis and chromosomal mosaicism. Review of the pertinent literature reveals that in monozygotic twin pairs, phenotypic and karyotypic concordance is the usual occurrence for Down's and Klinefelter's syndromes, whereas discordance often accompanies gonadal dysgenesis. Mosaicism is a frequent concomitant of gonadal dysgenesis in monozygotic twins. Our case strengthens the probability of a real association between mosaicism and monozygotic twinning in gonadal dysgenesis.