Biomedical subjects
Publications and source records attributed to U Froster-Iskenius.
The Caudal Dysplasia syndrome and the Femoral Hypoplasia-Unusual Facies syndrome have been reported to be more frequent among infants of diabetic mothers. We report a newborn girl who presented with features compatible with both syndromes. The possibility that both conditions represent different manifestations of the same disorder is discussed.
The article reports on a new method in prenatal diagnosis during the first three months of pregnancy. The gynaecological as well as the cytogenetic aspects are discussed on the basis of 74 transcervical trophoblast aspirations. Two different experimental preliminary examination series were conducted. In the first study, the failure rate in respect of recovery of material was 12.5%, whereas in the second examination series all aspirations were successful. Thanks to these favourable results, transcervical trophoblast aspiration was adopted as the only method used in prenatal diagnosis. In cytogenetic processing, direct chromosome preparation was found to be rather costly and time-consuming, whereas the short-term culture of chorionic villi usually yielded more favourable results in respect of mitotic rate and quality of the metaphase plates. It must be considered a drawback of transcervical trophoblast aspiration that it is not possible to conduct alpha-foetoprotein determination or determination of acetylcholine esterase as part of prenatal neural tube diagnosis. However, this can be subsequently done-with suitable disposition--during the 16th week of pregnancy, or can be replaced by a determination of alpha-foetoprotein in the serum of pregnant women.
The IQ levels of 18 female carriers with the marker X chromosome were evaluated, and cytogenetic studies after BrdU incorporation were performed. A highly significant correlation between mental capacity and replication pattern of the X chromosomes could be demonstrated. Heterozygous females with normal intelligence showed a clear tendency to carry the fragile site at the late replicating X chromosome, while other female carriers with lower intelligence or mental impairment expressed their fragile site mainly with the early replicating X chromosome. This observation could be interpreted as an expression of Lyonisation .
It is well established that apparently unaffected males can be transmitters of the marker X syndrome trait. Cytogenetic and clinical investigations of these male transmitters are only rarely reported for most of these male transmitters are dead by the time the syndrome is diagnosed in their families. We report on cytogenetic and clinical investigations of two unaffected male carriers of the disorder from two large families. Pedigree analysis of these families revealed six other cases of possible male transmission of the marker X syndrome trait. Mental impairment was not reported from the siblings of these unaffected male carriers and could not be observed in their daughters. The mode of transmission of the disorder cannot be fully explained by X-linked inheritance. The phenomenon of unaffected males transmitting the disorder could be due to an autosomal suppressor systeme. Our findings indicate that male transmission may be important for the frequency of the disorder.
Explore the source record for details and available documents.
Cytogenetic and morphological findings of a 20-gestational-week-old female fetus with karyotype 46,XX,i(18q) are reported. The fetus displayed clinical features resembling Edward's syndrome. No characteristic symptoms of monosomy 18p could be observed.
Among 242 institutionalized mentally retarded males in Northern Germany screened for fra(X)(q), 15 (6.2%) with severe mental retardation expressing fra(X)(q) were detected. One patient displayed Klinefelter's syndrome in addition. All fra(X)(q) males showed the typical facial signs, but three of the adults did not express macroorchidism. A preliminary estimation of an overall frequency of 1:2000 males for the fra(X)(q) condition is suggested.
Explore the source record for details and available documents.
Morbus Kniest was described by Springer and Wiedemann as an early form of dysplasia spondylo-epi-metaphysaria. The syndrome is combined with vitreoretinal degeneration. It is an autosomal dominantly inherited disorder, like Morbus Wagner. We report on a case with dwarfism and cataracta complicata. The diagnosis must be differentiated to Morbus Morquio.
Ten males with the fragile X (fra(X] syndrome were treated with folic acid (10 mg/day) for 4 months in a double-blind design study. To eight heterozygotes with mental impairment and fra(X), folic acid was given for 4 months (10 mg/day) in an effort to study possible beneficial effects of folic acid. Psychological and cytogenetic testing were carried out during the trial. There was no improvement in concentration, fine motor co-ordination, or comprehension in the adult male and female patients of the study. One patient showed improvement under a control medications. In the females, improvement was seen only in the youngest patient, a 5-year-old girl. Folate treatment does not seem to be effective in fra(X) adults, but may have some effect in children of both sexes with the disorder. Cytogenetic studies using peripheral lymphocytes showed that the fra(X) frequency decreased significantly (t = 0.00856; 1% level) only in cells cultured in a folic acid-free medium but not in cells cultured in a medium with added antifolate (methotrexate). This shows a "contamination effect" of folate-free culture medium after oral folic acid treatment of these patients. The decrease of fra(X) involves primarily the early-replicating X when culturing with folic acid-free medium. A synergistic suppression effect of "external folate" and BrdU is the most likely explanation of this phenomenon.
Evidence for the transmission of X-linked mental retardation through normal male carriers is reviewed in 6 kindreds. In these pedigrees we identified 15 unaffected males who likely had passed the gene on through their daughters. Fifty-one mentally retarded grandsons or great grandsons descended from these male carriers. In total, these males had 50 daughters with only 2 of them being of low intelligence. Two of the male carriers were recently identified through fra(X)- positive results in their mentally normal daughters. Among the sibs of these males, mentally retarded brothers were found in 3 families. This was unexpected since earlier observations suggested that the risk for mental retardation among sibs of nonmanifesting carriers is exceedingly low.
Female heterozygotes of the fra(X) form of mental retardation show variable degrees of mental impairment and phenotype expression of the disorder. This might be an effect of inactivation of the X-chromosome which carries the fra(X)(q). Prior replication studies in heterozygous carriers gave contradictory results with respect to possible genotype-phenotype correlation. In the interpretation of these studies it is important to understand the effect of BrdU on the fra(X)(q) expression. In a group of 13 hemizygous patients with fra(X)(q) and 7 heterozygous carriers we studied the effect of BrdU on fra(X) expression. In the heterozygous carriers the use of BrdU resulted in a significant suppression of the fra(X)(q), while in hemizygous patients no difference in fra(X)(q) frequency with or without BrdU could be observed. It can be concluded that BrdU suppresses the fra(X)(q) preferentially on the inactive X-chromosome. Thus the fra(X)(q) frequency on the active X-chromosome is of primary importance in phenotype correlation studies among heterozygous carriers. In our group of heterozygous carriers we observed a negative correlation between (IQ) phenotype and fra(X)(q) expression on the active X-chromosome. This suggests that the gene for the fra(X)(q) form of mental retardation is on the X-chromosome and undergoes inactivation.
Explore the source record for details and available documents.
We describe a family with two half-brothers affected with severe mental retardation. The phenotype in the affected individuals is characterized by apparent acromegaly, profound mental retardation, and hyperactivity. The mother has analogous but less severe facial anomalies and mild mental impairment. Screening for fra(X) (q) was negative in peripheral lymphocytes using methotrexate for fra(X) enhancement. The clinical findings in our patients are similar to those described by Fryns et al. [1986] in two patients with acquired lesions of the central nervous system. CT investigations in one of our patients showed areas of hyperdensity in the pontine region and a small subarachnoid cyst. The pedigree suggests X-linked inheritance. The association of apparent acromegaly, CNS anomalies, megalotestes, and mental retardation in this family supports the hypothesis that a distinct syndrome may exist with phenotype anomalies more severe than those characteristic for the Martin-Bell syndrome but without fragile X.
Longitudinal decline in IQ among fragile X males was reported recently. However, there are problems in retesting IQ that may affect scores. Two such factors are intertest time interval and score obtained on the first test. To determine the generality of IQ score changes, we examined 101 fragile X males from 6 centers. To ensure high test-retest reliability, only results from Stanford-Binet and Wechsler tests were used. Thus there were retest scores from 60 subjects. Test-retest reliability between first and last scores was very good (r = 0.85) and comparable to those seen in nonfragile X mentally retarded individuals. Also computed were z-scores of differences in IQ scores. The z-score differences were distributed about a mean at 1 SD below the expected zero value. Eighteen subjects showed statistically significant decreases in IQ, 6 showed statistically significant increases, while 5 showed the same scores. Z-score differences were not correlated with type of residence or elapsed intertest interval, but were negatively correlated with first score obtained, indicating a regression-to-the-mean effect. Using a multiple regression analysis, we found first score obtained, age tested, and age retested significant predictors of score differences, accounting for 19% of the total variance. These results suggest that factors previously identified as affecting retest scores have a smaller effect than originally thought. It is suspected that decline in IQ is associated with dynamic neurological processes and needs to be investigated further.
Fèvre-Languepin syndrome is a rare congenital malformation syndrome characterized in particular by the presence of a labio-maxillo-palatal cleft, anomalies of the reproductive organs and a bilateral popliteal pterygium. Findings in a boy who is now four years old are reported. As a result of 14 operations, as well as other therapy, a cosmetically and functionally satisfactory result has been achieved. The principal orthopedic surgical procedures and the postoperative management are described.