Dermatoglyphic analysis of fetuses with chromosomal abnormalities.

I applied Okajima's technique of exposing the dermal surface by chemical and mechanical treatment followed by toluidine blue stain to inspect the dermatoglyphic features of hands of aborted human fetuses with chromosomal abnormalities. The dermatoglyphic patterns of five fetuses, three with Down syndrome, one with 5p--, and one with 18 trisomy, were analyzed to determine whether the patterns were sufficiently specific to be used for diagnostic purposes. Apparently unique patterns were obtained. Observation of the dermal surface suggested that the developmental sequence of the ridges in fetuses with chromosomal disorders was retarded by more than 2 weeks as compared with that of normal fetuses of th same gestation.     

Ovarian dysgenesis in individuals with chromosomal abnormalities

Summary To understand better the pathogenesis of ovarian dysgenesis in individuals with abnormalities such as 45,X Turner syndrome, trisomy 13, and trisomy 18, we have examined microscopically the ovaries of 36 infants with a number of chromosomal abnormalities confirmed by karyotype analysis. All infants with trisomy 13, trisomy 18, triploidy, and 45,X were found to have severe ovarian dysgenesis characterized by a virtual absence of primary oocytes. The ovaries of individuals with 21 trisomy and of those with partial deletion or duplication of an autosome demonstrated variable findings, which ranged from complete absence of oocytes to a mild diminution of oocyte numbers. The results of this study suggest that the attrition of germ cells in these infants is a result of faulty meiotic pairing and that ovarian dysgenesis is a more frequent finding in children with karyotypic abnormalities than has been realized previously.Presented, in part, at the 1989 David W. Smith Morphogenesis and Malformations Conference, Madrid, 1989, and at the 1990 Southern Society for Pediatric Research Meeting, New Orleans, 1990     

Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities

The most common type of karyotype abnormality detected in infertile subjects is represented by Klinefelter's syndrome, and the most frequent non-chromosomal alteration is represented by Y chromosome long arm microdeletions. Here we report our experience and a review of the literature on sperm sex chromosome aneuploidies in these two conditions. Non mosaic 47,XXY Klinefelter patients (12 subjects) show a significantly lower percentage of normal Y-bearing sperm and slightly higher percentage of normal X-bearing sperm. Consistent with the hypothesis that 47,XXY germ cells may undergo and complete meiosis, aneuploidy rate for XX- and XY-disomies is also increased with respect to controls, whereas the percentage of YY-disomies is normal. Aneuploidy rates in men with mosaic 47,XXY/46,XY (11 subjects) are lower than those observed in men with non-mosaic Klinefelter's syndrome, and only the frequency of XY-disomic sperm is significantly higher with respect to controls. Although the great majority of children born by intracytoplasmic sperm injection from Klinefelter subjects are chromosomally normal, the risk of producing offspring with chromosome aneuploidies is significant. Men with Y chromosome microdeletions (14 subjects) showed a reduction of normal Y-bearing sperm, and an increase in nullisomic and XY-disomic sperm, suggesting an instability of the deleted Y chromosome causing its loss in germ cells, and meiotic alterations leading to XY non-disjunction. Intracytoplasmic injection of sperm from Y-deleted men will therefore transmit the deletion to male children, and therefore the spermatogenic impairment, but raises also concerns of generating 45,X and 47,XXY embryos.     

Neonatal outcome of fetuses with urinary tract abnormalities diagnosed by prenatal ultrasonography.

Between 1979 and 1986 an abnormality of the urinary tract was diagnosed by prenatal ultrasound examination in 93 fetuses. Postnatal investigation at a large teaching hospital showed a definite abnormality in 85 infants, 66 of whom were boys. An obstructed urinary tract, usually requiring surgery, was present in 46 infants. Other abnormalities included a multicystic kidney (in 15 infants), vesicoureteric reflux (in 9), prune-belly syndrome (in 5) and polycystic kidneys (in 5). Early recognition and treatment of urinary tract disorders in infants should be accompanied by informed prenatal counselling to minimize parents'' anxiety.     

Similar chromosomal abnormalities in several retinoblastomas

Summary The study of banded chromosomes of nine sporadic unilateral retinoblastomas revealed near diploid karyotypes with multiple numerical and (or) structural abnormalities in all tumors. An identical marker i(6p) was noted in cells of the modal class of six retinoblastomas. Extra copies of the short arm of chromosome 6 were observed in seven tumors: +i(6p) in 6 and +6q- in one. Less regular but repeated findings were a loss of one sex chromosome, and markers 1p+ and 17q+. The structure of these markers was not identical in different tumors. Abnormalities of chromosome 13 were not observed in tumor cells, nor in blood lymphocytes stimulated by PHA.     

10p- Syndrome associated with multiple chromosomal abnormalities

Summary A karyotype with six de novo autosomal abnormalities in chromosomes 2, 4, 9, 10, 12, and 13 was identified in a 7-year-old boy with mental retardation and other minor malformations. The G-and C-banding techniques revealed an equilibrated translocation between autosomes 2 and 4 and between autosomes 9 and 13. One chromosome 10 has lost genetic material from its short arms, probably because of an interstitial deletion. An unidentified chromosomal fragment has become inserted in the long arms of an autosome 12. The G bands demonstrate that genetic material inserted in the autosome 12 is not the genetic material deleted from the autosome 10.The propositus presents clinical features similar to the reported cases with 10p-syndrome. Nevertheless it is not possible to establish the influence of the genetic material inserted in autosome 12 on the propositus' phenotype.     

Unexpected chromosomal abnormalities in prenatal diagnosis. 4 case reports with preservation of the pregnancy

Four unexpected karyotypes were found in prenatal diagnosis: 47,XXX; 47,XXY; double reciprocal translocation; Yq-. Supplementary biological studies (including specific Y-DNA probes) are carried out in order to help in the parents' decision. No induced abortion was performed. The children are described after delivery.     

Analysis and visualization of chromosomal abnormalities in SNP data with SNPscan

Background  

A variety of diseases are caused by chromosomal abnormalities such as aneuploidies (having an abnormal number of chromosomes), microdeletions, microduplications, and uniparental disomy. High density single nucleotide polymorphism (SNP) microarrays provide information on chromosomal copy number changes, as well as genotype (heterozygosity and homozygosity). SNP array studies generate multiple types of data for each SNP site, some with more than 100,000 SNPs represented on each array. The identification of different classes of anomalies within SNP data has been challenging.     

Risk of chromosomal abnormalities, with emphasis on live-born offspring of young mothers.

In a large public urban hospital obstetrics service with > 123,000 deliveries in a 10-year period (1980-89), the frequencies (0.12%) of any type of chromosomal abnormality and of trisomy syndromes were analyzed for maternal age-related risk, by logistic regression. Focusing on very young gravidas, we found that in the study period there were 9,332 births (7.5% of all deliveries) to mothers < or = 16 years old. Estimated risks of chromosomal abnormalities among offspring associated with very young maternal age (9-16 years) were similar to those age-associated risks of mothers 20-29 years old. Risks of chromosomal abnormalities increase with advancing maternal age and are independent of ethnicity.     

Age-related nonrandom chromosomal abnormalities in human low-grade astrocytomas

We report a cytogenetic investigation of 55 low-grade astrocytomas in 52 patients, 15 children and 37 adults. In addition to numerical aberrations such as trisomy 7 and gonosomal losses, we found structural and/or numerical aberrations of chromosome 1 in eight astrocytomas. There was a striking difference between the rearranged chromosomes in pediatric and adult patients. Whereas the pediatric tumors revealed monosomies 1p with accompanying trisomy 1q, the astrocytomas in adults showed partial or complete monosomies 1q.     

Maternal age and chromosomal abnormalities in human oocytes

Maternal ageing is the only etiological factor unequivocally associated with the occurrence of aneuploid conceptuses. Molecular studies of trisomies have demonstrated that the pattern of recombinaison was an important predisposing factor to meiotic nondisjunction. To complete this data, a large chromosomal study has been undertaken on 1,397 unfertilised human oocytes recovered from women participating in in vitro fertilization programmes. Conventional whole chromosome nondisjunction and premature chromatid separation were the major types of numerical abnormalities observed. A positive relationship was found between maternal age and these two types of nondisjunction, but the most significant correlation was observed with chromatid separation resulting in the presence of free chromatid in metaphase II oocyte. These data revealed that chromatid separation was an essential factor in the age-dependent occurrence of aneuploidy. This finding provided new insights into the mechanism of nondisjunction in female meiosis since disturbance in molecular chromatid cohesion by cohesins might be a causal mechanism predisposing to nondisjunction and involved in the maternal age effect.     

Somatic chromosomal abnormalities in infertile men and women

Infertility--the inability to achieve conception or sustain a pregnancy through to live birth--is very common and affects about 15% of couples. While chromosomal or genetic abnormalities associated with azoospermia, severe oligozoospermia or primary ovarian failure were of no importance for reproduction prior to the era of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), advances in assisted reproductive techniques (ART) now enable many infertile couples to have children. These developments have raised the question of the genetic consequences of ICSI: concerns of the potential harm of the invasive procedure and concerns about the genetic risk. The infertile male and female definitely have an increased risk to carry a chromosomal abnormality. Detection of such an abnormality is of fundamental importance for the diagnosis of infertility, the following treatment, the evaluation of the risk for the future child and the appropriate management of the pregnancy to be obtained. Therefore, cytogenetic screening of both partners is mandatory prior to any type of ART. The present review is based on several surveys on male and female infertility and analyzes the types and frequencies of the different reported chromosome abnormalities according to the type of impairment of spermatogenesis and the type of treatment planned or performed. With regard to assisted reproductive techniques (especially ICSI) the main types of chromosomal abnormalities are discussed and their potential risks for ICSI. If available, reported cases of performed ICSI and its outcome are presented. The detection of an abnormal karyotype should lead to comprehensive genetic counselling, which should include all well-known information about the individual type of anomaly, its clinical relevance, its possible inheritance, the genetic risk of unbalanced offspring, and the possibilities of prenatal diagnosis. Only this proceeding allows at-risk couples to make an informed decision regarding whether or not to proceed with ART. These decisions can be made only when both partners have clearly understood the genetic risks and possible consequences when ART is used.     

Thyroid function after bronchography with propyliodone

Thyroid function was studied in 27 subjects who underwent bronchography with propyliodone (18-70 ml, containing 30% of organic iodine). Sustained elevations of serum non-hormonal iodine were observed, indicating that significant amounts of propyliodone were absorbed from the bronchial tree and also that elimination may take several weeks. During the period of anaesthesia, there was an increase in thyroxine-binding globulin and all thyroid hormones which was transient and probably reflected vascular response to the anaesthetic. T4-T3 conversion was inhibited with a nadir of T3 and a peak of rT3 occurring on the 2nd day after propyliodone exposure. FT4 increased gradually during the 2 weeks after bronchography, but remained within the normal range. 6 out of the 27 patients developed pathologic T4 levels, 3 elevated T3 levels, and 2 an abnormal response to thyrotropin-releasing hormone; these changes might have been confused with hyperthyroidism. None of the patients developed clinical thyrotoxicosis; however, in patients with autonomous thyroid tissue, the same precautions should be taken with propyliodone as with other iodine-containing agents which are known to induce hyperthyroidism in this situation.     

Thyroid function in pregnancy

Iodine is required for the production of thyroid hormones. Normal thyroid function during pregnancy is important for both the mother and developing fetus. This review discusses the changes in thyroid physiology that occur during pregnancy, the significance of thyroid function tests and thyroid antibody titers assessed during pregnancy, and the potential obstetric complications associated with maternal hypothyroidism.