Chromosome Studies in Neonates of the Prešov Region (Slovakia)

Overview

The aim of the study was retrospective analysis of chromosome aberrations in neonates born during 1998–2007 in the Prešov region (Eastern Slovakia). Karyotyping was done in 247 children suspected of having chromosomal abnormalities out of 26 693 live born infants. The abnormal karyotype was detected in 17.4% of the cases. Chromosome abnormalities were recorded and compared with other studies.

Results confirm the significant contribution of chromosomal abnormalities in the genesis of congenital malformations. A chromosomal study of each child with congenital malformation is recommended in all the pediatric sections of the hospitals for the proper managment of such cases.

Key words:
chromosome aberrations, neonates, congenital malformations, cytogenetics

Introduction

Chromosome aberrations form a major part of the genetic load carries in the human population. The frequency of various chromosomal abnormalities is quite different in neonates (0.7%) as compared with abortuses (about 50%), some aneuploidies are lethal in utero [1]. The impact of chromosomal abnormalities is greatest during fetal life when they have their highest frequency and form a major cause of fetal loss [2].

The occurence of autosomal aberrations in live born infants was ascertained to 1:400 of cases. The occurence of gonosomal aberrations in live born boys was ascertained to 1:400, in girls 1:650 [3]. Newborn with congenital malformations exhibite chromosomal abnormalities in 24.1% of the sases [4]. With development of chromosome analyses methods the scale of known chromosome aberrations is extended.

The prevention of chromosomally caused congenital malformations is the major indication of prenatal diagnostics. At the present time, prenatal genetic diagnostics and prevention of chromosome aberrations are indicated by the mother´s age, positive biochemical screening of the maternal serum and ultrasound examination. The accurate and reliable cytogenetic examination decides about futher strategy in prenatal care of genetic risk pregnancy.

Patients and methods

We analyzed the occurence of chromosome aberrations in 247 liveborn infants with suspected chromosome aberration born in 1998–2007 in the Perinatological Centre of the Faculty Hospital of J. A. Reiman Prešov. All neonates with suspected chromosomal aberration were subjected to a full genetic study; complete genetic examination and pedigree construction was done for exclusion nonchromosomal causes of anomaly.

Cytogenetic examinations were performed from lymphocytes of peripheral blood using standard methods [5]. Lymphocytes of peripheral blood were cultivated 72 hours in RPMI medium with 10% fetal calf serum at 37°C. The cell divisions were arrested in the metaphases by adding colchicine 4x10⁵ M for 30–40 minutes before harvesting the culture. Cultures were treated with 0,4% potassium chloride hypotonie solution and fixed in 3:1 methanol-acetic acid mixtures. Metaphase chromosomes were analyzed by conventional color methods, G-banding and C-banding cytogenetic analysis for structural and numerical chromosome abnormalities. At least 30 banded metaphases were analyzed in each case. Cytogenetic analyses were performed on Wright’s G-banded chromosomes according to ISCN nomenclature [6].

Results

Between 1998 and 2007, 247 infants with suspected chromosome aberration were refered for cytogenetic examination out of 26 693 neonates in the Prešov region. The number of newborn infants which were born in separate years is presented in Figure 1.

Cytogenetic examinations revealed chromosomal abnormalities in 43 neonates (17.4%). 40 (16.2%) involved autosomes, while only 3 (1.2%) involved gonosomes.

13.3% (32/247) of newborns had autosomal trisomy. Among those, 96.9% had free trisomy 21, 3.1% had translocation trisomy 21. In analyzed survey trisomie 18 was not noted.

One newborn (0.4%) had trisomy 13 and one had trisomy 22. Two newborns (0.8%) had partial autosomal aneuploidy, one infant with a partial monosomy of chromosome 18 was detected (karyotype 46,XY,del(18)(p11)), one had karyotype 46,XY,del(4)(p16)). In one newborn inversion of chromosome 12 was observed (karyotype 46,XY,inv(12)(q22)). One newborn had unbalanced derivative chromosome in mosaic form resulting from t(3;10) translocation. In one newborn supernumerary marker chromosome was detected, also. The exact nature of the marker chromosome could not be identified. In one case a chromosome constitution with two cell lines: karyotype 46,XX/46,XX,t(7;14)(q32;q13) was diagnosed. Three patients (1.26%) had sex chromosome abnormalities (karyotype 45,X). Some data of newborns with a chromosome abnormalities are summarized in Table 1.

Considering the total population of live born infants surveyed, the incidence of chromosomal abnormalities was 1.61/1000, the incidence of structural chromosomal abnormalities was 0.19/1000 and that of numerical abnormalities 1.42/1000. The frequencies of these abnormalities are compared with other studies in Table 2.

Discussion

Several cytogenetic surveys of consecutive births were undertaken to establish the incidence of aneuploidy and structural chromosomal rearrangements in human population. A considerable variation in the frequency of chromosomal abnormalities is observed in these studies. There are wide variations in the frequency of chromosomal aberrations in individuals suspected of having genetic disorder as reported by different investigators [7, 8, 9].

The occurence of chromosome aberrations refered by authors are influenced by various factors, hence they are a rather disparate. Several studies have shown documented chromosomal abnormalities among unselected populations of neonates and older children. The frequency of chromosomal abnormalities is known to be significantly higher in selected populations than in unselected populations.

In consecutive neonatal studies, autosomal abnormalities are usually as common as sex chromosome aberrations [10]. In studies based on a reffered population with suspected chromosome aberration, such is the present work, autosomal abnormalities are much higher than those of the gonosome. This figure is in agreement with other surveys [5, 16].

In literature 0.7% the frequency of chromosome aberrations in live born infants was noted [11]. Ferák and Sršeň (1990) noted 0.5–1.0% occurence of chromosome aberrations in live born infants [12]. In the present work chromosomal aberrations were detected in lower per cent than in most of the previously mentioned studies [13].

In previously studies the frequency of chromosome aberrations in the Prešov region (Eastern Slovakia) were mapped. From the overall number of 4748 cytogenetic analyses (1990–2005) 1.3% of Down syndrome cases were detected [14]. It is a similar frequency as noted Hsu (1992) [15].

Although individually rare, partial autosomal aneuploidies are second the most common chromosomal abnormality after trisomy 21 [2]. The frequency found in our study was lower than that repoted by other authors [13, 16].

The incidence of Turner syndrome in consecutive neonates has been reported to be 0.004% [13]. In our study it was 0.011%. In previously study in the Prešov region 1.16% of cases with cytogenetic diagnosis of Turner syndrome were detected [17]. Comparision of incidences indicate that there was a considerable reduction in the occurence of this type of chromosome aberration. The reasons may be various including factors of handhold individuals with suspected chromosome aberration. Conventional analyses allow diagnostics of Turner syndrome individuals, which is necessary for following therapeutic advancements for these patients.

In the present study one newborn had trisomy 22 as the result of balanced translocation t(11;22)(q25;q12) detected in his father. Boroňová et al. (2008) detected three families with constitutional translocation t(11;22) with family occurence in balanced and nonbalanced form [18]. In probands and individual members of families variable fenotypical picture with different degree of mental retardation was detected. Cytogenetic examination of neonates with multiply development anomalies disclose their causal reason.

Most of pericentric inversions observed in humans do not give rise to any specific phenotypic abnormalities. However, pericentric inversion has been found to be associated with infertility, repeated fetal loss, congenital anomalies and mental retardation [10, 19, 20]. Pericentric inversion has been implicated as a possible predisposing factor for nondisjunction and interchromosomal effect [21].

The occurence of each type of chromosome abnormality in this study was lower that obtained results from previous studies [4]. Distinct methodological approaches to analysis induce that results often cannot be compared to each other. The differences in percent of detected chromosome aberrations may be explained by many various factors, e.g. the various size of study survey, various access of selected individuals, extension of prenatal diagnostics and various approaches of cytogenetic examination.

Prenatal genetic diagnostic is a part of prenatal care. Prenatal karyotyping is used to identify major genetic and congenital abnormalities in a developing fetus. Abnormal karyotypes in the Prešov region (Eastern Slovakia) in 2000–2004 were prenatally diagnosed with frequencies ranging from 2.1% to 7.3% [22]. Identification of fetal abnormal chromosomes in high risk pregnancies allows proper pediatric and obstetric managment of the cases as well as genetic counselling. The choice and utilization of optimal genetic methods allow improvement the strategy of medical care about genetic risk pregnancy.

Conclusion

Many congenital malformations have a genetic cause, chromosomal studies should be undertaken in every child with congenital abnormalities. The present study amproves that chromosomal study is useful in investigation of every child with congenital malformation of unknown origin for confirmation of clinical diagnosis, it allows proper genetic counselling and managment of such cases. The most chromosome abnormalities associated with congenital malformations can be detected soon after birth on the basis of cooperation between pediatricians and genetics. Diagnostic of genetic disorders and counselling parents of newborns with possible genetic condictions takes up a significant proportion of a neonatologist´s clinical time.

Anna Sinaiová, MD
Perinatological Centre
Faculty Hospital of J. A. Reiman
Hollého 14
080 01 Prešov
Slovak Republic
e-mail: sinaiova@fnsppresov.sk