Prenatal detection of complex chromosomal aberrations using advanced molecular cytogenetic techniques.

OBJECTIVE: This study aimed to identify a marker chromosome and characterize the short arm of a derivative chromosome 5 in a foetus with the following karyotype: mos 47,XX,del(5)(p?),+i(5)(p10)[50]/48,XX,del(5)(p?),+i(5)(p10),+mar[25]. METHOD: Amniocentesis was performed in the 26th week of pregnancy because of ultrasound abnormalities (polyhydramnion and decreased amount of gastric filling). All classic banding techniques were performed. FISH and microdissection combined with reverse painting were used to reveal the exact origin of the marker and any extra material on the deleted chromosome 5p. The parents decided to continue the pregnancy and we compared the clinical features of the child born in week 34 with data from the literature on trisomy 5p. The possible contribution of trisomy of the centromeric region of chromosome 8 and trisomy 8p23.3-->8pter to this clinical picture was evaluated. RESULTS: GTG banding showed one normal and two aberrant chromosomes 5 [del(5)(p?) and i(5)(p10)] in all the cells examined. Furthermore, a supernumerary marker chromosome was present in approximately 30% of the cells. The marker was CBG positive and positive with the pancentromere probe, but dystamicinA/DAPI negative. It did not contain NOR-positive satellites. FISH proved this marker to be derived from the centromeric region of chromosome 8. MicroFISH disclosed the aberrant chromosome 5 as der(5)t(5;8)(p10;p23.3). The parent's karyotypes were normal. The baby showed the characteristic features of trisomy 5p syndrome. She died at the age of 15 days after cardiorespiratory arrest. CONCLUSION: The karyotype was interpreted as mos 47,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10) (WCP5+,D5S23+)[50]/48,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10)(WCP5+,D5S23+),+mar.ish 8(p10q10)(D8Z2+,WCP8-)[25]. Therefore, the baby had complete trisomy 5p, with trisomy of the distal part of 8p and of the centromeric region of chromosome 8. The clinical significance of de novo marker chromosomes is a major problem in prenatal counselling. Molecular cytogenetic tools such as FISH and microFISH are indispensable for characterizing markers and determining the breakpoints more precisely in deleted chromosomes.

Low prevalence of GAD and IA2 antibodies in schoolchildren from a village in the southwestern section of the Netherlands.

Glutamic acid decarboxylase (GAD) and insulinoma antigen 2 (IA2) antibodies are increasingly used as a tool to predict type I diabetes in children and as a differential diagnostic tool to distinguish type I and type II diabetes in adults. However, the background frequency of these antibodies in the general population has not been extensively studied and may differ between countries. The current study aims to establish the frequency of GAD and IA2 antibodies in an unselected population of schoolchildren and confirm the previously reported low prevalence of islet cell antibodies (ICA) in the general Dutch population. The study population consisted of 1403 unselected schoolchildren. All children were tested for GAD antibodies, and 1085 children were analyzed for IA2 antibodies by radiobinding assay. Development of diabetes was recorded during a 7-year follow-up. Five children (0.4%) were positive for GAD antibodies, one child (0.1%) was positive for IA2 antibodies. Two children developed diabetes during follow-up, one was positive for GAD antibodies only, the second was positive for both GAD and IA2 antibodies. The frequency of GAD and IA2 antibodies in the southwestern part of The Netherlands is low. This observation is in concordance with earlier studies on ICA in Dutch schoolchildren. For future diabetes prediction and intervention trials it is important to establish the background frequencies and predictive power of antibody screening in different populations.

Determinants of bone mineral content in childhood.

In a sample of 1190 children (574 boys and 616 girls), aged 6.8-10.7 years, bone mineral content was studied using quantitative röntgen microdensitometry (QMD) at the diaphyseal and the metaphyseal site of the left second digit. Percentile curves of bone mineral density was determined by skeletal age for boys and girls separately. Bone mineral content at the diaphyseal site was significantly associated with skeletal age, height and body weight in boys and girls and with chronological age at the metaphyseal site in boys. In girls higher levels of bone mineral content were observed in those with a skeletal age greater than 7.3 years, compared to those with a skeletal age equal to or less than 7.3 years, adjusted for height and body weight. In boys a higher level of bone mineral content was found in those with a height greater than 138 cm, adjusted for skeletal age, compared to those with a height equal or less than 130 cm, at the diaphyseal and metaphyseal site. Girls with a relatively higher body weight had lower levels of bone mineral content at the metaphyseal site.

Blood pressure in childhood: pooled findings of six European studies.

In an attempt to study and prevent the development of hypertension, there is a growing interest in measuring blood pressure in children. The aim of this is to detect and monitor those with a relatively high level of blood pressure. Until now, reference values on blood pressure in children are based on data from North-American youngsters. The present study provides percentile charts based on pooled data from studies on blood pressure conducted in six North-West European countries among 28,043 children. These blood pressure centiles are presented as age-, height- and gender-specific. Brief guidelines for blood pressure measurements in childhood and for detection of children with a relatively high blood pressure are included.

Determinants of blood pressure in the first decades of life.

The blood pressure (BP) in children has been studied since the beginning of this century, and in the past decade the potential association between childhood BP levels and adult hypertension has gained increasing interest. From several longitudinal studies, many of them comprising large numbers of children and youngsters, it appears that the BP of children is significantly associated with BP on follow-up measurements and that childhood BP is related to adult levels. Whether the objective is to predict future BP, or the aim is to shed light on the early pathogenesis of primary hypertension, it is of major importance to find out why BP rises in some and stays the same in others. To achieve this, characteristics need to be detected that are related to changes in BP in the first decades of life. Although not many reports on these dynamic relations are presently available, age, height, body weight, initial BP level, and a family history of hypertension have been put forward as determinants of children's BP change over time. Moreover, there are data to support the effect of dietary factors, most notably certain electrolytes, on BP regulation early in life. Also, certain hemodynamic and neural characteristics, such as changes in cardiac output and left ventricular mass, renal blood flow, and sympathetic nervous system activity, may be related to a subsequent rise in BP and future hypertension. Findings from nonexperimental and experimental studies on determinants of BP in children and youngsters will be reviewed.