Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed by subtelomere fluorescence in situ hybridization (FISH), are a significant cause of idiopathic mental retardation (MR). Some 20 subtelomere studies, including more than 2,500 subjects, have been reported. The studies are not directly comparable because different techniques and patient ascertainment criteria were used, but an analysis of 14 studies showed that aberrations were detected in 97 out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 4.60-6.84%). We performed a subtelomere FISH study of 50 unrelated children ascertained by a checklist that evaluates MR or developmental delay, dysmorphism, growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced familial translocations or inversions, two unbalanced de novo translocations, and two de novo deletions. Patient 5 showed multiple anomalies (large head, vision defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect, mild transient homocysteinemia) and a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced rearrangement associated with a disease phenotype is a novel one. FISH mapping using panels of overlapping BAC clones identified a number of candidate genes at or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and three genes of unknown function at 20q13.33. Only the homocysteinemia could be speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified degree of MR tested positive, suggesting that the checklist approach could be especially useful within this group of patients.

The purpose of this study was to establish the first-trimester screening for Down syndrome (DS) in Estonia and to evaluate the potential of a contingent screening in the population of pregnant women. A prospective cohort study included non-selected pregnancies during the programme of first-trimester screening for DS in a 4-year period at a single centre. The following screening tests were evaluated: measurement of nuchal translucency (NT) and serum screening [pregnancy-associated plasma protein A and free beta subunit of human chorionic gonadotropin (fβ-HCG)]; results were given as combined screening. After first-trimester screening, contingent screening protocol was used, and women were divided into three groups: high risk, low risk and an intermediate risk group. In the last group, a second-trimester triple test (AFP; total HCG and uE3) was also performed. The study group consisted of 3,194 non-selected pregnancies. In 1,387 (43.4%) women, first-trimester serum screening showed low risk (risk ≤ 1:5,000), and no future testing was performed, in 30 (0.9%) women screening test showed high risk (risk≥1:50) and a diagnostic test was offered, and in 1,777 (55.7%) women repeated risk calculation in the second trimester was done. During the study period, there were 17 cases of trisomy 21, of which 15 (88.3%) were detected with the described screening programme. In conclusion, two-step contingent sequential screening is a better choice for Down syndrome screening in Estonia instead of previously used second-trimester screening, and it offers the advantage of earlier diagnosis.

The aim of the study was to investigate the livebirth prevalence of Down's syndrome (DS) in Estonia during the past 14 years, create a DS database and observe the effectiveness of prenatal screening. This is a population-based descriptive study. The study subjects were children with DS diagnosis born between the years 1990 and 2003. We collected data from genetic centres in Estonia, from the databases of DS support groups, from institutions for disabled children and from the registers of family doctors/paediatricians. Prenatal screening for chromosomal anomalies for women aged >or=35 years was started in Estonia in 1995. Therefore, we divided the DS children into two groups: 112 born between 1990 and 1994 comprise group I, and 127 born between 1995 and 2003 comprise group II. Group II was further divided into two subgroups: IIa, from 1995 to 1998, when screening of advanced maternal age (>or=35 years) commenced, and IIb, from 1999 to 2003, when screening of second trimester maternal serum for younger women commenced. Prenatally, 68 cases of DS were diagnosed between 1995 and 2003 in the whole of Estonia, and all of these pregnancies were terminated. This represents 34.9% of all delivered and prenatally detected DS cases from this period. The overall livebirth prevalence was 1.17 per 1000 livebirths. The livebirth prevalence in group I was 1.25 and in group II was 1.09 per 1000 livebirths. The second trimester maternal serum screening with advanced maternal age screening was more effective than advanced maternal age screening alone. The livebirth prevalence in group IIa was 1.22 and in group IIb 0.99 per 1000 livebirths. Overall, regular trisomy was found in 90.4%, translocation in 6.3% and mosaicism in 2.9%. The overall male to female sex ratio of DS was 1.09.

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Objective: To investigate whether chromosomally normal fetuses with marked changes in maternal serum markers and first trimester ultrasound NT marker have an increased risk of congenital anomalies or delayed development at 2 years of age. Methods: Screening tests of 5257 pregnant women were analyzed during a one-year period. Significant changes in biochemical and/or ultrasound markers were documented in 138 pregnant women, whereas positive risk calculation for chromosomal anomalies was evident in 74 of them, who were included in our study. Postnatal study group included 35 children born from mothers with marked changes in screening tests. Results: Among the 74 pregnant women, a structural or genetic abnormality was diagnosed in 16 cases (21.6%), fetal death occurred in 12 cases (16.2%) and child was healthy at the age of 2 years in 31 cases (41.9%). In 3/4 of the cases, a pathology was diagnosed prenatally, while the remaining 1/4 were discovered postnatally. Four children had with congenital anomalies and/or syndromes: two had congenital heart disease-atrial septal defect and ventricular septal defect with patent ductus arteriosus, one Silver-Russell syndrome and one congenital adrenal hyperplasia. It was not possible to get the final information about outcome in 15 cases (20.3%). Conclusions: Children born to these mothers should be actively followed by a pediatrician or clinical geneticist for additional investigations after birth as they have a risk of 5.4% of having a congenital or genetic abnormality.

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