Nonspecific inherited risk factors for acute respiratory diseases in children living in the western part of the Baikal-Amur railway

Variation of 9 polymorphic loci was compared in 2 groups of children from Russian native and migrant population of Western area of Baikal-Amur Railway--those who suffered from acute respiratory diseases during first year of life and their parents, and normal children and their parents. Frequencies of genotypes 1-1 (HP locus). 00 (ABO locus), and pp (F locus) were significantly higher in normal children than in the affected ones. Heterozygosity observed in native parents of the diseased children was lower as compared with other groups. It was possible to distinguish two groups, according to the degree of genic similarity: the first one included healthy children and their parents from migrant and native population, the second one included all affected children and their parents. Significance of association between phenotypes at 3 loci (HP, ABO, P) and predisposition of the children to acute respiratory diseases were evaluated. A conclusion was made that in children of both migrant and native Russian parents similar combinations of anthropological traits and gene markers are the factors of their nonspecific resistance to acute respiratory diseases.     

Aminoacid profile and oxidative status in children affected by Down syndrome before and after supplementary nutritional treatment

Down syndrome is the most common autosomal aberration among liveborns, characterised by several clinical features and metabolic disturbances. Aminoacid pathways abnormalities and defective oxidative balance are the most common metabolic problems in Down Syndrome. To evaluate the biochemical responses of children with Down Syndrome to a nutritional regimen supplemented with aminoacids, vitamins and polyunsaturated fatty acids, we submitted 86 subjects divided in two groups (0-6 and 6-12 years) to the dosage of plasma levels of aminoacids, antioxidant enzymes activities and reactive oxygen species, before and after 12 months of such nutritional supplementation and in relation to normal controls. The results obtained showed a tendency towards the values of normal subjects with statistically significant differences. Although other studies must be performed to confirm and define such report, our experience supports the usefulness of a nutritional supplementation with aminoacids, vitamins and polyunsaturated fatty acids, also considering the absence of side effects.     

alpha 1-Antitrypsin quantitative and qualitative (Pi phenotyping) characterization in Down syndrome subjects and in their parents.

Quantitative characterization and alpha 1-antitrypsin (alpha 1AT) Pi phenotyping by isoelectric focusing (IEF) and immunofixation electrophoresis (IFE) were done on 84 patients with trisomy 21, divided into two groups, and on their parents. Group A consisted of 42 subjects whose parents were less than 30 years at the time of the patient's birth; group B, of 42 subjects whose parents were more than 35 years. The results were compared with those found in a group of normal subjects. Statistical analysis of the Pi phenotype distribution and the frequency of variant phenotypes does not support a causal relationship between the Pi phenotype and the chromosomal errors responsible for Down syndrome.     

Decreased HLA heterogeneity in parents of children with Down syndrome.

HLA-A and B antigens were determined in a study of 37 couples and their children with trisomy 21 Down syndrome (DS), using a standard microlymphocytotoxicity test. The comparison groups included 76 couples and their healthy children. All individuals were Caucasians from the same geographical area, and there was no history of consanguinity. The parents of children with DS did not show an association with a specific HLA antigen or haplotype. Sixteen of the 37 couples (43.24%) having children with DS share two or more antigens at the A and/or B locus. This was significantly higher than the proportion in the control group (6/76, or 7.88%). Of the 16 couples having children with DS and sharing two or more antigens, eight had a haplotype in common, in contrast with only two couples in the control group. The data suggest that sharing of parental HLA-A and B antigens may be related either to the occurrence of trisomy 21 zygotes or to prenatal survival of affected embryos and fetuses.     

Parental quality of life in the framework of paediatric chronic gastrointestinal disease

Chronic gastrointestinal diseases, such as inflammatory bowel disease (IBD) and celiac disease (CD), might have impact not only on the affected child but also on their parents since inside the family framework, a change in each member may have influence on the whole system. The aim of this study was to test the hypothesis that parents whose children have IBD or CD will have a lower quality of life (QoL) compared to parents of healthy children, as well as that lower QoL will be found among parents who perceive lower health related quality of life (HRQOL) of their child. 55 parents of children with IBD, 49 of CD and 53 parents of healthy children were included in the study. Children were aged 7-18 years. In order to measure parental QoL, a Croatian version of the WHOQOL-BREF questionnaire was administered, with four domains: physical health, psychological health, social relationship and environment. The Total QoL was calculated as a sum of all domain items. The parent-proxy report of children's HRQOL, PedsQL 4.0 Generic Core Scales was used. Main result shows that parents of children with IBD report a significantly lower psychological health, compared to parents of other children, and significantly lower physical health compared to parents of healthy children. Among parents of children with CD and parents of healthy children, better parental Total QoL was significantly correlated with better parental report of children's HRQOL, while for parents of children with IBD those associations were not found. Results of study show association between presence of the disease in offspring with poorer parental QoL, thus highlight the importance of supporting not only children with chronic disease but also involving their parents in psychosocial interventions, as well as supporting the patient's association groups which gather both children with chronic disease and their parents.     

The distorted shell method for clustering for syndrome classification.

Syndrome classification may be described as the arrangement of individuals into groups on the basis of their phenotypic resemblance. This paper describes how phenotypic resemblance may be quantified and demonstrates a numerical method called distorted shell clustering, which isolates groups of phenotypically similar individuals representing syndromes. This new method takes into consideration apparent biological properties of syndromes. It allows for overlapping phenotypes between syndromes, and differing character association and variability within syndromes. This method is compared to four other clustering methods by using suspects for a syndrome of known etiology (Down syndrome). The numerical results based on the phenotype then can be compared with the actual diagnosis. Only the distorted shell method classifies patients, without error, into two major clusters: the Down and the non-Down, while maintaining a high level of efficiency.     

A low rate of trisomy 21 in twin-pregnancies: a cytogenetics retrospective study of 278 cases

From January 1st 1990 until December 31st 2001, we collected 19686 prenatal diagnosis (on amniocentesis and chorius villus sampling). Five hundred twelve samples (2.6%) concerned 278 twin pregnancies. The most frequent indications were maternal age > or = 35 years (108/278 = 38.8%), medically assisted procreation (34/278 = 12.3%), positive ultrasound (20/278 = 7.2%). Chromosome abnormalities were found in eight twin-pregnancies (2.9%): five with only one fetus affected [47,XX,+ 18; 45,XX,t( 13;14); 47,XYY; 47,XXX; 45,XX, t(13;14)], two with both fetuses showing the same chromosomal abnormality [inv(11)(q21q25); 47,XX,+ 18] and one with only one fetus tested [47,XX,+ 18]. In total, we found eight autosomal abnormalities, four inherited balanced rearrangements (two robertsonian translocations and two paracentric inversions of chromosome 11) and four trisomies 18. We also observed two sex chromosome abnormalities interesting only one of the two fetuses. Surprisingly, we did no detect any Down Syndrome among this population. The frequency of Down Syndrome was significantly (p < 0.05) lower in our population of twin pregnancies (0.0%) as compared to the observed incidence in singleton pregnancies during the same period (163/19162 = 0.9%).     

Frequency of consanguineous marriages among parents and grandparents of Down patients

Summary The existence of a rare autosomal gene which in the homozygous state would cause mitotic nondisjunction in the Down zygote has been hypothesized in the past by Alfi et al. (1980). This hypothesis can be supported or contradicted by the study of the frequency of consanguineous marriages among parents of affected children. Our study on 242 children affected with Down syndrome does not show any increase in the frequency of consanguineous marriages among their parents with respect to the general population, and therefore does not support the hypothesis of an autosomal gene controlling mitotic nondisjunction. Our data do not show any increase in the frequency of consanguineaous marriages even among paternal and maternal grandparents of the affected children, thus not supporting the other possible explanation of an autosomal recessive condition in one of the patient's parents which would cause meiotic nondisjunction.     

Pedometer-determined physical activity levels of healthy children and children with Down’s syndrome

Purpose: Children with Down’s syndrome (DS) are considered sedentary and less engaged in recommended physical activity (PA) levels. This study compared the PA levels between children with DS and healthy children in Saudi Arabia.

Methods: The study included 85 children divided into two groups. The DS group comprised 37 children with DS aged 8–12?years recruited from the Down Syndrome Charitable Association and Al-Nahda Schools for DS. The healthy group comprised 41 healthy children aged 8–12?years recruited from regular schools in the same region. PA levels were measured over 7?days using a pedometer.

Results: The healthy group was more active than the DS group (p?p?p?Conclusions: The DS group had a high body mass index and physical inactivity compared with the second group. Obesity and physical inactivity among Saudi Arabian children with and without DS are major health concerns. Therefore, concerted efforts are needed to combat childhood obesity, promote PA, improve patient quality of life, and reduce the sedentary lifestyle among Saudi children and adolescents.     

Familien mit geistig behinderten Kindern

When a child is born with a mental handicap, his or her parents are usually confronted with a complicated and demanding process of adaptation and emotional coping, as well as with profound restructuring of their family life. Professional experts, including physicians and psychosocial specialists, can support the parents in terms of supplying them with information, but they inherently lack the experience of parents who have equally affected children and who have learned to master everyday problems and challenges. Filling that gap is the main purpose of self-support groups, whose number and importance have continuously grown since the 1970s. Internet databases are valuable signposts to self-support groups concerning particular, and even rare, types of handicaps. A study on Down syndrome exemplifies the self-support group experiences of parents of mentally retarded children. We conclude with suggestions for better conjunction of professional and self-support activities.     

A cephalometric study in Rubinstein-Taybi syndrome

A roentgencephalometric study to compare the facial morphology of 18 individuals affected with Rubinstein-Taybi syndrome and 25 of their parents was performed. The main findings in the affected individuals were shortening of facial height and depth, cranial base length, a marked decrease in size of the mandible, and a steep cranial base. A change with age was found for some dimensions. The pattern variability indices were high, indicating an abnormal craniofacial profile. The correlations between most patients were high, although this was less expressed for the younger patients. The parents had a normal pattern profile and pattern profile variability indices. The correlation between parents and their affected children was low. This study suggests that pattern profile analysis of cephalometric measurements may be a useful diagnostic tool in Rubinstein-Taybi syndrome. However, comparable studies of large groups of patients, especially of a younger age, are needed for further ascertainment of normal values in individuals with Rubinstein-Taybi syndrome at different stages of facial development.     

Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down Syndrome screening

Background

As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target.

Methodology/Principal Findings

Placenta and fetal liver at 15.5 days gestation were analyzed by microarray profiling. We confirmed increased expression of genes located at the trisomic chromosomal region. Overall, between the two genotypes more differentially expressed genes were found in fetal liver than in placenta. Furthermore, the fetal liver data are in line with the hematological aberrations found in humans with Down Syndrome as well as Ts1Cje mice. Together, we found 25 targets that are predicted (by Gene Ontology, UniProt, or the Human Plasma Proteome project) to be detectable in human serum.

Conclusions/Significance

Fetal liver might harbor more promising targets for Down Syndrome screening studies. We expect these new targets will help focus further experimental studies on identifying and validating human maternal serum biomarkers for Down Syndrome screening.     

Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome

We have analyzed the survival motor neuron gene (SMN1) dosage in 100 parents of children with homozygous SMN1 deletions. Of these parents, 96 (96%) demonstrated the expected one-copy SMN1 carrier genotype. However, four parents (4%) were observed to have a normal two-copy SMN1 dosage. The presence of two intact SMN1 genes in the parent of an affected child indicates either the occurrence of a de novo mutation event or a situation in which one chromosome has two copies of SMN1, whereas the other is null. We have separated individual chromosomes from two of these parents with two-copy SMN1 dosage by somatic cell hybridization and have employed a modified quantitative dosage assay to provide direct evidence that one parent is a two-copy/ zero-copy SMN1 carrier, whereas the other parent had an affected child as the result of a de novo mutation. These findings are important for assessing the recurrence risk of parents of children with spinal muscular atrophy and for providing accurate family counseling.     

Parental trisomy 21 mosaicism.

A family with three children with trisomy 21 in which the mother is a phenotypically normal, trisomy 21/normal mosaic was studied. Chromosome 21 fluorescent heteromorphisms were used to document that two of the three number 21's in two of the Down syndrome offspring were of maternal origin. Five cytogenetic surveys in which both parents of a child with trisomy 21 were studied have been reviewed. From these data, it is estimated that 3% of couples producing a child with trisomy 21 can be explained by parental mosaicism. From 17 informative sibships, with one parent mosaic, the segregation ratio was estimated to be 0.43 +/- 0.11.     

Trisomy 21 Down syndrome

Summary In a series of 374 families with Down syndrome progeny, structural chromosome rearrangements were detected in the parents of six children with regular trisomy. The aberrations were reciprocal translocations and inversions. In all three informative families, the parent who transmitted the extra chromosome was not the one with the structural rearrangement. Among the three non-informative families there was one in which both parents carried different reciprocal translocations. In two other families a chromosome aberration was detected: a triple X mother and a father with a Philadelphia chromosome. Omitting the four parents with possible biased asccrtainment, 0.4% had a chromosome rearrangement. When the parents with constitutional chromosome aberrations and those with mosaicism, described previously, are combined, the frequency of chromosomally abnormal parents lies between 1.9% and 3.2%. When correlated with parental transmission of the extra chromosome, mosaicism rather than structural rearrangements appears to be of ctiologic significance.     

Recurrence risks for down syndrome

Summary The recurrence risks for Down syndrome due to an inherited translocation are estimated from empirical data in the literature for two maternal age groups: mothers under 30 and mothers 30 and over. These risks were found to be approximately 0.3% and 0.05%, respectively. The probability for two Down syndrome sibs both having an inherited translocation was estimated as about 18.2% for the former age group and 2.7% for the latter. The relative effectiveness in preventing Down syndrome births by karyotyping affected children is discussed.     

Personality profiles of youngsters with velo-cardio-facial syndrome

The personality profile of 48 youngsters (24 males and 24 females, mean age 8 years, 5 months) with Velo-Cardio-Facial Syndrome (VCFS) was compared with a group of 240 non VCFS control youngsters (matched on age and gender), and, in addition, with groups of youngsters with Prader-Willi (PWS), Fragile X (FXS), and Williams Syndromes (WS). Personality characteristics of each youngster were rated by both parents, using the California Child Q-set (CCQ). The scores on eight personality dimensions were compared, i.e., Extraversion, Agreeableness, Conscientiousness, Emotional Stability, Openness, Motor Activity, Irritability, and Dependency. Moreover, Individual differences in personality of VCFS youngsters were related to IQ level, presence or absence of cardiac defects, and de novo versus familial origin of VCFS. The personality profile of VCFS youngsters was markedly different from all non-VCFS groups. Compared to the 240 control children, they were equally extravert and agreeable, less conscientious and emotional stable and more Irritable and dependent. Some personality characteristics in youngsters with VCFS were related to IQ and Age, but not to cardiac defects or de novo versus familial genetic origin of the 22q11 deletion.     

Social perceptions of the effects of Down syndrome facial surgery: a school-based study of ratings by normal adolescents

This study examines how 277 normal adolescents from five Israeli schools perceive the Down syndrome face before and after plastic surgery. A seven-point Likert scale was used to rate slides of normal and Down syndrome faces on four dimensions. Down syndrome patients were seen as less attractive, intelligent, good-hearted, and socially appealing than normal individuals. The slides were in nonapparent order and contained preoperative and 1-year postoperative views of eight plastic surgical patients. Paired t tests were used to examine operative changes, and all four dimensions showed overall postoperative improvement (p less than 0.001), but case-to-case variation was considerable. A linear relationship was found between change in appearance ratings and change in intelligence ratings. Findings suggest that when improvements in facial appearance are realized, peer normal social perceptions of the Down syndrome child may be enhanced. The relationship between school placement, intellectual level, and surgical decision making is discussed.     

Hopelessness of mothers who have children with Down syndrome

This study was conducted to determine hopelessness status of mothers who have children with Down syndrome. Beck Hopelessness Scale was used in this restrictive type study. The average value of mothers enrolled in the study was detected as 8.29 +/- 2.49. Age, education level, socio-economical status, work and the problems between parents were also examined and it was found that there is a relationship between the education level, socio-economical status, the problems between parents and the hopelessness scale (p < 0.01). Consequently, it is apparent that the mothers who have children with Down syndrome need social and psychological support to overcome their feelings of hopelessness.