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Multivariate analyses of the risk of insulin-dependent diabetes mellitus for siblings of insulin-dependent diabetic patients.

Multivariate models for the risk of insulin-dependent diabetes mellitus for siblings of patients with insulin-dependent diabetes were developed using logistic regression analysis. The individuals studied in this report are full siblings of the insulin-dependent diabetic patients diagnosed at Children's Hospital of Pittsburgh between 1964 and 1982. For all siblings considered together, the sharing of two (but not one) HLA haplotypes, the presence of insulin-dependent diabetes in a parent, and being relatively young at the time the proband in the family was diagnosed were significantly associated with increased risk. On the other hand, B7 + siblings had a significantly decreased risk compared to B7--siblings, indicating the presence of an HLA-linked protective gene for the development of the disease. There was a significant interaction between sharing two HLA haplotypes and maternal age at the time of birth; for non-HLA-identical siblings, risk increased with increased maternal age, but maternal age had little or no effect on the risk for HLA-identical siblings. When non-HLA-identical siblings (0 or 1 HLA haplotypes shared) were analyzed separately, only the presence of insulin-dependent diabetes in one of the parents and increased maternal age at the time of birth of the sibling were found to be significantly associated with increased risk. Both of the totally non-HLA-identical diabetic siblings (neither HLA haplotype shared) in this data set had a parent with insulin-dependent diabetes, indicating that at least one HLA haplotype must be inherited in common with an affected family member for diabetes to develop. For HLA-identical siblings, the significant variables were the age of the sibling when the proband was diagnosed, the possession of B7, and maternal age at the time of birth of the sibling, and all three were negatively associated with risk.

Adult↗

A contribution to the genetics of febrile seizures: waking and sleep EEG in siblings.

Waking and sleep EEGs were recorded in 67 siblings of 52 patients with febrile seizures (FS). Epileptic activity was noted in at least 1 sibling for 28 of the 52 patients (53.8%). Epileptic discharges were noted in 33 (49.2%) of the 67 siblings. Thirty-two siblings had 3-4 Hz spike wave complexes, and 1 sibling had independent centrotemporal spike foci (rolandic foci). Epileptic activity was noted exclusively in the waking state in only 3%, in waking and sleep in 31.3%, and only in sleep in 14.9%. The greatest number of epileptic discharges occurred in waking during hyperventatilation (32.8%) and during stage C sleep (38.8%). In 5 photosensitive siblings, additional epileptic discharges were noted in sleep in 1 and in waking and sleep in 4. At least 1 sibling in 5 (55.6%) of 9 patients with complicated febrile seizures, in 23 (53.5%) of 43 patients with simple FS, and in 4 of 9 patients (44.4%) with later onset epileptic seizures had seizure discharges. At least 1 sibling in 24 of 43 patients (55.8%) with exclusively FS in 13 of 30 (43.3%) male patients and in 15 of 22 (68.2%) female patients had seizure discharges. Siblings aged 6-10 years had (66.7%) the highest rates of activation. Epileptic discharges were noted in 83.3% of siblings with seizures, but in only 45.9% of siblings without seizures. Seizure activity was recorded in 68.2% of siblings who had occipital 3-4-Hz theta-delta-activity but in only 13.0% of siblings without this pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study.

OBJECTIVE: To test the hypothesis that non-diabetic dizygotic and monozygotic twin siblings of patients with type 1 diabetes have a similar high prevalence of islet cell autoantibodies, thus suggesting that islet cell autoimmunity is mainly environmentally determined. DESIGN: Prospective twin study. SETTING: Two specialist centres for diabetes in the United States. PARTICIPANTS: Non-diabetic monozygotic twin (n=53), dizygotic twin (n=30), and non-twin (n=149) siblings of patients with type 1 diabetes; 101 controls. MAIN OUTCOME MEASURES: Analysis of progression to diabetes and expression of anti-islet autoantibodies. RESULTS: Monozygotic twin siblings had a higher risk of progression to diabetes (12/53) than dizygotic twin siblings (0/30; P<0.005). At the last follow up 22 (41.5%) monozygotic twin siblings expressed autoantibodies compared with 6 (20%) dizygotic twin siblings (P<0.05), 16 (10.7%) non-twin siblings (P<0.0001), and 6 (5.9%) controls (P<0.0001). Monozygotic twin siblings expressed multiple (>/=2) antibodies more often than dizygotic twin siblings (10/38 v 1/23; P<0.05). By life table analysis the probability of developing positive autoantibodies was higher among the monozygotic twin siblings bearing the diabetes associated HLA DQ8/DQ2 genotype than in those without this genotype (64.2% (95% confidence interval 32.5% to 96%) v 23.5% (7% to 40%) at 10 years of discordance; P<0.05). CONCLUSION: Monozygotic and dizygotic twins differ in progression to diabetes and expression of islet cell autoantibodies. Dizygotic twin siblings are similar to non-twin siblings. These two observations suggest that genetic factors play an important part in determination of islet cell autoimmunity, thus rejecting the hypothesis. In addition, there is a high penetrance of islet cell autoimmunity in DQ8/DQ2 monozygotic twin siblings.

Adolescent↗

The consequences of antisocial behavior in older male siblings for younger brothers and sisters.

The contribution of younger male and female siblings' conflict and involvement in deviant activities with their older brothers to younger siblings' adolescent adjustment problems was examined in the context of parenting. Ineffective parenting during younger siblings' childhood had no direct effects on adjustment but facilitated their exposure to older brothers' deviant peers and activities. The effect of sibling conflict on adjustment was mediated by younger siblings' coparticipation in deviant activities with their older brothers during adolescence. Early sibling conflict and coparticipation in deviant activities synergistically increased the risk for younger siblings' adolescent adjustment problems. These empirical relations held in the context of parental discipline of younger siblings during adolescence. Sibling relationships entail a set of iterative social processes that strongly influence risk for adolescent antisocial behavior, drug use, sexual behavior, and traumatic experience. Variations in sibling influence were observed conditional on the gender combination of the sibling pair and on sibling age differences.

Adaptation, Psychological↗

Behavioural problems, social competence and self-concept in siblings of children with autism.

INTRODUCTION: This study investigated the psychological adjustment of siblings of children with high-functioning autism (HFA) in comparison with siblings of normally developing children in the domain of behavioural problems, social competence and self-concept. METHOD: Twenty-nine siblings of children with HFA and 29 siblings of children without a disorder participated in the study. Standardized, written questionnaires were used. RESULTS: Siblings of children with HFA, especially brothers and sisters between 6 and 11 years old, had more behavioural problems than siblings of the control group. Sisters of children with HFA ascribed higher social competence to themselves. Sisters of children with HFA between 12 and 16 years old had a more positive self-concept. In both groups siblings with a more negative self-concept had less social skills and siblings with a more positive self-concept scored better in the social domain. Finally, in accordance with the control group, the perception of the siblings' social competence of parents of children with HFA broadly matched the perception siblings had of themselves. DISCUSSION: Overall, siblings of children with HFA are not more susceptible to adaptation problems than siblings of children without a disorder. Implications for practice and further research are discussed.

Adaptation, Psychological↗

Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings.

AIM: We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings. METHODS: In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9; n = 132), or a control vaccine (meningococcus C vaccine; n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility. RESULTS: Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively; P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively; P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively; P < 0.001) and their younger siblings (19% vs. 13%, respectively; P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to > or =1, > or =2 and > or =3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls. CONCLUSION: The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.

Analysis of Variance↗

Sibling differentiation in adolescence: implications for behavioral genetic theory.

The presence of sibling "differentiating processes"--defined as processes in which increased sibling similarity in environmental or genetic factors leads to differences in sibling outcomes-poses a challenge for standard behavioral genetic theory and research. The presence of differentiation processes may affect estimates of genetic and environmental parameters in ways that have not been fully recognized. Utilizing data from the Nonshared Environment and Adolescent Development project, this study examined whether differentiating processes existed for seven composite indices of positive and negative adolescent adjustment. The 720 sibling pairs in the study were broken down into groups by age difference (0-4 years) between siblings. The hypothesis that siblings close in age would demonstrate lower correlations on adjustment measures was generally supported at two time points, three years apart. However, siblings one year apart at Time 1 were more similar to each other than were siblings two years apart, suggesting that shared environmental influences counteract sibling differentiation processes for these siblings. The overall trend supporting sibling differentiation was found to be unrelated to measures of sibling positivity and negativity.

Adolescent↗

Emotion regulation in context: the jealousy complex between young siblings and its relations with child and family characteristics.

Jealousy is a social emotion that has received little attention by developmental researchers. The current study examined sibling jealousy and its relations to child and family characteristics in 60 families with a 16-month-old toddler and an older preschool-age sibling. Sibling jealousy was elicited in social triads consisting of a parent (mother or father) and the two siblings. Positive marital relationship quality (i.e., love and relationship maintenance) was a particularly strong predictor of the older siblings' abilities to regulate jealousy reactions in the mother sessions. Younger siblings' jealous affect with mothers was linked to the child's temperament, whereas older siblings' jealous affect with mothers was related to the child's emotional understanding. Younger siblings displayed more behavioral dysregulation in the mother-sibling triads if there was greater sibling rivalry reported by mothers. Session order (i.e., which sibling was challenged first in the jealousy paradigm) had a strong effect on both the affect and behavioral dysregulation displayed by the older and younger siblings. Results are discussed with respect to the need for future research to consider social relationships as developmental contexts for young children's emotion regulation.

Child, Preschool↗

Sibling influences on childhood development.

To summarize the main points concerning sibling influence: 1. That siblings play a causal role in the development of aggressive behavior, in children's style of conflict behavior and in cooperative fantasy play is strongly suggested by recent research. 2. Marked problems in the sibling relationship are indicative of other problems, but a causal role for siblings is not established, other than for aggressive behavior. 3. Family factors are closely involved in the quality of sibling relationships--and thus in sibling influence, namely differential parental behavior, and the emotional climate of the family. That is, it is important not to consider the sibling relationship in isolation from other family relationships. 4. Studies of families under stress indicate heightened importance of these family factors. 5. It is likely, but not yet established, that later-born siblings are influenced by first-born in socio-cognitive development and gender identity. 6. Finally it should be noted that an important theme in current research on siblings is a concern with the question of why siblings develop to be so different from one another. It has been shown that the major source of environmental influence on the development of individual differences is within-family rather than between-family differences in experience (Plomin & Daniels, 1987). The different experiences each sibling may have within their relationship is one potential source of such differential environmental influence. Thus documenting the influence of siblings upon each other takes on added significance: By clarifying the extent and nature of this influence we will gain not only useful clinical information but illumination on a developmental principle of very general significance.

Aggression↗

Perceived support in sibling relationships and adolescent adjustment.

BACKGROUND: Siblings may support each other, but also reveal fierce rivalry and mutual aggression. Supportive sibling relationships have been linked to the development of psychosocial competence of children. In the present longitudinal study, we will focus on the development of perceived support in sibling dyads and on the influence of sibling support and sibling problem behavior on psychosocial adjustment in adolescence. METHOD: In a three-wave longitudinal sample of 285 Dutch families with two adolescent children (11- to 15-year-olds), these two siblings judged the support perceived from each other. In addition, they themselves and their parents judged their internalizing and externalizing problem behaviors. The relation of sibling support and sibling problem behavior with internalizing and externalizing problem behaviors was examined while controlling for support from parents and friends and, over time, controlling for the autoregressive effects of problem behavior. RESULTS: Support perceived from a sibling is mostly negatively related to externalizing problems; sibling problem behavior is strongly related to internalizing problems. Differential developmental trajectories of adolescents' adjustment are associated with siblings' support and problem behavior. CONCLUSION: The results indicate that adolescents' relationships with both older and younger siblings are characterized by modeling processes.

Adolescent↗

A longitudinal study of siblings of children with chronic disabilities.

OBJECTIVE: To examine the unaffected siblings of 2 different groups with chronic disabilities, pervasive developmental disorder (PDD) and Down syndrome (DS), over 3 years, comparing their adjustment with each other and with the siblings of a nondisabled group. METHOD: This study examines 137 siblings of children with PDD, children with DS, and developmentally normal children (control group) initially and 127 siblings at follow-up 3 years later. Their adjustment is measured by the Survey Diagnostic Instrument (SDI), completed by caregivers and teachers. Predictor variables include sibling self-perception, social support, and relationship with sibling, as indicated by siblings; caregiver psychosocial factors such as parental stress, caregiver depression, and marital relationship; family systems characteristics as viewed by both caregiver and sibling; and difficulty that disabled child causes as perceived by the primary caregiver. RESULTS: Significantly more adjustment problems are found in the siblings of PDD children at both times when compared with siblings of DS and control children. Caregivers of PDD children report the highest levels of distress and depression, and this persists over time. Parent distress was found, at both times, to be related to sibling adjustment problems, regardless of study group. CONCLUSION: These results have implications for preventive intervention for the unaffected siblings of PDD children.

Adaptation, Psychological↗

Environmental differences within the family and adjustment differences within pairs of adolescent siblings.

To what extent do siblings in the same family experience different parental treatment, sibling interaction, and peer relationships? Are such within-family experiential differences related to differences in the siblings' emotional adjustment? The present study explored these questions concerning within-family environment using data from 348 families that each included 2 siblings 11-17 years of age. The results indicate that siblings in the same family experience different environments, as reported by parents and to a larger extent by the siblings themselves. The results also demonstrate that within-family environmental differences are related to differences in development between siblings. Both the parent and sibling reports of the environment converge on the finding that the sibling who is more psychologically well adjusted (as reported by parents, siblings, and teachers) also experiences more maternal closeness, more sibling friendliness, more peer friendliness, more say in family decision making, and more parental chore expectations as compared to the other sibling.

Adolescent↗

Gaucher disease: variability in phenotype among siblings.

Although many mutations of the GBA gene have been described as causing Gaucher disease, there is generally poor correlation between genotype and phenotype, with a few exceptions. However, most previous reports of genotype-phenotype correlation have involved unrelated individuals, who, even if they share the same mutations, are not as genetically close as siblings. We have studied 24 groups (mostly pairs) of Canadian siblings with type I (non-neuronopathic) Gaucher disease. Since most Canadian provinces have adopted similar criteria for instituting enzyme replacement therapy (ERT), the age at which ERT is begun can serve as a rough surrogate for disease severity, and concordance (or lack of concordance) can be examined between siblings. In 14 of the 24 sibling families, there was sibling concordance: either both siblings were not on ERT, or both were on ERT and had begun at roughly the same age. In these families, there was also much similarity in the clinical features of the disease between siblings. In the other 10 families there was lack of sibling concordance, with only one sibling receiving ERT (or, in one family with three affected siblings, two of three on ERT). In these families, there was also much discrepancy between siblings in the clinical features (as might be expected in a setting where the guidelines for starting ERT are relatively uniform). Possible reasons for the discordances between siblings include macro-environmental and microenvironmental differences. The latter may include micro-environments at the level of the cell (e.g. lysosomal pH, alternative substrates) or at the level of the chromosome (contiguous genes, modifier genes, neutral polymorphisms in GBA).

Adolescent↗

Frequency and clinical pattern of celiac disease among siblings of celiac children.

To investigate the prevalence and clinical and genetic patterns of celiac disease (CD) among siblings of CD patients, 103 siblings and one twin of 80 celiac children were evaluated by means of their clinical history, physical examination, blood indices of nutritional status, and antigliadin antibodies (AGA). Antiendomysium antibody (AEA) levels were determined in 70 patients and 85 subjects were human leucocyte antigen (HLA) typed. On the basis of clinical or laboratory data or both, 21 siblings (20.2%) were submitted to intestinal biopsy, whereas intestinal biopsy in six siblings with positive serologic screening (AGA IgA or AEA or both) was not performed because of parental refusal. In a high percentage of cases (18%), all on a gluten-containing diet, the intestinal mucosa was atrophic, and CD was subsequently diagnosed. Because we could not submit all the siblings to intestinal biopsy, this figure could underestimate the real prevalence of the disease in our series; consequently, it was not possible to calculate accurately the sensitivity and specificity of AGA and AEA. Nevertheless, AEA (positive in all the nine siblings with mucosal atrophy), followed by AGA IgA, proved to be the best screening for CD. Eighteen of 19 CD siblings showed HLA-predisposing antigens. Among the 19 CD siblings, one showed a typical form with gastrointestinal symptoms, two had short stature, one suffered from recurrent vomiting, and in 15, the disease was clinically silent. On the contrary, among siblings who were first diagnosed (index cases), the majority (73.7%) had a typical form of CD, and no clinically silent cases were observed. We did not find any difference between index cases and CD siblings in food habits and distribution of HLA antigens. In 15 of 18 cases, the sibling diagnosed subsequently was the older one. Finally, the typical form of CD was significantly more frequent among the younger brother than the older. In conclusion, the high prevalence of the silent form of CD in our cases indicates that siblings of CD subjects should always be screened for CD. The combination of AGA IgA and AEA represent a good screening method to use in selecting children for the intestinal biopsy.

Celiac Disease↗

Islet cell-specific autoantibodies in children with insulin-dependent diabetes mellitus and their siblings at clinical manifestation of the disease. Childhood Diabetes in Finland Study Group.

The aim of this work was to characterize both newly diagnosed insulin-dependent diabetic subjects and their siblings with positive tests for islet cell-specific autoantibodies (ICSAA) and to evaluate whether there is an association between the ICSAA levels detected in the diabetic children and siblings. We analysed 781 probands younger than 15 years of age for islet cell antibodies (ICA) and 755 for insulin autoantibodies (IAA) and 610 of their 3-19-year-old non-diabetic siblings for ICA and IAA upon diagnosis of the proband. Islet cell antibodies were observed in 657 of the probands (84.1%) and IAA in 353 (46.8%). The ICA-positive probands were younger in age and had higher IAA levels than the ICA-negative probands, while the IAA-positive probands were younger and had higher levels of ICA than the IAA-negative probands. Islet cell antibodies were detected in 46 (7.5%) and IAA in 16 (2.6%) siblings, and the ICA-positive siblings had higher IAA levels than the ICA-negative siblings. A falling trend was seen in the frequency of ICA > or = 20 Juvenile Diabetes Foundation units in the siblings with decreasing degrees of HLA identity with the index case. Infections during the preceding year, especially respiratory infections, increased the prevalence of both ICA and IAA in the diabetic children at diagnosis and the frequency of IAA in the siblings. There was a significant, although weak, correlation between the IAA levels of the probands and those of their siblings when 594 pairs were tested (r(s) = 0.15; p < 0.001). No association could be seen between the ICA levels of the probands and those of their siblings, not even when including only HLA-identical proband-sib pairs in the analysis. The lack of any relation between ICA levels in the probands and siblings supports the view that there may be multiple exogenous factors capable of inducing ICA formation or else a common factor but variable responsiveness in the index case and the sibling.

Adolescent↗

Longitudinal study of fasting proinsulin in 148 siblings of patients with insulin-dependent diabetes mellitus. Study Group on Childhood Diabetes in Finland.

OBJECTIVE: To follow proinsulin immunoreactive material (PIM) in healthy siblings from the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) in the proband, for at least 2 years. DESIGN AND METHODS: The study comprised 148 siblings representing 112 families. The siblings were recruited from the nationwide 'Childhood Diabetes in Finland' study and tested for immunological markers. If a sibling was found positive for islet cell antibodies (ICA) or insulin autoantibodies (IAA), PIM sampling was extended beyond 2 years. RESULTS: Of the 148 siblings, 12 developed IDDM 3-53 months after the diagnosis in the proband. Eleven of these siblings exhibited initially normal PIM concentrations. In nine siblings, samples were available both more than 6 months and during the last 6 months before the diagnosis of IDDM; PIM concentrations increased in seven, remained unchanged in one, and decreased in one in the period up to the diagnosis of IDDM (P < 0.05). Median PIM concentration did not change significantly during the examination period of 2 years in the 136 siblings who did not contract IDDM. Constantly increased PIM concentrations were found in 12 of the 136 siblings who did not develop IDDM. These 12 siblings were all ICA negative. CONCLUSION: In healthy siblings of IDDM patients exhibiting an initially low PIM concentration, an abrupt increase in PIM seems to precede the clinical manifestation of IDDM within 0-6 months. However, there were too few patients available to close follow-up to allow calculation of any predictive value of this increase. Persistently increased PIM concentrations were present in some healthy siblings who did not develop IDDM. The reason for that finding remains unclear, but it could be associated with previous B cell damage.

Adolescent↗

Sibling relationships and behavior after pediatric traumatic brain injury.

To evaluate long-term outcomes for siblings of children with traumatic brain injury (TBI), measures of sibling relationships and sibling behavior were collected an average of 4 years postinjury. The study sample included participants in a larger longitudinal study who had school-aged siblings, including 34 with severe TBI, 30 with moderate TBI, and 39 with orthopedic injuries not involving brain insult (ORTHO group). Group comparisons revealed more negative sibling relationships in families of children with TBI than in families of children in the ORTHO group, but only for mixed-gender sibling pairings. Behavior problems in children with TBI predicted both sibling relationships and sibling behavior problems. The findings indicate a need to monitor the adjustment of siblings and sibling relationships after TBI and to include siblings in family interventions.

Adaptation, Psychological↗

Siblings of disabled children: birth order and age-spacing effects.

Whereas older siblings of children with congenital disability have lived their earliest years in a "normal" family environment, younger siblings, especially those in a close age-spacing relationship, were born into families marked by the presence of a disabled child. In this paper, 327 siblings of disabled children are compared to 248 siblings from a random sample of families to examine whether the early family environment of siblings of disabled children, as indexed by relative birth order and age-spacing, has a unique influence on psychological functioning. The findings partially confirmed the expected relationships: Younger male siblings, specifically those in close age-spacing relationship to the disabled child, scored higher on psychological impairment than older male siblings. Among female siblings, a similar influence was not in evidence: Younger female siblings were psychologically better off than older female siblings and their age-spacing was not significantly related to psychological functioning. However, the results suggest that siblings' later response to early life experience may be sex-contingent, with males demonstrating interpersonal aggression and females experiencing depressive-anxious feelings.

Adaptation, Psychological↗