Behavioral assessment of psychopathology in children: infantile autism

The utility of a subtest of 14 items from the Children's Psychiatric Rating Scale (CPRS) for evaluating psychopathology in autistic children was examined. A series of 180 autistic children, who satisfied the DSM-III criteria for Infantile Autism, Full Syndrome Present, were rated on the CPRS. A series of children with conduct disorder diagnoses were added to provide a contrast group for investigating specificity of behavioral manifestations with regard to autism. Multivariate analysis was used to elucidate major behavioral dimensions, to identify distinct subtypes, and to evaluate discriminant validity of the CPRS behavioral ratings.     

A developmental assessment chart for non-institutionalized Down syndrome children.

This prospective study was undertaken to present a test form utilizing the same test items as the Denver Developmental Screening Test in categories of personal-social, fine motor-adaptive, language, and gross motor attainment comparing the performance of an individual Down Syndrome child with that of similar children on whom the items were standardized. A developmental assessment chart was constructed based on 96 consecutive home-reared Down syndrome children (2 months to 8 years). This chart can be easily administered and the developmental status of a particular Down syndrome child evaluated.     

Acute leukemias in children with Down syndrome

Children with Down syndrome (DS) often present with hematopoietic abnormalities, and are at increased risk of developing leukemia. Specifically, 3-10% of newborns with DS are diagnosed with transient myeloproliferative disease, and children with DS are 500 times more likely to develop acute megakaryoblastic leukemia (AMKL) and 20 times more likely to develop acute lymphoblastic leukemia (ALL) than typical children. This review examines the characteristics of these leukemias and their development in the unique genetic background of trisomy 21. A discussion is also provided for areas of future research and potential therapeutic development.     

Caries in Portuguese children with Down syndrome

OBJECTIVES:

Oral health in Down syndrome children has some peculiar aspects that must be considered in the follow-up of these patients. This study focuses on characterizing the environmental and host factors associated with dental caries in Portuguese children with and without Down syndrome.

METHODS:

A sibling-matched, population-based, cross-sectional survey was performed.

RESULTS:

Down syndrome children presented a significantly greater percentage of children without caries, 78% vs. 58% of non-Down syndrome siblings. This difference in the DMFT index (number of decayed, missing and filled teeth) essentially reflects data obtained from treated teeth, for which 91% of children with Down syndrome had never had a tooth treated vs. 67% of siblings. This result was statistically significant, whereas results for decayed and lost teeth did not differ between Down syndrome children and their unaffected siblings. Additionally, in Down syndrome children, a delayed eruption of the second molar occurs. Down syndrome children and their siblings have similar oral hygiene habits, but a higher percentage of Down syndrome children visit a dentist before the age of three years, in comparison to their siblings. Bruxism was also more common in Down syndrome children compared to their siblings.

CONCLUSIONS:

Our results show that Portuguese children with Down syndrome have lower caries rates than children without Down syndrome. This reduced prevalence may be associated with the parents'' greater concern about oral health care in Down syndrome children, resulting in their taking them sooner to visit a dentist, as well as to a higher bruxism prevalence and delayed tooth eruption.     

Survival of children with Down syndrome in Italy

A cohort of 917 Down syndrome (DS) children born in Italy between 1978 and 1984 was studied for survival through the age of 8 years. The highest mortality occurred in the first month of life (7.9%); survival was about 80% at 1 year, 78% at 2 years, and 76% at 5 years, with small decreases thereafter. At the univariate analysis, survival was lower for subjects with congenital heart disease (CHD), birth weight <2,500 g, parity of 3 or plus, maternal age ≥35 years, and for those born in Southern Italy compared with Northern Italy. No differences in survival were observed by sex and by socioeconomic status. The Cox proportional hazard model was used to evaluate the effect of each variable adjusted for all the others present in the model. Presence of CHD (odds ratio = 3.27; 95% confidence interval (C.I.) 2.31–4.63), birth in the South (odds ratio = 2.69; 95% C.I. 1.91–3.79), and low birth weight (odds ratio = 1.87; 95% C.I. 1.29–2.72) were independently associated with survival. None of the other variables emerged as a statistically significant prognostic factor. Various hypotheses were considered to interpret the unexpected effect of place of birth on survival. Quality of medical care provided in the South of Italy is the most likely determinant of the high mortality observed among children with DS born in that area of Italy. Such differences in survival within the same country could occur in other developed nations as well.     

Detection of iron deficiency in children with Down syndrome

PurposeCurrent American Academy of Pediatrics guidelines for children with Down syndrome (DS) recommend a complete blood count (CBC) at birth and hemoglobin annually to screen for iron deficiency (ID) and ID anemia (IDA) in low-risk children. We aimed to determine if macrocytosis masks the diagnosis of ID/IDA and to evaluate the utility of biochemical and red blood cell indices for detecting ID/IDA in DS.MethodsWe reviewed data from 856 individuals from five DS specialty clinics. Data included hemoglobin, mean corpuscular volume, red cell distribution width (RDW), percent transferrin saturation (TS), ferritin, and c-reactive protein. Receiver operating characteristic curves were calculated.ResultsMacrocytosis was found in 32% of the sample. If hemoglobin alone was used for screening, all individuals with IDA would have been identified, but ID would have been missed in all subjects. RDW had the highest discriminability of any single test for ID/IDA. The combination of RDW with ferritin or TS led to 100% sensitivity, and RDW combined with ferritin showed the highest discriminability for ID/IDA.ConclusionWe provide evidence to support that a CBC and ferritin be obtained routinely for children over 1 year old with DS rather than hemoglobin alone for detection of ID.     

Survival of children with Down syndrome in Italy.

A cohort of 917 Down syndrome (DS) children born in Italy between 1978 and 1984 was studied for survival through the age of 8 years. The highest mortality occurred in the first month of life (7.9%); survival was about 80% at 1 year, 78% at 2 years, and 76% at 5 years, with small decreases thereafter. At the univariate analysis, survival was lower for subjects with congenital heart disease (CHD), birth weight less than 2,500 g, parity of 3 or plus, maternal age greater than or equal to 35 years, and for those born in Southern Italy compared with Northern Italy. No differences in survival were observed by sex and by socioeconomic status. The Cox proportional hazard model was used to evaluate the effect of each variable adjusted for all the others present in the model. Presence of CHD (odds ratio = 3.27; 95% confidence interval (C.I.) 2.31-4.63), birth in the South (odds ratio = 2.69; 95% C.I. 1.91-3.79), and low birth weight (odds ratio = 1.87; 95% C.I. 1.29-2.72) were independently associated with survival. None of the other variables emerged as a statistically significant prognostic factor. Various hypotheses were considered to interpret the unexpected effect of place of birth on survival. Quality of medical care provided in the South of Italy is the most likely determinant of the high mortality observed among children with DS born in that area of Italy. Such differences in survival within the same country could occur in other developed nations as well.     

Survival of children with Down syndrome in South America

The first step of all healthcare actions aimed at promoting an appropriate quality of life for infants affected by Down syndrome (DS) is to ensure their survival. This investigation was aimed at estimating the infant mortality rate of infants affected with DS in urban populations of South America. Thirty-three hospitals included in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) distributed in 23 cities of 5 South American countries followed 360 liveborn DS cases born during the 1988–1992 period. Families were recontacted after the infant should have reached the age of one year. The collected data included information about health status; i.e., frequency and dates of diagnosed illnesses and hospital admissions, and, in case of death, information on date, place and cause of death, and illness immediately before death. Information about the interviews included place, date, and name of the interviewer. A closed questionnaire was employed by the interviewers, mostly physicians, nurses, and social workers. Life table analysis up to the age of one year was performed by the actuarial survival method. The overall mean survival at age one year was 0.736 (SE = 0.023). Thirty-three (9.2%) of the 360 cases died neonatally, and 62 (17.2%) within the remaining 2-to-12-month interval. The probability of survival at one year of age did not differ between public (209 cases; mean 0.718; SE = 0.031) and private (151 cases; mean: 0.762; SE = 0.035) (χ²:0.87; df:1; P >0.05) health systems. The 150 DS cases with a congenital heart defect (CHD) had a significantly lower P robability of survival at the age of one year (mean: 0.660; SE: 0.039) than did the 210 cases without CHD (mean: 0.790; SE: 0.028) (χ²:6.67; df:1; P <0.01). The death rate in the first year of life for DS cases without a detected cardiac defect (21%) is significantly higher than that reported in developed countries; namely, 16% from Italy, 11% from Canada, 10% from England, and 7% from Denmark. Am. J. Med. Genet. 79:108–111, 1998. © 1998 Wiley-Liss, Inc.     

Altered endotoxin responsiveness in healthy children with Down syndrome

Background

Down syndrome (DS) is the most common syndromic immunodeficiency with an increased risk of infection, mortality from sepsis, and autoinflammation. Innate immune function is altered in DS and therefore we examined responses in CD11b and Toll like receptor 4 (TLR-4), which are important immune cell surface markers upregulated in response to Lipopolysaccharide (LPS) endotoxin, and the immunomodulator melatonin. Neutrophil and monocyte responses to LPS and melatonin in children with Down syndrome (DS) who were clinically stable were compared to age-matched controls. Whole blood was incubated with LPS and melatonin and the relative expression of CD11b and TLR-4 evaluated by flow cytometry.

Results

Children with DS had an increased response to LPS in neutrophils and intermediate monocytes, while also having elevated TLR-4 expression on non-classical monocytes compared to controls at baseline. Melatonin reduced CD11b expression on neutrophils, total monocytes, both classical and intermediate sub-types, in children with DS and controls.

Conclusion

Melatonin could represent a useful clinical adjunct in the treatment of sepsis as an immunomodulator. Children with DS had increased LPS responses which may contribute to the more adverse outcomes seen in sepsis.

     

New onset focal weakness in children with Down syndrome

New onset focal weakness is relatively common in patients with Down syndrome (DS), and has broad differential diagnosis. Ten cases of new onset focal weakness in patients with DS were encountered or are currently being followed in two DS clinics, with a combined population of patients of approximately 850, for a clinic population prevalence of 1.2%. The median age at presentation was 4 years old (range 1 month-44 years). The causes of new onset focal weakness were: stroke from Moyamoya disease (two patients); stroke from vaso occlusive disease (one patient); stroke from venus sinus thrombosis (one patient); traumatic subdural hematoma (one patient); brain abscess (one patient); spinal cord injury (SCI) from cervical spinal stenosis (two patients); SCI from atlantoaxial instability (AAI) (one patient); and brachial plexus injury (one patient). Of the 10 patients with focal weakness, 8 had potentially treatable conditions, and 5 had surgery. The differential diagnosis of new onset focal weakness in DS is broad, with diseases reported involving all levels of the nervous system from brain to muscle. For some diagnoses, expeditious diagnosis may improve outcome.     

Chromosome 7 abnormalities in children with Down syndrome and preleukemia

Three children, two boys and one girl, with Down syndrome (DS) who presented with preleukemia and loss of all or part of chromosome 7 were studied. Initial presentation, with cytopenias and less than 25% blasts in the bone marrow, was between 13 and 30 months of age. Progression to acute nonlymphocytic leukemia occurred 1-8 months after initial presentation. The morphologic type was megakaryoblastic in two, and undifferentiated in one. Two children achieved remission with intensive therapy, and one continues in remission off therapy; the other child died in remission of accidental causes. The third child died of respiratory distress and leukemia after no intervention was chosen. These cases represent the first examples of chromosome 7 abnormalities associated with DS and leukemia, and suggest differences from the "monosomy 7" syndrome seen in children without DS.     

Auditory evoked potentials in children and adolescents with Down syndrome

Down syndrome, or trisomy 21, is the most common genetic alteration in humans. The syndrome presents with several features, including hearing loss and changes in the central nervous system, which may affect language development in children and lead to school difficulties. The present study aimed to investigate group differences in the central auditory system by long‐latency auditory evoked potentials and cognitive potential. An assessment of 23 children and adolescents with Down syndrome was performed, and a control group composed of 43 children and adolescents without genetic and/or neurological changes was used for comparison. All children underwent evaluation with pure tone and vocal audiometry, acoustic immitance measures, long‐latency auditory evoked potentials, and cognitive potential. Longer latencies of the waves were found in the Down syndrome group than the control group, without significant differences in amplitude, suggesting that individuals with Down syndrome have difficulty in discrimination and auditory memory. It is, therefore, important to stimulate and monitor these children in order to enable adequate development and improve their life quality. We also emphasize the importance of the application of auditory evoked potentials in clinical practice, in order to contribute to the early diagnosis of hearing alterations and the development of more research in this area.     

Guidelines for the medical management of Irish children and adolescents with Down syndrome

Down syndrome (DS) is the most common chromosomal cause of developmental disability in Ireland. Children with DS have a high incidence of associated treatable medical disorders where early intervention carries a better outcome. Currently there are no agreed protocols for the screening and management of children and adults with DS in Ireland. A cross-sectional study of 394 children and adolescents was undertaken in the Eastern Regional Health Authority (ERHA) to assess the medical needs of children and adolescents with DS, in order to develop medical management guidelines. This study provides evidence-based data that children and adolescents with DS have a high incidence of treatable medical disorders, which supports the need for the medical management guidelines presented.     

Micronucleated lymphocytes in parents of Down syndrome children

Down syndrome (DS) is the most common disease due to an autosomal aneuploidy in live born children and also the major known genetic cause of mental retardation. The risk of a DS pregnancy increases substantially with increasing maternal age. However, several women aged less than 35 years at conception have a child with DS. The micronucleus (MN) assay can identify chromosome breakage or chromosome malsegregation and is an ideal biomarker to investigate genomic instability. The aim of the present study was to determine the frequency of peripheral lymphocytes with MN in the parents of DS individuals. The subjects were 17 couples, 1 father and 9 mothers, and 24 couples who had at least one healthy child formed the control group. For each individual we evaluated the frequency of binucleated micronucleated lymphocytes (BNMN%) as number of binucleated lymphocytes containing one or more MN per 1000 binucleated cells. The mean age of DS parents and controls was 32.6 and 29.8 years, respectively. The frequency of MN in DS parents was significantly higher compared to controls. The higher frequency of MN in DS parents suggests a higher predisposition of DS parents to aneuploidy events in this sample.     

An assessment of the vestibulo-ocular reflex (VOR) in persons with Down syndrome

Down syndrome (DS), the most common genetically defined cause of intellectual disability, is the phenotypic consequence of a supernumerary chromosome 21. Persons with DS commonly display deficits in visuomotor integration, motor coordination, and balance. Despite the key roles of the optokinetic and vestibular systems in these submodalities of motor function, a systematic investigation into the optokinetic nystagmus (OKN) and vestibulo-ocular reflex (VOR) in persons with DS was lacking in the literature. Accordingly, this study generated quantitative data on oculomotor function in persons with DS under vestibular stimulation (an accompanying work describes results on the analysis of optokinetic function in the same cohort of participants). Experiments involved 32 participants with DS (14–36 years old, equally divided by gender) and 32 chronological age- and gender-matched typically developing controls. Eye movements were recorded by binocular video-oculography, and a servo-controlled rotary chair produced vestibular stimulation. Participants were assessed for VOR during step, ramp, and sinusoidal stimulations; inhibition of the VOR by visual target fixation; and VOR adaptation to conflicting visual input. Individuals with DS displayed small alterations in the VOR gain and dynamics compared to controls. In contrast, the number of VOR nystagmus beats and the ability to inhibit the VOR by visual target fixation were markedly and robustly smaller in persons with DS. Significantly increased VOR adaptation was observed in men with DS. These findings may have implications to the understanding of the neurological basis of the motor dysfunction that affects performance in many practical tasks persons with DS encounter in their everyday lives.     

Altered immune parameters correlate with infection-related hospitalizations in children with Down syndrome

In addition to previously studied immunological variables, the relative expression of IFNGR2, IFNAR1, CD18, and CD275 (all encoded in chromosome 21) on circulating leucocytes and multifunctional T cells (evaluated by an intracellular cytokine/proliferation assay) were compared between children with Down syndrome (DS) and healthy controls (HC). As previously reported, numbers of lymphocytes, CD4⁺ T cells, Treg cells, B cells, and levels of serum IgM were decreased, and levels of IgG and IgA were increased in children with DS. Moreover, the relative expression of CD18 on T and B cells (previously and not previously reported, respectively) were elevated in DS children (p ⩽ 0.01). Age and numbers of B and Treg cells moderately correlated with retrospectively identified infection related hospitalizations (rho: 0.300–0.460, p ⩽ 0.003). Age and the numbers of Treg cells also correlated with prospectively identified infection related hospitalizations. Future studies are necessary to clarify the role of these parameters in the immunity of DS patients.