Health care transition for individuals with Down syndrome: A needs assessment.

Transition to adulthood is a multifaceted process that requires integration of numerous domains within a young person's life, including their health care. For children with special health care needs, the transition process can be markedly more difficult to navigate. This is especially true for children with Down syndrome (DS) who receive fewer transition planning services. The aim of this needs assessment was to identify current trends, potential gaps, and areas for targeted intervention within the current transition landscape for individuals with DS. We utilized DS-Connect, a National Institutes of Health (NIH) funded family/self-advocate survey repository, as a platform to recruit respondents to the "Transition to Adulthood" survey. Sixty-five respondents (64 parents and 1 caregiver) completed the survey. Responses indicated that 42% of respondents reported comfort in the transition process, but 5% or less reported completing one of the core transition outcomes: transition readiness assessment, portable medical summary, or written transition plan. These findings translated across other domains of respondents' lives. While many individuals with DS and their caregivers are aware of the transition process, there appears to be a disconnect between the introduction of transition concepts and an actualization of transition outcomes necessary for success.

Facial analysis technology for the detection of Down syndrome in the Democratic Republic of the Congo.

Down syndrome is one of the most common chromosomal anomalies affecting the world's population, with an estimated frequency of 1 in 700 live births. Despite its relatively high prevalence, diagnostic rates based on clinical features have remained under 70% for most of the developed world and even lower in countries with limited resources. While genetic and cytogenetic confirmation greatly increases the diagnostic rate, such resources are often non-existent in many low- and middle-income countries, particularly in Sub-Saharan Africa. To address the needs of countries with limited resources, the implementation of mobile, user-friendly and affordable technologies that aid in diagnosis would greatly increase the odds of success for a child born with a genetic condition. Given that the Democratic Republic of the Congo is estimated to have one of the highest rates of birth defects in the world, our team sought to determine if smartphone-based facial analysis technology could accurately detect Down syndrome in individuals of Congolese descent. Prior to technology training, we confirmed the presence of trisomy 21 using low-cost genomic applications that do not need advanced expertise to utilize and are available in many low-resourced countries. Our software technology trained on 132 Congolese subjects had a significantly improved performance (91.67% accuracy, 95.45% sensitivity, 87.88% specificity) when compared to previous technology trained on individuals who are not of Congolese origin (p < 5%). In addition, we provide the list of most discriminative facial features of Down syndrome and their ranges in the Congolese population. Collectively, our technology provides low-cost and accurate diagnosis of Down syndrome in the local population.

Assessment of radial glia in the frontal lobe of fetuses with Down syndrome.

Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in the frontal lobe of the developing human fetal brain with DS and age-matched controls. Secondly, we investigated whether microstructural information from in vivo magnetic resonance imaging (MRI) could reflect histological findings from human brain tissue samples. Immunohistochemistry was performed on paraffin-embedded human post-mortem brain tissue from nine fetuses and neonates with DS (15-39 gestational weeks (GW)) and nine euploid age-matched brains (18-39 GW). Radial glia markers CRYAB, HOPX, SOX2, GFAP and Vimentin were assessed in the Ventricular Zone, Subventricular Zone and Intermediate Zone. In vivo diffusion MRI was used to assess microstructure in these regions in one DS (21 GW) and one control (22 GW) fetal brain. We found a significant reduction in radial glial progenitor SOX2 and subtle deviations in radial glia expression (GFAP and Vimentin) prior to 24 GW in DS. In vivo, fetal MRI demonstrates underlying radial projections consistent with immunohistopathology. Radial glial alterations may contribute to the subsequent simplified gyral patterns and decreased cortical volumes observed in the DS brain. Recent advances in fetal MRI acquisition and analysis could provide non-invasive imaging-based biomarkers of early developmental deviations.

Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment.

Down Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify the development of the fetal and neonatal brain in DS participants, with and without a congenital cardiac defect compared with a control population using dedicated, optimised and motion-corrected in vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks' gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, we believe that the results of this study will assist counselling for prospective parents.

Assessment of genomic instability and proliferation index in cultured lymphocytes of patients with Down syndrome, congenital anomalies and aplastic anaemia.

One hundred and fifteen cases [Down Syndrome (DS) n = 75, Multiple Congenital Anomalies (MCA) n = 15 and Aplastic Anaemia (AA) n = 25], with respect to their nature of predisposition to cancer, were selected for clinical, cytogenetic and cyto-molecular studies to understand the severity of genomic instability according to the nature of the different diseases. Cytogenetic studies included chromosomal aberration (CA) assays and cytokinesis block micronucleus cytome (CBMN-Cyt) assays. In DS, MCA and AA, average frequencies of nuclear anomalies (NA) were 0.015 ±â€¯0.0006, 0.021 ±â€¯0.00123, 0.031 ±â€¯0.00098, respectively and CA were 0.107 ±â€¯0.003, 0.105 ±â€¯0.008, 0.158 ±â€¯0.006, respectively per metaphase. The extent of genomic instability in patients analysed by CBMN-Cyt assays and CA assays was statistically significant in all groups. Comparatively decreased cytokinesis block proliferation index (CBPI) observed in AA patients of 1.59 ±â€¯0.05, support the assumption that decreased levels of CBPI indicate increased genomic damage. Furthermore, we performed peptide nucleic acid fluorescence in situ hybridisation (PNA FISH) analysis to understand the mechanisms behind genomic instability and telomere dysfunction. PNA FISH showed increased frequencies of telomere signal free ends (0.98 ±â€¯0.13) in individuals with higher genomic instability. Therefore, the results demonstrate that increased chromosomal instability along with higher telomere attrition or loss may initiate gross DNA damage and leads to chromosomal instability, which is an important mechanism for triggering genomic instability - an important hallmark of cancer cells.

New radiological parameters for the assessment of atlantoaxial instability in children with Down syndrome: the normal values and the risk of spinal cord injury.

AIMS: To determine the normal values and usefulness of the C1/4 space available for spinal cord (SAC) ratio and C1 inclination angle, which are new radiological parameters for assessing atlantoaxial instability in children with Down syndrome. PATIENTS AND METHODS: We recruited 272 children with Down syndrome (including 14 who underwent surgical treatment), and 141 children in the control group. All were aged between two and 11 years. The C1/4 SAC ratio, C1 inclination angle, atlas-dens interval (ADI), and SAC were measured in those with Down syndrome, and the C1/4 SAC ratio and C1 inclination angle were measured in the control group. RESULTS: The mean C1/4 SAC ratio in those requiring surgery with Down syndrome, those with Down syndrome not requiring surgery and controls were 0.63 (standard deviation (sd) 0.1), 1.15 (sd 0.13) and 1.29 (sd 0.14), respectively, and the mean C1 inclination angles were -3.1° (sd 10.7°), 15.8° (sd 7.3) and 17.2° (sd 7.3), in these three groups, respectively. The mean ADI and SAC in those with Down syndrome requiring surgery and those with Down syndrome not requiring surgery were 9.8 mm (sd 2.8) and 4.3 mm (sd 1.0), and 11.1 mm (sd 2.6) and 18.5 mm (sd 2.4), respectively. CONCLUSION: The normal values of the C1/4 SAC ratio and the C1 inclination angle were found to be about 1.2° and 15º, respectively. Cite this article: Bone Joint J 2016;98-B:1704-10.

Hospitalizations and associated costs in a population-based study of children with Down syndrome born in Florida.

BACKGROUND: Our objective was to examine differences in hospital resource usage for children with Down syndrome by age and the presence of other birth defects, particularly severe and nonsevere congenital heart defects (CHDs). METHODS: This was a retrospective, population-based, statewide study of children with Down syndrome born 1998 to 2007, identified by the Florida Birth Defects Registry (FBDR) and linked to hospital discharge records for 1 to 10 years after birth. To evaluate hospital resource usage, descriptive statistics on number of hospitalized days and hospital costs were calculated. Results were stratified by isolated Down syndrome (no other coded major birth defect); presence of severe and nonsevere CHDs; and presence of major FBDR-eligible birth defects without CHDs. RESULTS: For 2552 children with Down syndrome, there were 6856 inpatient admissions, of which 68.9% occurred during the first year of life (infancy). Of the 2552 children, 31.7% (n = 808) had isolated Down syndrome, 24.0% (n = 612) had severe CHDs, 36.3% (n = 927) had nonsevere CHDs, and 8.0% (n = 205) had a major FBDR-eligible birth defect in the absence of CHD. Infants in all three nonisolated DS groups had significantly higher hospital costs compared with those with isolated Down syndrome. From infancy through age 4, children with severe CHDs had the highest inpatient costs compared with children in the other sub-groups. CONCLUSION: Results support findings that for children with Down syndrome the presence of other anomalies influences hospital use and costs, and children with severe CHDs have greater hospital resource usage than children with other CHDs or major birth defects without CHDs.

Human and mouse model cognitive phenotypes in Down syndrome: implications for assessment.

The study of cognitive function in Down syndrome (DS) has advanced rapidly in the past decade. Mouse models have generated data regarding the neurological basis for the specific cognitive profile of DS (i.e., deficits in aspects of hippocampal, prefrontal, and cerebellar function) and have uncovered pharmacological treatments with the potential to affect this phenotype. Given this progress, the field is at a juncture in which we require assessments that may effectively translate the findings acquired in mouse models to humans with DS. In this chapter, we describe the cognitive profile of humans with DS and associated mouse models, discussing the ways in which we may merge these findings so as to more fully understand cognitive strengths and weaknesses in this population. New directions for approaches to cognitive assessment in mice and humans are discussed.

Peripheral vestibular system in Down syndrome: quantitative assessment of vestibular histopathology.

OBJECTIVE: To evaluate the maturity of the peripheral vestibular system in Down syndrome by examining the number of Scarpa's ganglion cells and the density of vestibular hair cells. STUDY DESIGN: Case-control study using human temporal bones. SETTING: Tertiary academic center, otopathology laboratory. SUBJECTS AND METHODS: Sixteen temporal bones from 8 patients with Down syndrome and 15 control temporal bones from 8 individuals with no history of otologic disease were selected. Hypoplasia of the lateral semicircular canal (LSC) and vestibule was investigated by measuring the dimensions of the structures. Scarpa's ganglion cells were counted under light microscopy. The vestibular hair cells were counted in the LSC crista and the utricular and saccular maculae under differential interference contrast (Nomarski) microscopy and expressed as density. RESULTS: The patients with Down syndrome were divided into 2 groups: with and without LSC hypoplasia. The number of Scarpa's ganglion cells and the density of vestibular hair cells were significantly smaller in both groups of patients with Down syndrome than in the control group. There was no significant difference in the number of Scarpa's ganglion cells or the density of vestibular hair cells between the groups with and without LSC hypoplasia. CONCLUSION: The peripheral vestibular system, including Scarpa's ganglion cells and vestibular hair cells, is hypoplastic irrespective of the vestibular malformation in Down syndrome.

Three-dimensional assessment of nose and lip morphology in North Sudanese subjects with Down syndrome.

OBJECTIVE: To detail the nasolabial morphologic characteristics of North Sudanese subjects with Down syndrome (DS). MATERIALS AND METHODS: Nasolabial morphology was assessed three-dimensionally in 64 North Sudanese subjects with DS aged 4 to 34 years and in 682 sex- and age-matched controls. Three-dimensional facial coordinates were collected using a laser scan, and selected distances, angles, areas, and volumes were computed. Subject and reference data were compared by computing z-scores and Student's t-tests. RESULTS: The nose was significantly smaller (area) in subjects with DS than in reference subjects, and it had a different shape (more flat angle of alar slope, more acute nasal tip angle). The vertical (nasal bridge length, nose height) and anteroposterior (nasal tip protrusion) dimensions were reduced, while the horizontal dimensions (alar base width, inferior widths of the nostrils) were increased. The nasolabial angle was increased. The cutaneous lip volume was significantly smaller, while the vermilion lip area was larger in the subjects with DS. The mouth and philtrum widths were significantly reduced, while the vermilion height was significantly increased. CONCLUSION: Analyzed subjects with DS had a hypoplastic nose and different upper and lower lips than did reference, normal subjects.

A construção da identidade e a relação com o outro. Abertura oficial e Conferência: O que é ser deficiente

Contém vídeo com a abertura oficial do Fórum, palestra com Sergio Gerardo García da cidade de Monterrey- México falando sobre o que é ser deficiente. O DVD também apresenta imagens da Exposição de Artes de trabalhos realizados por pessoas portadoras de deficiência

A construção da identidade e a relação com o outro. Políticas Públicas de Direitos da Pessoa com Deficiência

Apresenta duas palestras sobre Políticas Públicas para Pessoas com Deficiência, dos palestrantes Gastão Wagner de Souza Campos - professor titular de Medicina Preventiva da UNICAMP e Raquel Elias Ferreira Dodge - Sub-Procuradora Geral da República de Direitos da Cidadania da Procuradoria Geral da República - Brasília-DF. As palestras abordam os direitos das pessoas com deficiência e as iniciativas do Governo em oferecer-lhes meios de inclusão social e cidadania

Morphometry of the ear in Down's syndrome subjects. A three-dimensional computerized assessment.

The three-dimensional coordinates of 13 soft-tissue landmarks on the ears were obtained by a computerized digitizer in 28 subjects with Down's syndrome aged 12-45 years, and in 449 sex, age and ethnic group matched controls. From the landmarks, left and right linear distances (ear width and length), ratios (ear width-to-ear length), areas (ear area), angles (angle of the auricle versus the facial midplane) and the three-dimensional symmetry index were calculated. For both males and females, all linear dimensions and areas were significantly (Analysis of Variance, P < 0.001) larger in the reference subjects than in the subjects with Down's syndrome. All values significantly increased as a function of age (P < 0.05); the increment was larger in the reference subjects than in the subjects with Down's syndrome. On both sides of the face, the subjects with Down's syndrome had larger ear width-to-ear length ratios, and larger angles of the auricle versus the facial midplane than the reference subjects. The three-dimensional symmetry index was significantly larger in the reference subjects and in the older persons. In conclusion, ear dimensions, position and shape significantly differed in subjects with Down's syndrome when compared to sex, age and ethnic group matched controls. Some of the differences were sex and age related.

A quantitative three-dimensional assessment of abnormal variations in the facial soft tissues of individuals with Down syndrome.

OBJECTIVE: To supply quantitative information about the facial soft tissues of subjects with Down syndrome by using summary anthropometric measurements. DESIGN, SETTING, AND PATIENTS: The three-dimensional coordinates of soft tissue facial landmarks were obtained using a computerized digitizer in 28 subjects with Down syndrome (11 girls and women and 17 boys and men aged 12 to 45 years) and 429 healthy controls matched for sex, age, and ethnicity. From the landmarks, 18 facial dimensions were calculated. Data were compared with those collected in healthy individuals by computing z-scores. Two summary anthropometric measurements for quantifying craniofacial variations were assessed in both the subjects with Down syndrome and the reference subjects: the mean z-score (an index of overall facial size) and its standard deviation, craniofacial variability index (an index of facial harmony). RESULTS: In subjects with Down syndrome, facial size was smaller than in normal individuals, and in 17 subjects the mean z-score fell outside the normal interval (mean +/- 2 SD). Twenty subjects had a craniofacial variability index larger than the normal interval. CONCLUSIONS: The facial soft tissue structures of subjects with Down syndrome differed from those of normal controls of the same age, sex, and ethnic group: a reduced facial size was coupled with a global anomalous relationship between individual measurements. The two indices allowed discriminating more than 89% of subjects with Down syndrome when compared with normal subjects.

Three-dimensional assessment of nose and lip morphology in subjects with down syndrome.

Nasolabial morphology was assessed 3-dimensionally in 28 subjects with Down syndrome aged 12-45 years and in 449 sex- and age-matched controls. Subject and reference data were compared by computing z scores and calculating Student's t tests. The nose was significantly smaller (volume, area) in the subjects with Down syndrome than in the reference subjects, and it had a different shape (more flat angle of alar slope, more acute nasal tip angle). The vertical (length of the nasal bridge, height of the nose) and anteroposterior (nasal tip protrusion) dimensions were reduced, while the horizontal dimensions (alar base width, superior and inferior widths of the nostrils) were increased. The lower lip was significantly smaller (volume, area, vermilion height), while the upper lip was larger (area, vermilion height) in the subjects with Down syndrome. The mouth width was also significantly smaller. In conclusion, the analyzed subjects with Down syndrome had a hypoplastic nose and different upper and lower lips than reference, normal subjects.

Intra- and interoperator variability in fetal nasal bone assessment at 11-14 weeks of gestation.

OBJECTIVES: Examination of the fetal nasal bones by ultrasound between 11 and 14 weeks of gestation has been proposed as an additional tool in the detection of trisomy 21 in a high-risk population. However the variability in the identification of fetal nasal bones by ultrasound has not yet been investigated. The aim of this study was to assess the intraobserver and interobserver reproducibility of fetal nasal bone identification by ultrasound between 11 and 14 weeks of gestation. METHODS: A total of 1040 consecutive ultrasound examinations were performed at 11-14 weeks of gestation for nuchal translucency (NT) measurement and nasal bone identification by ultrasound. A total of 657 consecutive video-loops were assessed by three experienced operators. Each operator assigned cases to one of three categories, namely present, uncertain or absent nasal bones, and the results were compared between operators. To assess the intraoperator variability each operator reviewed 100 randomly selected videos out of the 657 loops and again used the same classification. Results were compared by pairwise unweighted and weighted Kappa index to evaluate the inter- and intraoperator variability. RESULTS: Among the 1040 fetuses, there were 51 (4.9%) with an NT measurement above the 95th centile. Nasal bones were identified by ultrasound in 948, not seen in eight and impossible to assess in 84 fetuses. Four fetuses had trisomy 21 including three with absent nasal bones and increased NT and one with present nasal bones and normal NT. The Kappa and weighted Kappa values for interoperator variability between the three operators were between 0.26 and 0.37 and 0.33 and 0.44, respectively. The Kappa and weighted Kappa values for intraoperator variability were between 0.35 and 0.48 and 0.43 and 0.55, respectively. CONCLUSION: The assessment of fetal nasal bones is only fairly reproducible. Although the performance of the test in fetuses at high risk for trisomy 21 has been reported to be good, its implementation as an additional screening technique in the general population must be accompanied by teaching and quality control programs.

Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL.

We have previously shown that Alzheimer disease (AD) brain exhibits terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) for DNA damage and morphological evidence for apoptosis. Down syndrome (DS) is a neurodegenerative disorder that exhibits significant neuropathological parallels with AD. In accordance with these parallels and the need to clarify the mechanism of cell death in DS and AD, we investigated two principal issues in the present study. First, we investigated the hypothesis that TUNEL labeling for DNA damage and morphological evidence for apoptosis is also present in the DS brain. All DS cases employed had a neuropathological diagnosis of AD. Analysis of these cases showed that DS brain exhibits a significant increase in the number of TUNEL-labeled nuclei relative to controls matched for age, Postmortem Delay, and Archival Length, and that a subset of TUNEL-positive nuclei exhibits apoptotic morphologies. We also report that Archival Length in 10% formalin can significantly affect TUNEL labeling in postmortem human brain, and therefore, that Archival Length must be controlled for as a variable in this type of study. Second, we investigated whether biochemical evidence for the mechanism of cell death in DS and AD could be detected. To address this question we employed pulsed-field gel electrophoresis (PFGE) as a sensitive method to evaluate DNA integrity. Although apoptotic oligonucleosomal laddering has not previously been observed in AD, PFGE of DNA from control, DS and AD brain in the present study revealed evidence of high molecular weight DNA fragmentation indicative of apoptosis. This represents biochemical support for an apoptotic mechanism of cell death in DS and AD.

[Assessment of the brainstem and the cerebellar lesions and myelination using magnetic resonance images in children with Down syndrome].

Magnetic resonance images were carried out in the children with Down syndrome aged 2-4 years old compared with the values of the age-matched controls. The pons and cerebellar vermis were significantly smaller and the cerebral peduncles were narrower in Down syndrome. None of the patients showed delay of myelination. These findings suggest hypoplasia of the pons and cerebellum in Down syndrome.

Autosomal-recessive omodysplasia: prenatal diagnosis and histomorphometric assessment of the physeal plates of the long bones.

Second-semester ultrasonography of a female fetus documented short femora and humeri and dislocation of the radii. Based on the clinical and postmortem radiological findings, autosomal-recessive omodysplasia was diagnosed. The physeal plates of the long tubular bones were assessed by computer-assisted image analysis. The dimensions and orientation of the chondrocytic lacunae in the physeal plates of the omodysplastic fetus were compared with those in the physeal plates of fetuses without gross limb abnormalities (oligohydramnios, n = 2; hydrocephalus, n = 2; Down syndrome, n = 1). The pathological characteristics of the omodysplastic physeal plates were an expanded zone of proliferating cartilage and an increased number of closely packed, small chondrocytes. We propose that a genetic, functional deficiency of the physeal cells, underlying the short-limbed dwarfism of autosomal-recessive omodysplasia, is partially compensated, albeit ineffectively, by an increased number of small chondrocytes in the proliferating zone of the physeal plate.