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Effect of antibiotics in preventing hospitalizations from respiratory tract infections in children with Down syndrome.
Manikam, L, Lakhanpaul, M, Schilder, AGM, Littlejohns, P, Cupp, MA, Alexander, EC, Hayward, A
Pediatric pulmonology. 2021;(1):171-178
Abstract
BACKGROUND Children with Down syndrome (DS) are at high risk of respiratory tract infections (RTIs) due to anatomical variations, comorbidities, and immune system immaturity. Evidence on interventions to reduce this risk is incomplete. This study aims to quantify the effect of antibiotics prescribed for RTIs in primary care on the subsequent risk of RTI-related hospitalization for children with DS versus controls. METHODS We conducted a retrospective cohort study of 992 children with DS and 4874 controls managed by UK National Health Service General Practitioners (GPs) and hospitals as identified in CALIBER (Clinical disease research using LInked Bespoke studies and Electronic health Records), 1997-2010. Univariate and multivariate logistic regression were undertaken. RESULTS In children with DS, the prescription of antibiotics following an RTI-related GP consultation did not significantly reduce the risk of RTI-related hospitalization in the subsequent 28 days (risk with antibiotics, 1.8%; without, 2.5%; risk ratio, 0.699; 95% confidence interval, 0.471-1.036). Subgroup analyses showed a risk reduction only in infants with DS, after adjustment for covariates. There was no reduction in risk for controls, overall or across subgroups. CONCLUSIONS In conclusion, while prescription of antibiotics following RTI-related GP consultations were effective for infants with DS in reducing subsequent RTI-related hospitalization, this was not the case for older children with DS. We would encourage further high-quality cohort and randomized controlled trials to interrogate this finding, and to examine the impact of antibiotics on other endpoints, including symptom duration.
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[Consensus of the Genetics Branch of the Chilean Society of Pediatrics on the prioritization of people with Down syndrome and rare diseases for vaccination against SARS-CoV-2].
Faundes, V, Pardo, R, Cammarata-Scalisi, F, Alarcon, P, Lay-Son, G, San Martin, E
Andes pediatrica : revista Chilena de pediatria. 2021;(2):309-315
Abstract
In the framework of the vaccination campaign against the SARS-CoV-2 virus, the Chilean Ministry of Health requested advice from the Genetics Branch of the Chilean Society of Pediatrics, to define the level of prioritization for people with Down Syndrome . A panel of geneticists worked on the development of this consensus, in which not only patients with Down syndrome were included, but the search was extended to patients with other types of disabilities, in both pediatric and adult ages in or der to contribute to the development of public health measures against the COVID-19 pandemic. The consensus concludes that, given the prevalence of comorbidities associated with Down syndrome, the higher incidence of cases with severe COVID-19 in this population group and a higher mortality, individuals with trisomy 21 should be considered as a high-risk population, and therefore, vaccina tion against SARS-CoV-2 should have a high priority for all people with Down syndrome regardless of their age (except for the age limit established by the clinical trials of each vaccine), and should be preceded only by the groups of health personnel and adults aged > 60-65 years. Likewise, this group of experts urges health authorities to include people with intellectual disabilities and related conditions as a priority population (other chromosomal abnormalities other than Down syndrome, intellectual disability, congenital anomalies and conditions that cause disability with microcephaly), as well as the caregivers of people with this type of conditions. Vaccination in children with this type of disorders should be considered as part of the first priority group, once safe vaccines against SARS-CoV-2 are available for use in children and adolescents.
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Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial.
Malan, V, Bussières, L, Winer, N, Jais, JP, Baptiste, A, Le Lorc'h, M, Elie, C, O'Gorman, N, Fries, N, Houfflin-Debarge, V, et al
JAMA. 2018;(6):557-565
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Abstract
IMPORTANCE Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancies at a high risk of trisomy 21 to decrease the number of required invasive fetal karyotyping procedures and their associated miscarriages. The effect of this strategy has not been evaluated. OBJECTIVE To compare the rates of miscarriage following invasive procedures only in the case of positive cfDNA test results vs immediate invasive testing procedures (amniocentesis or chorionic villus sampling) in women with pregnancies at high risk of trisomy 21 as identified by first-trimester combined screening. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted from April 8, 2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first-trimester screening. INTERVENTIONS Patients were randomized to receive either cfDNA testing followed by invasive testing procedures only when cfDNA tests results were positive (n = 1034) or to receive immediate invasive testing procedures (n = 1017). The cfDNA testing was performed using an in-house validated method based on next-generation sequencing. MAIN OUTCOMES AND MEASURES The primary outcome was number of miscarriages before 24 weeks' gestation. Secondary outcomes included cfDNA testing detection rate for trisomy 21. The primary outcome underwent 1-sided testing; secondary outcomes underwent 2-sided testing. RESULTS Among 2051 women who were randomized and analyzed (mean age, 36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial. The miscarriage rate was not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk difference of -0.03% (1-sided 95% CI, -0.68% to ∞; P = .47). The cfDNA detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%). CONCLUSIONS AND RELEVANCE Among women with pregnancies at high risk of trisomy 21, offering cfDNA screening, followed by invasive testing if cfDNA test results were positive, compared with invasive testing procedures alone, did not result in a significant reduction in miscarriage before 24 weeks. The study may have been underpowered to detect clinically important differences in miscarriage rates. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02127515.
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Clinical management of childhood hyperthyroidism with and without Down syndrome: a longitudinal study at a single center.
Dos Santos, TJ, Martos-Moreno, GÁ, Muñoz-Calvo, MT, Pozo, J, Rodríguez-Artalejo, F, Argente, J
Journal of pediatric endocrinology & metabolism : JPEM. 2018;(7):743-750
Abstract
Background The approach to the clinical management of Graves' disease (GD) is debatable. This study aimed to identify predictors of remission in pediatric GD. Methods A longitudinal study of 36 children and adolescents with GD followed from 1997 to 2017 at a single tertiary hospital was performed. Clinical and biochemical parameters, including comorbidities, treatment with anti-thyroid drugs (ATD) or definitive therapy (radioiodine [RIT] and thyroidectomy), and remission as the main outcome were collected. We performed a multivariable logistic regression analysis to identify likely predictors of remission. Results Among patients, most were female, in late puberty, with exuberant symptoms at onset. Eleven also suffered from Down syndrome (DS). Thirty-four patients (94%) started on methimazole from disease onset, and 25 (69%) received it as the only therapy, with a mean duration of 2.7±1.8 years. Six changed to RIT and three underwent thyroidectomy; no DS patient received definitive therapy. Remission was higher in DS patients (45% vs. 25%, p=0.24), but afterwards (3.9±2.5 vs. 2.3±1.4 years, p<0.05); there was no significance in relapsing (20% vs. 15%). Females were less likely to reach remission (p<0.05); serum free thyroxine at onset was higher (p<0.05) in patients who required definitive therapy. Thyroid-stimulating immunoglobulin (TSI) values normalized in exclusively ATD therapy, especially from 2 years on (p<0.05). Conclusions Males were more likely to achieve remission. TSI values may normalize in GD, notably from the second year of treatment. DS children may benefit with conservative management in GD.
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Influence of complex childhood diseases on variation in growth and skeletal development.
Zemel, BS
American journal of human biology : the official journal of the Human Biology Council. 2017;(2)
Abstract
The study of human growth and skeletal development by human biologists is framed by the larger theoretical concerns regarding the underpinnings of population variation and human evolution. This unique perspective is directly relevant to the assessment of child health and well-being at the individual and group level, as well as the construction of growth charts. Environmental, behavioral (nutrition and physical activity), and disease-related factors can prevent attainment of full genetic potential for growth. Undernutrition is most often the cause of growth faltering and poor skeletal development. Disease related factors, such as malabsorption, inflammation, and immobility also have profound effects. These effects will be illustrated with examples from diseases such as cystic fibrosis, inflammatory bowel disease, and Down syndrome. The need for separate growth charts for children with genetic disorders is often controversial because of potential medical and/or nutritional complications associated with some disorders. Children with Alagille syndrome and Down syndrome will be used to illustrate the advantages and limitations of syndrome-specific charts. This overview of health and disease effects on growth and skeletal development provides insights into the plasticity of human growth and its sensitivity to overall health and well-being.
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Down's Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship.
Dey, N, Krie, A, Klein, J, Williams, K, McMillan, A, Elsey, R, Sun, Y, Williams, C, De, P, Leyland-Jones, B
International journal of molecular sciences. 2017;(6)
Abstract
Down's syndrome (DS), the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21). Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H., The Lancet Oncology, 2001). A study conducted in the United States found only one death when 11.65 were expected (Scholl T et al., Dev Med Child Neurol. 1982). A recent study examined mammogram reports of women with DS treated in the largest medical facility specifically serving adults with DS in the United States. It was found that only 0.7% women with DS had been diagnosed with breast cancers (Chicoine B et al., Intellect Dev Disabil. 2015). Here we describe a case of breast cancer in a 25-year-old patient with DS. The disease was presented as lymph node positive carcinoma with alterations of tumor suppressor genes characteristic to the triple negative breast cancer subtype. Comprehensive Genomic Profiling (CGP) revealed a wild-type status for BRCA1. The CGP report showed a frameshift mutation, A359fs*10 of the tumor suppressor gene INPP4B and another frameshift mutation, R282fs*63 of tumor suppressor gene TP53 in the tumor biopsy as characteristically found in triple-negative breast cancers. The VUS (Variance of Unknown Significance) alteration(s) were identified in ASXL1 (L1395V), NTRK1 (G18E), DDR2 (I159T), RUNX1 (amplification), ERG (amplification), SOX2 (T26A), FAM123B (G1031D), and HNF1A (A301T). Bonafide cancer-related genes of chromosome 21 amplified in the patient's tumor are RUNX1 and ERG genes. After the completion of the radiation, the patient was placed on everolimus which was based on the result of her CGP report. Thus, post-mastectomy radiation therapy was completed with a recommendation for everolimus for one year. During the time of writing of this report, no metastatic lesions were identified. The patient currently has no evidence of disease.
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Anomalous White Matter Structure and the Effect of Age in Down Syndrome Patients.
Fenoll, R, Pujol, J, Esteba-Castillo, S, de Sola, S, Ribas-Vidal, N, García-Alba, J, Sánchez-Benavides, G, Martínez-Vilavella, G, Deus, J, Dierssen, M, et al
Journal of Alzheimer's disease : JAD. 2017;(1):61-70
Abstract
BACKGROUND Neural tissue alterations in Down syndrome are fully expressed at relatively late developmental stages. In addition, there is an early presence of neurodegenerative changes in the late life stages. OBJECTIVE The aims of this study were both to characterize white matter abnormalities in the brain of adult Down syndrome patients using diffusion tensor imaging (DTI) and to investigate whether degenerative alterations in white matter structure are detectable before dementia is clinically evident. METHODS Forty-five adult non-demented Down syndrome patients showing a wide age range (18-52 years) and a matched 45-subject control group were assessed. DTI fractional anisotropy (FA) brain maps were generated and selected cognitive tests were administered. RESULTS Compared with healthy controls, non-demented Down syndrome patients showed lower DTI FA in white matter involving the major pathways, but with more severe alterations in the frontal-subcortical circuits. White matter FA decreased with age at a similar rate in both DS and control groups. CONCLUSIONS Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia.
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Caregiver-Reported Quality of Life in Youth with Down Syndrome.
Xanthopoulos, MS, Walega, R, Xiao, R, Prasad, D, Pipan, MM, Zemel, BS, Berkowitz, RI, Magge, SN, Kelly, A
The Journal of pediatrics. 2017;:98-104.e1
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Abstract
OBJECTIVES To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL. STUDY DESIGN Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index. Obesity was defined as a body mass index ≥95th percentile for age and sex. RESULTS Caregiver-reported Total QOL, Physical Health, and Psychosocial Health summary scores were all lower in the DS group compared with the non-DS controls (P < .001). Social and School Functioning were also lower (P < .001), but Emotional Functioning did not differ between DS and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P = .03) differed between youth without DS with and without obesity, but no differences were reported between youth with DS with and without obesity. On the Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers of non-DS youth. Caregivers of youth with obesity, regardless of DS status, reported significantly lower weight-specific QOL scores than caregivers of youth without obesity. CONCLUSION Caregivers reported lower QOL in youth with DS compared with youth without DS with the exception of emotional functioning. Obesity influences most domains of weight-related QOL in youth with and without DS; therefore, providers should address weight concerns in youth with obesity even in the presence of DS. CLINICAL TRIAL REGISTRATION NCT01821300.
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Craniospinal Germinomas in Patient with Down Syndrome Successfully Treated with Standard-Dose Chemotherapy and Craniospinal Irradiation: Case Report and Literature Review.
Miyake, Y, Adachi, JI, Suzuki, T, Mishima, K, Sasaki, A, Nishikawa, R
World neurosurgery. 2017;:995.e9-995.e15
Abstract
BACKGROUND Patients with Down syndrome (DS) are more likely to develop chemotherapy-related complications. The standard treatment for these patients with cancer has not yet been established, and the risks of standard chemotherapy are unclear. In this paper, a rare case of multiple craniospinal germinomas in a patient with DS, which was successfully treated with standard-dose chemotherapy combined with craniospinal irradiation, is reported. CASE DESCRIPTION The authors report a case of multiple craniospinal germinomas in a DS patient who presented with bilateral oculomotor and facial nerve palsy and hearing loss. The patient underwent 3 courses of combination chemotherapy using a standard dose of carboplatin and etoposide and 23.4 Gy of concurrent craniospinal irradiation. Posttreatment magnetic resonance imaging showed reduction of the tumors. Both fluorodeoxyglucose- and methionine-positron emission tomography demonstrated no uptake in the residual tumors. Follow-up magnetic resonance imaging and positron emission tomography did not reveal tumor recurrence for 18 months. CONCLUSIONS As far as we know, this is the first case of multiple craniospinal germinomas in a patient with DS who achieved a successful treatment result without fatal adverse events. The literature review indicated that disseminated germinomas may need intensive treatment to reduce recurrence risk. However, intensive chemotherapy using a combination of 3 or more anticancer drugs can increase the rate of treatment-related death during the early stage. Our case indicated that multiple craniospinal germinoma of DS patients could be treated with a standard dose of carboplatin and etoposide regimen with concurrent craniospinal irradiation along with appropriate supportive therapy and careful observation.
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Systematic review and meta-analysis shows a specific micronutrient profile in people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red blood cell copper and zinc, and higher salivary calcium and sodium.
Saghazadeh, A, Mahmoudi, M, Dehghani Ashkezari, A, Oliaie Rezaie, N, Rezaei, N
PloS one. 2017;(4):e0175437
Abstract
Different metabolic profiles as well as comorbidities are common in people with Down Syndrome (DS). Therefore it is relevant to know whether micronutrient levels in people with DS are also different. This systematic review was designed to review the literature on micronutrient levels in people with DS compared to age and sex-matched controls without DS. We identified sixty nine studies from January 1967 to April 2016 through main electronic medical databases PubMed, Scopus, and Web of knowledge. We carried out meta-analysis of the data on four essential trace elements (Cu, Fe, Se, and Zn), six minerals (Ca, Cl, K, Mg, Na, and P), and five vitamins (vitamin A, B9, B12, D, and E). People with DS showed lower blood levels of Ca (standard mean difference (SMD) = -0.63; 95% confidence interval (CI): -1.16 to -0.09), Se (SMD = -0.99; 95% CI: -1.55 to -0.43), and Zn (SMD = -1.30; 95% CI: -1.75 to -0.84), while red cell levels of Zn (SMD = 1.88; 95% CI: 0.48 to 3.28) and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57) were higher. They had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33) and Na (SMD = 1.04; 95% CI: 0.39 to 1.69). Our findings that micronutrient levels are different in people with DS raise the question whether these differences are related to the different metabolic profiles, the common comorbidities or merely reflect DS.