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Statement of problem Whether oral rehabilitation with dental implants in patients with Down syndrome leads to an increased complication rate is unclear. Purpose The purpose of this systematic review was to determine the effectiveness of dental implants placed in patients with Down syndrome and whether the condition is a risk factor or contraindication for dental implant placement. Material and methods Searches were conducted in 6 databases, including the non–peer-reviewed literature, up to February 2021 by 2 independent reviewers according to established inclusion and exclusion criteria to answer this question: Is Down syndrome a risk factor or contraindication for oral rehabilitation with dental implants? Results A total of 655 studies were initially found in the databases. Five were included in this systematic review, all of which were observational studies. A total of 50 patients with 186 implants were evaluated, with a reported effectiveness of 79.1%. The risk of bias assessment determined that 3 of the 5 studies had a high risk of bias. Conclusions Treatment with dental implants in patients with Down syndrome is a suitable option, but more complications are to be expected than with patients without this condition. Controlled studies with better methodological design and less risk of bias should be developed to improve the scientific evidence for the treatment of these patients.

Mucormycosis represents several unusual opportunistic infection caused by saprophytic aseptate fungi. There is a recent rise in cases of mucormycosis due to an increase in diabetic and immunodeficient patients like patients on long-term steroids, immunomodulators due to organ transplantation, malignancies, mainly haematological malignancies, and autoimmunity. Anatomically, mucormycosis can be localised most commonly as rhino-orbito-cerebral followed by pulmonary, disseminated, cutaneous and gastrointestinal, rarest being small intestinal. Patients with Down syndrome are immunodeficient due to their impaired immune response. Disseminated tuberculosis is also common in immunodeficient patients. We report a rare case of small intestinal mucormycosis in a patient with Down syndrome with coexisting intestinal tuberculosis. Due to the invasiveness of mucormycosis, the patient succumbed to death despite providing aggressive surgical debridement and medical management.

Due to the favorable test characteristics of the non-invasive prenatal test (NIPT) in the screening of fetal aneuploidy, there has been a strong and growing demand for implementation. In the Netherlands, NIPT is offered within a governmentally supported screening program as a first-tier screening test for all pregnant women (TRIDENT-2 study). However, concerns have been raised that the test’s favorable characteristics might lead to uncritical use, also referred to as routinization. This study addresses women’s perspectives on prenatal screening with NIPT by evaluating three aspects related to routinization: informed choice, freedom to choose and (personal and societal) perspectives on Down syndrome. Nationwide, a questionnaire was completed by 751 pregnant women after receiving counseling for prenatal screening. Of the respondents, the majority (75.5%) made an informed choice for prenatal screening as measured by the multidimensional measure of informed choice (MMIC). Education level and religious affiliation were significant predictors of informed choice. The main reason to accept screening was “seeking reassurance” (25.5%), and the main reason to decline was “every child is welcome” (30.6%). The majority of respondents (87.7%) did not perceive societal pressure to test. Differences between test-acceptors and test-decliners in personal and societal perspectives on Down syndrome were found. Our study revealed high rates of informed decision-making and perceived freedom to choose regarding fetal aneuploidy screening, suggesting that there is little reason for concern about routinization of NIPT based on the perspectives of Dutch pregnant women. Our findings highlight the importance of responsible implementation of NIPT within a national screening program.

Family history of thyroid disease (FHTD) constitutes a possible risk factor for congenital hypothyroidism (CH) in the general population; however, FHTD possible relationship with CH in subjects with Down syndrome (DS) has not yet been explored.To determine whether FHTD is associated with an increased incidence of CH in neonates with DS.Hospital-based case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and positive FHTD (cases) were compared with those of 183 newborns with DS without FHTD (control group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated.Nine newborns with DS in our sample had CH (4.1 %). In the multivariate analysis, FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8).Newborns with DS and FHTD have an eight-fold higher risk for CH, particularly when the index case is male. FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada.Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD.Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %).Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8).La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Individuals with Down syndrome are at increased risk of myeloid leukemia in early childhood, which is associated with acquisition of GATA1 mutations that generate a short GATA1 isoform called GATA1s. Germline GATA1s-generating mutations result in congenital anemia in males. We report on 2 unrelated families that harbor germline GATA1s-generating mutations in which several members developed acute megakaryoblastic leukemia in early childhood. All evaluable leukemias had acquired trisomy 21 or tetrasomy 21. The leukemia characteristics overlapped with those of myeloid leukemia associated with Down syndrome, including age of onset at younger than 4 years, unique immunophenotype, complex karyotype, gene expression patterns, and drug sensitivity. These findings demonstrate that the combination of trisomy 21 and GATA1s-generating mutations results in a unique myeloid leukemia independent of whether the GATA1 mutation or trisomy 21 is the primary or secondary event and suggest that there is a unique functional cooperation between GATA1s and trisomy 21 in leukemogenesis. The family histories also indicate that germline GATA1s-generating mutations should be included among those associated with familial predisposition for myelodysplastic syndrome and leukemia.

STUDY OBJECTIVES: Positive airway pressure (PAP) is the second line of treatment for obstructive sleep apnea syndrome in children. It is common practice following initiation of PAP to perform repeat titration polysomnography to re-evaluate the patient’s therapeutic pressure; however, data supporting this practice are lacking. We hypothesized that repeat PAP titration would result in significant setting changes in children with obstructive sleep apnea syndrome. METHODS: We retrospectively analyzed demographic, polysomnographic, and PAP data of children with obstructive sleep apnea syndrome aged 0–18 years who were initiated on PAP and underwent 2 titration studies over a 2-year period. PAP mode and recommended pressure differences between the 2 titrations were compared. RESULTS: 64 children met inclusion criteria. The median (interquartile range) baseline obstructive apnea-hypopnea index and SpO(2) nadir were 14.8 (8.7–32.7) events/h and 88.5% (85–92%), respectively. The mean differences in obstructive apnea-hypopnea index, SpO(2) nadir, and % total sleep time with SpO(2) < 90% between both titrations were negligible, including children with obesity, adenotonsillar hypertrophy, and trisomy 21. Additionally, there was no significant difference in mean PAP pressure between 2 separate titration studies for those on continuous PAP or bilevel PAP. CONCLUSIONS: Overall, repeat PAP titration in children with obstructive sleep apnea syndrome within the timeframe here described did not result in significant changes in PAP mode, continuous PAP pressure, or obstructive apnea-hypopnea index. Based on these data, repeat PAP titration within 2 years of an initial titration does not appear to be necessary. CITATION: Yendur O, Feld L, Miranda-Schaeubinger M, et al. Clinical utility of repeated positive airway pressure titrations in children with obstructive sleep apnea syndrome. J Clin Sleep Med. 2022;18(4):1021–1026.

Aim: To recognize the sociodemographic profile and the periodontal health condition of individuals diagnosed with Down syndrome. Methods: This is a cross-sectional epidemiological study involving individuals diagnosed with Down syndrome in the city of Campina Grande, Paraiba, Brazil. The collection of sociodemographic data was carried out through a semi-structured questionnaire applied to caregivers. The clinical examination was performed in a clinical setting. The sample was non-probabilistic, for convenience (n = 20). Descriptive statistical analysis was performed. For categorical variables, absolute and percentage frequencies were calculated, for quantitative variables, measures of central tendency and variability were calculated. The analyzes were performed with the help of IBM SPSS Statistics software version 20.0. Results: There was a parity among the individuals surveyed in relation to sex, 60% were white, and the average age was 24.6 years (SD = 7.08), with a family income of 2.47 minimum wages (SD = 3.57). Oral hygiene is performed by the individual (89.5%), using a toothbrush and toothpaste (68.4%), twice a day (50%). Most interviewees have already visited the dentist (84.2%), more than 4x (66.7%), less than 6 months ago (53.3%), only in the private sector (50.0%), the main reason for the consultation being prevention (31.3%). It was observed that the average plaque index was high (89.53%). The average bleeding rate on probing was 39.93%, and the average probing depth was 2.09 mm. Conclusion: Studies with groups of individuals with DS who have continuous and systematic preventive dental care have demonstrated an effective improvement in periodontal health dental care, have demonstrated an effective improvement in periodontal health. Uniterms: Down syndrome. Periodontal diseases. Oral health.

Background Children with Down Syndrome (DS) present with neuromuscular disturbances leading to delayed developmental milestones, poor quality of movement and poor balance. The aim of this study is to discuss the role of trunk muscle strength in the functional performance of children with DS. Methodology 28 children were recruited in the study, 14 with DS and 14 age and gender-matched controls. Trunk muscle strength, reaching ability and balance were assessed using a Handheld Dynamometer, Modified Functional Reach test and Pediatric Balance Scale, respectively. Results Children with DS present with poorer trunk muscle strength, reaching ability and balance as compared to typically developing (TD) children. There was a positive correlation between trunk muscle strength and lateral reaching in children with DS. A strong to moderate correlation was observed between the trunk muscle strength and balance in children with DS. Discussion Children with DS demonstrated a significantly weak trunk muscle groups. Lateral reaching distance is reduced due to the poor proximal control and they present with near-normal forward reach distance attributed to compensation using the lower trunk muscles. They exhibit poor balance in the components that require a small base of support. Conclusion Children with DS exhibit weak trunk muscles along with lesser reaching distance and poor balance. Also, trunk muscle strength influences lateral reaching ability. Trunk muscle strength, mainly trunk extensors impacted functional balance in sitting, standing and while performing transfers.

The article deals with a clinical case of primary glucose and galactose malabsorption syndrome in a child with Down syndrome. Difficulty in diagnosis of glucose and galactose malabsorption syndrome in this observation is due to a combination of this disease with other genetic pathology. The article introduces pediatricians and family doctors to the possible comorbidities of various congenital nosological forms., Приведен клинический случай первичного синдрома мальабсорбции глюкозы и галактозы у ребенка с синдромом Дауна. Сложность диагностики синдрома мальабсорбции в данном наблюдении связана с сочетанием заболевания с другой генетической патологией. Статья ознакомит врачей-педиатров и семейных врачей с возможными сочетаниями разных врожденных нозоформ., Наведений клінічний випадок первинного синдрому мальабсорбції глюкози й галактози в дитини з синдромом Дауна. Складність діагностики синдрому мальабсорбції в даному спостереженні пов’язана з комбінацією захворювання з іншою генетичною патологією. Стаття ознайомить лікарів-педіатрів і сімейних лікарів із можливими комбінаціями різних уроджених нозоформ.

Background: Down syndrome (DS) is associated with increased risk for Alzheimer’s disease (AD). In neurotypical individuals, clinical AD is preceded by reduced resting state functional connectivity in the default mode network (DMN), but it is unknown whether changes in DMN connectivity predict clinical onset of AD in DS. Objective: Does lower DMN functional connectivity predict clinical onset of AD and cognitive decline in people with DS? Methods: Resting state functional MRI (rsfMRI), longitudinal neuropsychological, and clinical assessment data were collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 years, range = 42-59 years) over four years, during which 4 transitioned to dementia. Amyloid-β (Aβ) PET data were acquired on 13 of the 15 participants. Resting state fMRI, neuropsychological, and clinical assessment data were also acquired on an independent, slightly younger unimpaired sample of 14 nondemented people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38–61 years). Results: Lower functional connectivity between long-range but not short-range DMN regions predicts AD diagnosis and cognitive decline in people with DS. Aβ accumulation in the inferior parietal cortex is associated with lower regional DMN functional connectivity. Conclusion: Reduction of long-range DMN connectivity is a potential biomarker for AD in people with DS that precedes and predicts clinical conversion.

A 34-year-old patient had her first trimester Down syndrome scan followed by serial ultrasound scans which showed a single intrauterine pregnancy with multiple cystic areas in the anterior placenta. She presented in preterm labour with a breech presentation at 32 weeks and underwent an emergency caesarean section. She delivered a male infant weighing 1750 g. The placental histopathology showed a complete hyatidiform mole. At 4 weeks postpartum, beta-human chorionic gonadotrophin (Bhcg) levels rose from 460 to 836 mIU/mL over 1 week. Metastatic workup revealed prominent pelvic nodes and pulmonary nodules in both lungs. This was discussed at the Multi-Disciplinary Tumour Board and single-agent intramuscular methotrexate was recommended. After chemotherapy, she achieved Bhcg normalisation after three cycles. This case highlights the importance of clinical vigilance even in low-risk patients. Unexpected findings on ultrasound should involve multidisciplinary input with radiology colleagues. A high index of suspicion for gestational trophoblastic disease and close follow-up is imperative.

Myeloid leukemia in children with Down syndrome (ML-DS) is associated with young age and somatic GATA1 mutations. Because of high event-free survival (EFS) and hypersensitivity of the leukemic blasts to chemotherapy, the prior Children’s Oncology Group protocol ML-DS protocol (AAML0431) reduced overall treatment intensity but lacking risk stratification, retained the high-dose cytarabine course (HD-AraC), which was highly associated with infectious morbidity. Despite high EFS of ML-DS, survival for those who relapse is rare. AAML1531 introduced therapeutic risk stratification based on the previously identified prognostic factor, measurable residual disease (MRD) at the end of the first induction course. Standard risk (SR) patients were identified by negative MRD using flow cytometry (

Children with Down syndrome (DS) show delayed acquisition of cognitive and functional skills compared to typically developing children. The objective of this study was to accurately describe early development of infants and young children (children hereafter) with DS based on a large recent sample. We carried out repeated measure analysis of the global development quotient (GDQ) and developmental age using data from the Assessment of Systematic Treatment with Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) study (NCT01576705). Because there was no statistically significant difference in the primary endpoint between active treatment and placebo, data from all treatment groups were pooled for post-hoc analysis. Data of 141 children with DS aged 6-18 months at inclusion were analyzed. Mean GDQ decreased over the study period, especially in the youngest age classes ([6-9] and [9-12] months), indicating that acquisition of skills occurred at a slower pace compared to typically developing children. Strongest deficits were observed for motor and hearing and language skills. Only GDQ at baseline correlated significantly with evolution of GDQ. Future studies should aim at elucidating the mechanisms underlying motor and language development. Early pharmacological interventions together with early childhood therapies might be necessary to improve the developmental trajectory of children with DS.

Background\ud Despite recent advances, mortality in children with Down syndrome remains five times higher than in the general population. This study aims to describe the burden, patterns and causes of hospital admissions in infants with Down syndrome, and compare this with infants without Down syndrome in a population-based cohort.\ud \ud Methods\ud This study used data from the Wales Electronic Cohort for Children, a cohort of all children born in Wales between 1990 and 2012. The cohort was generated from routine administrative data, linked to create an anonymised data set within the Secure Anonymised Information Linkage databank. This analysis is based on all infants born between January 2003 and January 2012 who were followed to their first birthday, a move out of Wales, death, or until 31 October 2012 (end of follow-up). Infants with Down syndrome were identified using the Congenital Anomaly Register and Information Service in Wales. Multivariable Cox regression was used to compare the time to first hospital admission. Admission codes were used to identify the commonest indications for hospitalisation and to determine the presence of other congenital anomalies.\ud \ud Results\ud We included 324 060 children, 356 of whom had Down syndrome. Of infants with Down syndrome, 80.3% had at least one hospital inpatient admission during the first year of life, compared with 32.9% of infants without Down syndrome. These first admissions were earlier [median of 6 days interquartile range (IQR) (3, 72) compared with 45 days [IQR 6, 166)] and longer [median of 4 days (IQR 1, 15) compared with 1 day (IQR 0, 3)] than in infants without Down syndrome. The most common causes of admissions were congenital abnormalities, respiratory diseases, conditions originating in the perinatal period and infectious diseases. The presence of other congenital abnormalities increased hospitalisations in all infants, but more so in infants with Down syndrome who spent a median of 21 days in hospital (IQR 11, 47) during their first year of life.\ud \ud Conclusion\ud Infants with Down syndrome are at high risk for early, more frequent and longer hospital admissions. Congenital heart disease and respiratory infections remain a major burden in this population. More research is needed to understand how to better manage these conditions particularly in the first month of life when most admissions occur.

Refereed/Peer-reviewed The genetic basis of the predisposition for Down Syndrome (DS) patients to develop cytokine receptor-like factor 2 rearranged (CRLF2r) acute lymphoblastic leukemia (ALL) is currently unknown. Genes located on chromosome 21 and expressed in hematopoietic cells are likely candidates for investigation of CRLF2r DS-ALL pathogenesis. We explored the high-mobility group nucleosome-binding protein 1 (HMGN1), located in the DS critical region, in an inducible CRISPR/Cas9 knockout (KO) xenograft model to assess the effect of HMGN1 loss of function on the leukemic burden. We demonstrated HMGN1 KO-mitigated leukemic phenotypes including hepatosplenomegaly, thrombocytopenia, and anemia, commonly observed in leukemia patients, and significantly increased survival in vivo. HMGN1 overexpression in murine stem cells and Ba/F3 cells in vitro, in combination with P2RY8-CRLF2, resulted in cytokine-independent transformation and upregulation of cell signaling pathways associated with leukemic development. Finally, in vitro screening demonstrated successful targeting of P2RY8-CRLF2 and HMGN1 co-expressing cell lines and patient samples with fedratinib (JAK2 inhibitor), and GSK-J4 (demethylase inhibitor) in combination. Together, these data provide critical insight into the development and persistence of CRLF2r DS-ALL and identify HMGN1 as a potential therapeutic target to improve outcomes and reduce toxicity in this high-risk cohort of young patients.

Purpose Children with high ametropia who have difficulties with spectacle or contact lens wear benefit from gains in visual function after intraocular collamer lens (ICL) surgery. Here we assess safety by reporting rates and case specifics of peri-operative and longer-term adverse events (AE).[LINE SEPARATOR] SETTING:: St. Louis Children's Hospital at Washington University Medical Center. Design Retrospective Case Series. Methods Clinical data were collated retrospectively for 95 special-needs children (160 eyes) implanted with a Visian ICL over the last 5 years. All surgeries were performed at St Louis Children's Hospital under brief general anesthesia. Follow-up was a mean 2.0 ±1.4 years (range 0.5-5.2). Results Average age at implantation was 9.3 ± 5.2 years (range 1.8-25) and mean pre-operative SEQRE was -11.2 ± 3.9 D (range - 4-22). Sixty-two children (65%) had a neurodevelopmental disorder. The minor AE rate was 2% (3 eyes), consisting of steroid-response ocular hypertension (OHT), which resolved with cessation of topical steroid drops. Endothelial cell loss averaged 8.1 % over 2 years, comparable to that reported in ICL implanted adults. The most common major AE (4%, 7 eyes) was post-operative pupillary block, requiring revision of the peripheral iridotomy. One child (0.6%, 1 eye) with self-injurious behavior required repair of a wound leak. One child (0.6%, 1 eye) with Down syndrome developed a cataract 2.8 years after ICL surgery. And one child (0.6%, 1 eye) with severe Autism Spectrum Disorder experienced traumatic retinal detachment 1.2 years after implantation. Conclusion The most common major AE among our Visian ICL cohort was pupillary block due to closure of the iridotomy. Overall, the AE rate was low in this higher risk, difficult-to-manage population of special-needs children.

Down syndrome-associated arthritis (DA) is underrecognized, and current therapies used for juvenile idiopathic arthritis (JIA) appear to be poorly tolerated and less effective in patients with DA. The objective of this study was to characterize clinical manifestations and therapeutic preferences in DA compared to JIA, using the new Childhood Arthritis and Rheumatology Research Alliance (nCARRA) registry.In a case-control study, between July 2015 and March 2019, patients with a diagnosis of JIA and Down syndrome (DS) were identified and matched by age, sex, and JIA subtype to patients who have JIA without DS. Collected data included demographic characteristics, disease characteristics, laboratory results, treatment exposure, and outcome measures.A total of 36 children with DA and 165 with JIA were identified. Most patients presented with polyarticular rheumatoid factor-negative disease. At entry into the nCARRA registry, there were minimal differences between the groups, and at the last visit there were significant differences (P0.05) for multiple outcome measures. Patients with DA and those with JIA had similar therapeutic exposure to disease-modifying antirheumatic drugs (DMARDs) and biologics, but those with DA had more DMARD-related adverse events (93% versus 25%) and biologic therapy ineffectiveness (60% versus 17%).There was little difference between patients with DA and those with JIA at baseline, and similar therapy was implemented for those in the nCARRA registry; however, at the last visit, the patients with DA had greater disease burden. Additionally, there were more DMARD-related adverse events and biologic ineffectiveness for those patients with DA. More research is needed to determine differences in pathophysiology and optimal therapeutic approaches.

OBJECTIVE To evaluate the impact of implementing cell-free DNA (cfDNA) testing on gestational age (GA) at termination of pregnancy in a French perinatal network. METHODS We conducted a retrospective study. All women having undergone a termination of pregnancy between 1 January 2012 and 31 December 2017 were included. We compared the periods before and after the introduction of second-line cfDNA testing, which started on 1 January 2015. Throughout the study period, the invasive procedures were foetal karyotyping and chromosomal microarray analysis. The primary study outcome was GA at termination. The secondary outcomes were GA at termination for trisomy 21 and the frequency and GA at the time of invasive procedures. RESULTS During the 6-year study period, 840 women underwent termination. The median GA at termination before and after the implementation of cfDNA testing was 19.4 and 19.0 weeks, respectively (p = 0.38). Although the frequency of termination for trisomy 21 increased significantly from 23% to 32% (p

BACKGROUND: Trisomy 21 (T21) patients often have elevated pulmonary vascular resistance, which may result in suboptimal cavopulmonary connection (CPC) following Glenn or Fontan operations. The purpose of this study was to assess in a nationwide, multi-institution cohort of CPC patients the impact of T21 on patient morbidity, mortality, and resource utilization. METHODS: A total of 23,271 CPC pediatric patients (2004 – 2019) at 50 U.S. hospitals were evaluated using the Pediatric Health Information System (PHIS) database. Univariable and multivariable regression analyses were used to assess risk-adjusted associations between Down syndrome and other risk factors and postoperative measures of morbidity, mortality, lengths of stay (LOS) and cost of hospitalization. RESULTS: The overall prevalence of T21 among Glenn and Fontan patients was 1.5% (199/13,268) and 0.8% (78/1,003), respectively. Among both CPC cohorts, T21 status significantly increased unadjusted mortality, hospital lengths of stay and total costs of hospitalization compared to non-T21 CPC patients (all P < 0.001). T21 patients also incurred a higher incidence of prolonged mechanical ventilation compared to non-T21 patient in both Glenn and Fontan patients (P < 0.001). Multivariable regression analysis further estimated that T21 patients are associated with a 5.5-fold increase in mortality (P < 0.001) compared to non-T21 patients. Lastly, T21 patients had increased long-term mortality compared to their peers. CONCLUSIONS: Trisomy 21 significantly increases risk-adjusted morbidity, inpatient mortality, long-term mortality and resource utilization following cavopulmonary connections. Further investigation is needed to clarify modifiable patient-level and center-specific risk factors to improve outcomes for T21 patients.

The aim of this investigation was to describe the craniofacial and oral characteristics of children and/or adolescents with and without Down syndrome (DS). A bibliographic search of the Medline database (via PubMed), Scopus and SCIELO was performed using the keywords "craniofacial characteristics", "dental characteristics" and "Down syndrome". Systematic reviews, observational cross-sectional and longitudinal studies were included. On the contrary, case reports, letters to the editor, editorials and opinion articles were excluded. 251 articles were recovered, and only 30 fulfilled the selection criteria. DS patients were characterized by reduced dimensions of the maxillary bone, mandible, and skull base, compared to normal patients. Likewise, some of these abnormalities influenced more frequent presentation of a class III malocclusion in these patients. On the other hand, this population group showed a higher prevalence of periodontal diseases, less risk of dental caries, and the presence of alterations in the tongue, lips, dental development and palate morphology. The quality of life of these individuals is affected by difficulties in swallowing, talking, eating or breathing through the nose. In conclusion, the craniofacial and oral characteristics of DS patients present various alterations compared to healthy patients, and these alterations have a negative impact on their quality of life.

With more and more reproductive-aged women opting to pursue genetic screening during pregnancy, health care professionals must understand the variety of testing options available as well as the advantages and limitations of each testing option. Presently, no single screening test is universally believed to be superior because the combination of the specific test and the population being tested determines the range of potential identifiable conditions as well as the positive predictive values. As a result, pre- and posttest counseling are not always straightforward and may require discussions with multiple specialists including genetic counselors, obstetricians, and pediatricians/neonatologists. The purpose of this review is to summarize the screening options currently available to pregnant women to determine their risk of having a child affected by a chromosomal disorder. Screening for chromosomal abnormalities using ultrasonography, maternal serum analytes, cell-free DNA, and preimplantation genetic testing will be discussed here. Advances in the field, including the possible future use of cell-based noninvasive prenatal screening (NIPS) as a more accurate method for genetic screening and the incorporation of screening for copy number variants (microdeletions and duplications) into traditional cell-free NIPS will also be reviewed.

BACKGROUND Children with leukemia and Down syndrome (DS) are at higher risk of acute treatment toxicities than those without DS. Whether late toxicity risks are also elevated is unknown. METHODS The authors identified all patients diagnosed with leukemia before the age of 18 years in Ontario, Canada between 1987 and 2013 and who survived greater than 5 years since their last pediatric cancer event. Survivors were divided into those with and without DS, matched by birth year, sex, leukemia type, and receipt of radiation. DS survivors were matched to individuals with DS without childhood cancer (DS controls) in a 1:10 ratio. Outcomes were identified through linkage to population-based health services databases. RESULTS DS survivors (n = 79) experienced inferior overall survival compared to non-DS survivors (n = 231) (20-year overall survival, 81.7% ± 6.8% vs 98.3% ± 1.2%; hazard ratio [HR], 12.8; P < .0001) and to DS controls (n = 790; 96.3% ± 1.2%; HR, 5.4 P < .0001). Pulmonary and infectious deaths were noted among DS survivors. There was no difference in the incidence of congestive heart failure between DS survivors and either control cohort, nor of hearing loss or dementia between DS survivors and DS controls. CONCLUSIONS DS survivors were at substantially higher risk of late mortality than non-DS survivors or DS controls. This excess risk was not attributable to cardiac- or subsequent malignant neoplasm-related late effects, historically main causes of premature death among non-DS survivors. Chronic morbidities associated with DS were not increased compared to DS controls. DS-specific surveillance guidelines may be warranted.

Neurofibromatosis type 1 (NF1) is a common neurocutaneous disorder characterized by development of pigmentary skin changes, neurogenic tumors, and other manifestations involving multiple organ systems. Penetrance is complete, though expressivity is quite variable even among the family members. Given that NF1 is a common hereditary condition, existence of a second genetic disorder in NF1 patients is not unexpected. During comprehensive evaluations of individuals with NF1, we encountered 11 patients with dual diagnosis who contributed to phenotypic complexity and challenges for long-term management. Examples include Prader-Willi Syndrome, Autosomal Dominant Polycystic Kidney Disease, Down syndrome, infantile myofibromatosis, Craniosynostosis, cleft lip and palate, 47,XYY, 22q11.2 duplication, 15q13.3 deletion syndrome, and BRCA2- and ATM- related cancer predisposition syndromes. Presence of dysmorphism, developmental delay, atypical tumors, and family history of other genetic disorders including cancers appears as determinants to consider a second genetic etiology and helps to differentiate from an extreme phenotypic spectrum of NF1. Clinicians should have high index of suspicion to exclude coexisting disorders, as apart from providing comprehensive medical care. This also has potential implications in genetic counseling. Long-term effects of the synergistic mechanisms leading to phenotypic complexity and patient outcomes are yet to be characterized, with follow-up needed.

BACKGROUND: Down syndrome (DS) is the most common genetic disorder in children. Children with DS tend to have various comorbid due to developmental abnormalities of chromosome 21, such as congenital heart defects, hearing loss, otitis media, eye disorders, obstructive sleep apnea, thyroid hormone disorders, gastrointestinal atresia, hip joint dislocation, leukemia, and Hirschsprung’s disease. Moreover, they also show cognitive impairments in concentration, communication, memory, and the ability to carry out tasks. Caput Scale/Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT-CLAMS) is one of the developmental assessment instruments to screen for cognitive disorders. AIM: Hereby, we aimed to find the association of comorbid with developmental quotient in DS children. Data were obtained from medical record with sample age 0–18 years and suffering from DS. METHODS: This was observational analytic study with cross-sectional approach, conducted in DS children age 0–18 years who were treated in Sanglah Hospital in 2018. Characteristic data and comorbid were obtained from medical record, meanwhile, development status was assessed using Caput Scale/CAT-CLAMS. Chi-square was applied to determine the association between comorbidities and development quotient (DQ) in DS children. RESULTS: A total of 32 children with DS were treated in Sanglah Hospital during 2018 with median age was 2 years old and dominated by female patient (71.9%). Several comorbidities were found such as endocrine disorders in 27 children (84.3%), congenital heart disease (CHD) in 16 children (50%), and other comorbid including microcephaly, congenital cataract, palatoschizis, gastrointestinal defects, and congenital talipes equinovarus in 13 children (40.4%). The most common endocrine disorders was congenital hypothyroidism (81.25%), while the most common CHD was patent ductus arteriosus (25%). Bivariate Chi-square analysis showed significant association between comorbid and DQ (PR = 1.4 [95% CI 0.95–1.97], p = 0.03). CONCLUSION: We found an association between comorbidities and DQ in DS children.

BackgroundIndividuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross-sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS.MethodBaseline SIB, BPT and DLD performances from 100 individuals (no dementia=68, possible dementia=16 & probable dementia=16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression.ResultsThe SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC)=0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC=0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC=0.77 and 0.67, respectively).ConclusionsResults suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS.

To evaluate the risk factors for crusted scabies in children in France. The retrospective multicenter study, conducted in France, of children (aged 18 years) with profuse and/or crusted scabies confirmed by dermoscopy and/or microscopy. Data were obtained using a standardized questionnaire. We included 20 children. The mean age was 4.5 years, and 70% of the patients were girls. Their medical history revealed a neurological pathology (agenesis of the corpus callosum; n = 1, 5.0%), prematurity (n = 1, 5.0%), Down syndrome (n = 1, 5.0%), atopic dermatitis (n = 2, 10%), and asthma (n = 2, 10.0%). Fifteen (75.0%) children were treated with steroids before being diagnosed with scabies: 12 (60.0%) with topical steroids, one (5.0%) with a systemic steroid, and two (10.0%) with inhaled steroids. One child (5.0%) lived in a precarious environment. The mean duration of pruritus was 3.4 months, and that of the skin lesions was 3.1 months. The most commonly affected areas for crusted scabies were the palms/hands (66.7%) and the armpits (33.3%). Thirteen children (65.0%) were hospitalized, 14 (70.0%) were treated with ivermectin and all received topical treatments; 85.7% were cured within an average of 38 days, but one child had a relapse 3 months later in the form of common scabies.Conclusion: The main risk factor for developing crusted scabies in France was the misdiagnosis and the use of corticosteroids, especially topical forms typically used in "healthy" children. Management of the children was effective and similar to that used in adults. What is Known: • Crusted scabies is an extremely contagious disease which is rarely reported in infancy, especially in healthy children. • The main risk factors include immunosuppression, physical debilitation, and intellectual disability. What is New: • The main risk factor of severe scabies in this study was delayed diagnosis associated with the use of topical or systemic corticosteroids. • The treatment was successful in 85.7% of cases, and 65% of children needed to be hospitalized.

The aim of this research was to provide to eight children with Down Syndrome a syllable-processing software program that drew their attention to phonological and orthographic syllables. The children participated in a 10-hour training course (spread over 5 weeks) that used an experimental design with four assessment sessions, the first two of which were used to obtain a baseline in literacy skills. The effect of training was assessed just after training and two months later. A significant effect on decoding was observed at medium term after training. All children progressed in at least one domain, either in phonological skills, in decoding, or in word reading. Four children progressed in decoding and word reading. This study confirms the appropriateness of using phonetic approaches to reading instruction in order to stimulate learning to read in children with Down Syndrome. The syllable-based training facilitates the construction of associations between letters and syllables—the “syllabic bridge”—and could be a faster and easier way to learn letter-sound correspondences in French.

Introduction GATA1 mutation plays an important role in initiating transient abnormal myelopoiesis (TAM) and in the clonal evolution towards acute megakaryoblastic leukaemia (AMKL) associated with Down syndrome (DS). This study aimed to develop and validate the clinical utility of a complementary DNA (cDNA) analysis in parallel with the conventional genomic DNA (gDNA) Sanger sequencing (Ss), as an initial screening test for GATA1 mutations. Methods GATA1 mutations were evaluated using both gDNA and cDNA in 14 DS patients using Ss and fragment analysis (FA), respectively. Results The detection sensitivity of conventional gDNA sequencing was limited in low blast percentage TAM (LBP-TAM); however, cDNA-based Ss readily detected all the pathognomonic GATA1 mutations. The cDNA-based FA readily detected GATA1 frameshift mutation with a reliable sensitivity ranging from 0.005% to 0.01% of clonal cells. Conclusions GATA1 mutations are heterogeneous; therefore, we would like to propose a dual cDNA and gDNA analysis as a standard diagnostic approach, especially for LBP-TAM. cDNA-based FA promises an excellent sensitivity for detecting frameshift GATA1 mutations in the longitudinal clonal evolution towards AMKL without using a patient specific primer.

To establish a risk prediction model and the clinical value of trisomy 21 using alpha-fetoprotein variants L2 (AFP-L2) combined with maternal serum biomarkers and nuchal translucency (NT) thickness in early pregnancy. A retrospective case–control study was conducted. The subjects were divided into the case group (n = 40) or the control group (n = 40). An enzyme-linked immunosorbent assay was used to measure the maternal serum AFP-L2 level in both groups. The AFP-L2 single-index or multi-index combined risk model was used to predict the efficiency of trisomy 21. The best cut-off value and area under the curve (AUC) were determined to evaluate the predictive efficacy of different risk models constructed by AFP-L2. The maternal serum AFP-L2 level in the case group was 1.59 (0.61–3.61) Multiple of medium (MoM), which was higher than 1.00 (0.39–2.12) MoM in the control group (P P P

Adults with Down syndrome (DS) are at risk for Alzheimer’s disease. Despite sharing trisomy 21, however, there is variability in the age of disease onset. This variability may mean that other factors, such as lifestyle, influence cognitive aging and disease timing. The present study assessed the association between everyday life physical activity using an actigraph accelerometer and cognitive functioning and early Alzheimer’s disease pathology via positron emission tomography amyloid-β and tau and diffusion tension imaging measures of white matter integrity in 61 non-demented adults with DS. Percent time in sedentary behavior and in moderate-to-vigorous activity were associated (negatively and positively, respectively) with cognitive functioning (r = −.472 to .572, p

Trisomy 21 is a common birth defect in humans. Screening for trisomy 21 is one of the most important tasks in routine prenatal care and robust noninvasive diagnostics are needed in clinical practice. Urinary proteomics offers a new research platform for diagnostics innovation in this context. We report here new biomarker candidates using urinary proteomics profiling. Specifically, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the proteomes of urine samples from 19 pregnant women (aged 28-44 years) carrying fetuses with trisomy 21 and 22 healthy pregnant women (aged 27-42 years) carrying fetuses with normal karyotype. We identified more than 50 differentially expressed proteins between the trisomy 21 group and healthy group, and most of these proteins were associated with the embryonic development. Importantly, tissue inhibitor of metalloproteinases 2 (TIMP2) and lysosomal-associated membrane protein 2 (LAMP2) were further selected as potential urinary protein biomarkers. We found that the combination of TIMP2 and LAMP2 could differentiate fetuses with trisomy 21 from healthy controls with a sensitivity of 74%, a specificity of 82%, and an area under the receiver operating characteristic curves (AUC) value of 0.82 (95% confidence interval, 0.69-0.95). We conclude that TIMP2 and LAMP2 offer promise as biomarker candidates and warrant further clinical research in larger study samples. These findings further our understanding of the pathological processes involved in fetal trisomy 21 and are poised to accelerate the development of new noninvasive potential biomarkers for trisomy 21 prenatal screening.

Vitamin D is a fat-soluble secosteroid prohormone that is produced on the skin by contact with sunlight. Through various metabolic changes in the body, it transforms into a hormone known as calcitriol, with a key role in the calcium and phosphate metabolism (1). Vitamin D serves plenty of functions in the body. Therefore, its deficiency may cause musculoskeletal symptoms such as bone pain, muscle weakness, gait difficulty, skeletal deformity, in addition to extraskeletal symptoms such as autoimmune diseases, cardiovascular diseases, and neuropsychiatric diseases (2). Down Syndrome occurs as a result of trisomy, which occurs due to an extra copy of the whole or part of the long arm of chromosome 21 and is the most commonly known cause of delay in development. DS affects 1 in every 787 liveborn babies (3). DS is often accompanied by distinctive craniofacial features, congenital heart disease and immune, musculoskeletal and endocrine system abnormalities (4,5). In patients with this syndrome, various environmental and hormonal factors such as hypotonia, low physical activity, poor calcium and vitamin D intake, intrauterine growth restriction, hypogonadism and thyroid dysfunction may contribute to bone mass and quality (6,7). Among all the others, vitamin D may have a crucial role in the health of these people. Vitamin D levels differ with many factors, including exposure to sunlight, dietary intake, and supplement use (8,9). There is a lack of scientific evidence on the prevalence and severity of vitamin D deficiency in children with DS. Hence, this study aimed to determine vitamin D deficiency in children with DS, from infancy to toddler and particularly during the preschool period, and to raise awareness on the matter.

Micro Abstract Few cancer centers from developing countries have described the impact of COVID-19 on pediatric cancer patients. Seventy-six pediatric oncology patients with COVID-19 infection were recruited. Most patients had a favourable outcome with sixty-day overall survival of 86.8%. Mortalities occurred only among patients with critical forms of infection. The potential benefits of remdesivir in pediatric oncology patients require further studies., Introduction : Sufficient data pertaining to the impact of the Coronavirus disease-2019 (COVID-19) on pediatric cancer patients is still lacking. The aim of this prospective study was to describe clinical management and outcomes of COVID-19 in pediatric oncology patients. Patients and Methods : Conducted between May 1st and November 30, 2020, this study included 76 pediatric oncology patients with confirmed COVID-19. Remdesivir (RDV) was the antiviral therapy used. Results : The median age of patients was 9 years. Sixty patients were on first line treatment. Hematological malignancies constituted 86.8% of patients. Severe to critical infections were 35.4% of patients. The commonest symptom was fever (93.4%). Chemotherapy was delayed in 59.2% of patients and doses were modified in 30.2%. The sixty-day overall survival (OS) stood at 86.8%, with mortalities occurring only among critical patients. Of sixteen acute leukaemia patients in the first induction therapy, 13 survived and 10 achieved complete remission. A negative RT-PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (p=0.008 and 0.002, respectively). Better OS was associated with regression of radiological findings after 30 days from infection (p=0.002). Forty-five patients received RDV, 42.1% had severe and critical forms of infection compared to 25.7% in the No-RDV group and yet OS was comparable in both groups. Conclusion : Most paediatric cancer patients with COVID-19 should have good clinical outcomes except for patients with critical infections. Cancer patients can tolerate chemotherapy including induction phase, alongside COVID-19 treatment. In severe and critical COVID-19, RDV might have a potential benefit.

An organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further.

Background: Ketotic hypoglycemia (KH) without an identifiable underlying metabolic or hormonal disease is historically named idiopathic KH. The prevalence is unknown, but idiopathic KH is considered the most frequent cause of hypoglycemia beyond the neonatal period. KH in Down syndrome (DS) has not been reported. Methods: We conducted a web-based survey on KH in DS through the non-profit patient organization Ketotic Hypoglycemia International. The responses were evaluated for consistency with KH by two authors. Two DS patient histories with documented KH were shared in more details. Results: Survey data on 139 DS patients were obtained. After validation, 10 patients (7.2%) had reported episodes of documented hypoglycemia, ketosis, and/or symptoms compatible with KH beyond the neonatal period. Glucose concentrations ranged 1.2-2.9 mmol/L; betahydroxybutyrate was up to 5.5 mmol/L during hypoglycemia. One girl had trisomy 21 with no response to i.m. glucagon also had a heterozygous Xp22.23 deletion including GYG2, which protein, glycogenin 2, is a substrate for glycogen synthase. Treatment with extended release cornstarch was effective. Conclusion: This is the first demonstration of a possible high prevalence of KH in DS. Even though this finding needs to be confirmed in other research settings, identification of KH in DS could have a dramatic impact, as simple treatments with cornstarch, protein and frequent meals may prevent KH attacks and, analogous to other conditions with KH, improve growth, stamina and prevent overeating and obesity. GYG2 deletion may contribute to KH in DS, resembling glycogen storage disease type 0.

Objective We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome. Case report A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free β-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766–90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20–30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16. Conclusion Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

BACKGROUND Pulmonary hypertension (PH) has serious short- and long-term consequences. PH is gaining increasing importance in high risk groups such as Down syndrome (DS) as it influences their overall survival and prognosis. Hence, there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management. AIM To determine the prevalence of PH in children with DS. METHODS The authors individually conducted a search of electronic databases manually (Cochrane library, PubMed, EMBASE, Scopus, Web of Science). Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion. The words used in the literature search were “pulmonary hypertension” and “pulmonary arterial hypertension”; “Down syndrome” and “trisomy 21” and “prevalence”. The data were analyzed by Comprehensive Meta-Analysis Software Version 2. Risk of bias assessment and STROBE checklist were used for quality assessment. RESULTS Of 1578 articles identified, 17 were selected for final analysis. The pooled prevalence of PH in these studies was 25.5%. Subgroup analysis was carried out for age, gender, region, year of publication, risk of bias and etiology of PH. CONCLUSION This review highlights the increasing prevalence of PH in children with DS. It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management. Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.

Craniofacial clefts are extremely rare deformities. Tessier's classification is a widely accepted system that is based on clinical, radiographical, and surgical observations. The Tessier No. 0 cleft most commonly affects the upper lip, nose, and palate. This case presentation aims to report the outcome of a modified presurgical alveolar molding (PAM) appliance used in the treatment of an infant with Tessier No. 0 cleft as an alternate approach to mold such defects before surgery. The modified PAM appliance consisted of reciprocal parts connected by a helix. The segments were approximated by stripping the appliance at the midline in a V-shaped manner and the force was exerted by the extraoral elastics. The procedure gave results in 8 weeks, which may be regarded as a reasonable duration. The anterior cleft gap, which was 13 mm before the treatment, was reduced to 3 mm after the treatment by using modified PAM appliance. On a 21- month follow-up period, oral reshaping was regarded successful due to stability of the improved oral mold.

Summary Adults with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and are at very high risk of developing early-onset dementia, which is now the leading cause of death in this population. Diagnosis of dementia remains a clinical challenge because of the lack of validated diagnostic criteria in this population, and because symptoms are overshadowed by the intellectual disability associated with Down syndrome. In people with Down syndrome, fluid and imaging biomarkers have shown good diagnostic performances and a strikingly similar temporality of changes with respect to sporadic and autosomal dominant Alzheimer's disease. Most importantly, there are no treatments to prevent Alzheimer's disease, even though adults with Down syndrome could be an optimal population in whom to conduct Alzheimer's disease prevention trials. Unprecedented research activity in Down syndrome is rapidly changing this bleak scenario that will translate into disease-modifying therapies that could benefit other populations.

Down syndrome (DS) is associated with certain structural and functional disorders in the whole visual system. The purpose was to compare retinal and choroidal thickness using swept-source optical coherence tomography (SS-OCT) in DS subjects with controls. This cross-sectional study included 100 eyes of 52 DS subjects and 78 eyes of 39 matching age and axial length controls. Our results showed that inner or outer retinal and ganglionar thickness showed no significant differences between DS and control group (p>0.05). However, retinal foveal thickness (rFT), ganglion foveal thickness (gFT) were significantly higher in DS group than in controls, whereas choroidal foveal thickness (cFT) and some choroidal quadrants of inner and outer rings were significantly lower (p

Objective: To determine the needs and level of coping in siblings of people with Down Syndrome. Methods: Descriptive, cross-sectional study, carried out in 2016. Sample consisted of 30 siblings of people with Down Syndrome between 6 and 60 years old. Using non-probability convenience sampling. Two instruments were used to collect the information: a) a validated sociodemographic and needs survey of the siblings, designed by the authors, and b). Callista Roy adaptation and coping survey validated. Results: 60% of the siblings report not having felt judged by other people when presenting their brother/sister with Down syndrome. 73.3% of the siblings did not receive information about Down Syndrome from a nursing professional, the need to strengthen the nursing care provided to the siblings of people with disabilities in this regard is evident. 53.3% of these present a medium level of coping with respect to the condition of having a brother with Down syndrome. Conclusion: Identified needs were: time needs, affective needs, family needs, social needs, economic and access to information needs. Highlighting these needs allows the nursing professional to identify and consider the siblings of people with Down Syndrome have different needs than the rest of the family nucleus. Where interventions aimed at reducing the harmful effects and enhancing those characteristics of gain related with having a brother with Down Syndrome.

The key parameters of anatomical deformations of the facial bones and the cranium, which cause speech disorders in children with Down syndrome, are discussed in the review article.

Use of inter-pupillary distance (IPD) for objective evaluation of ocular hypertelorism and hypotelorism is recommended to corroborate diagnosis of syndromic conditions. In view of complete absence of serial data on growth of IPD, this study aims to unfold auxological dynamics of IPD in Down syndrome (DS) children of Indian origin. Inner canthal distance (ICD) and outer canthal distance (OCD) were measured on a total of 1,125 (male: 752, female: 373) DS children, aged 0 to 3 months to 10 years at 6 monthly age intervals using a “Digimatic Sliding Caliper” in the Growth Laboratory/Growth Clinic of the Institute. Using Feingold and Bossert (1974) formula, IPD at each age was calculated from ICD and OCD measured among male and female DS children. IPD, like OCD and ICD increased un-interruptedly among DS children. IPD grew rapidly up to 5 years thereafter, its rapidity became slower. Boys in general, possessed larger IPD than girls, however, gender differences became statistically significant up to first 4 years of life. Our study children possessed significantly smaller IPD as compared with their normal Indian counterparts. None of our DS children depicted ocular hypertelorism while hypotelorism, was noticed amongst 4.9% male and 16.8% female DS patients. Comparison with normative IPD data failed to establish existence of ocular hypertelorism in DS children (

INTRODUCTION: Motor skills, an important foundation for language and communication, are considerably delayed in children with Down syndrome (DS) and fragile X syndrome (FXS). However, the impact of these impairments on expressive and receptive communication and phenotypic specificity of these associations remains unknown. METHOD: Study participants included 37 children with DS (chronological age(M) (CA(M))=20.38; nonverbal mental age(M) (NVMA(M))=13.19) and 37 children with FXS (CA(M)=19.; NVMA(M)=13.16) matched on chronological and nonverbal mental age. RESULTS: Results showed syndrome-specific profiles across motor and communication domains, where children with DS scored significantly higher than children with FXS on communication domains, but lower on gross motor. Findings revealed significant associations between domains of motor and communication for both groups, but phenotypic specificity in the magnitude of association between fine motor and receptive communication in that the strength of the association was significantly stronger for children with DS. DISCUSSION: Findings demonstrate the importance of early motor abilities for the development of communication for both children with DS and those with FXS. Implications for phenotypic specificity and targeted intervention are discussed.

BACKGROUND Despite presenting higher risk of dementia, mild cognitive impairment (MCI) is not well defined in Down syndrome population. OBJECTIVE We aimed to describe cognitive and neuropsychological patterns associated with MCI in Down syndrome individuals. METHOD Two groups of adults with Down syndrome (control and prodromal) were studied throughout 3 years. Two linear mixed models and a model including the variables that best predicted group membership were built. RESULTS Behavioural Regulation Index (BRI) (Behaviour Rating Inventory of Executive Function test) and the model composed of BRI, abstraction and delayed verbal memory were the variable and model best predicting group membership, respectively. CONCLUSION Suggest a diagnosis of MCI when BRI is the earliest change perceived by caregivers and this is combined with low scores in abstract thinking, and when an amnesic pattern in delayed verbal memory is observed, but adaptive skills are preserved.

Background Maternal serum free beta human chorionic gonadotrophin (free β-hCG) is used as a biomarker in first trimester screening for fetal Down’s syndrome. Production of free β-hCG can occur in vitro in a time- and temperature-dependent manner; thus, the current Scottish screening protocol states samples must be received by the laboratory within 72 h. To assess the validity of the protocol, an audit was conducted to determine the impact of transit time on maternal serum free β-hCG multiple of median (MoM) values in the Scottish screened population. Methods Corrected MoM values from antenatal screening carried out over one year (April 2017 to March 2018) were stratified according to sample transit time and compared. To investigate possible environmental temperature effects, the data were split according to season and maternal serum free β-hCG concentrations from summer and winter compared. Results Of the 28,368 samples included in the study, 24,368 were received on the day of phlebotomy or after one day in transit. Only 1.5% of samples were received after 3 days in transit. The difference in maternal serum free β-hCG MoM values due to transit time was not significant. No statistical difference was found between maternal serum free β-hCG concentrations from samples collected in summer and winter months. Conclusion The current sample receipt protocol in use by the Scottish Down’s syndrome screening programme is fit for purpose.

This study was aimed at investigating the effectiveness of assisted therapy (ACT) on manual dexterity in older adults with Down syndrome (DS). Nine older participants with DS, aged 31–52 years old, completed a 30-min stationary cycling session, three times per week for eight weeks of ACT intervention, pedaling at 35% higher than voluntary speed. Another eight older participants with DS, aged 30–51 years old, participated in the voluntary cycling (VC) intervention, pedaling at voluntary speed, as the comparison group. Manual dexterity measured by the Purdue Pegboard Test, and outcome expectations measured by the Exercise Perception Scale, were tested before and after the interventions. After both exercise interventions, the results showed that the non-dominant hand and bimanual subtests of the Purdue Pegboard were significantly improved. The outcome expectations were elevated at marginally statistical level as well. It is speculated that continuous cycling exercise, VC and ACT, may stimulate peripheral sensory input to the motor areas that led to the improvements in manual dexterity and exercise perception. Even though the exact mechanisms are still unknown, the implication of our results showed that VC and ACT can improve manual dexterity in aging DS population.

Background: Down Syndrome (DS) is one of the most common birth conditions in the United States of America, with approximately 5300 births annually, resulting in an estimated birth prevalence of 12.6 per 10,000 live births and a population prevalence in the USA since 2010 of 6.7 per 10,000 inhabitants. Children with DS have complex medical challenges that present due to changes in their immune system that results in increased rates of infection, malignancy, and autoimmune disease. Juvenile Dermatomyositis (JDM) is a rare, autoimmune disease, and the most common inflammatory myopathy of childhood. Reports suggest an increased incidence of arthritis in children with DS, but there have been no reports of JDM in children with DS. Additionally, those with DS pose unique challenges with an increase in adverse effects and ineffectiveness of immunosuppressive therapy. Case : We describe the first case of an adolescent female with DS who developed JDM with a positive anti-p155/140 antibody and characteristic clinical phenotype. We discuss increased awareness of autoimmune disease in adolescents with DS and clinical considerations for therapy with immunosuppression. Conclusion: Adolescents with DS are at increased risk for autoimmune disease, including JDM. Awareness, early recognition of the signs and symptoms of autoimmune disease in those with DS is important, so appropriate therapy can be implemented.