Comprehensive Care for Adults with Down Syndrome in Primary Care Settings.

This review article aims to bridge the knowledge gap in providing comprehensive care to adults with Down syndrome (DS) in primary care settings. Despite the increasing prevalence of adults with DS, there is a significant lack of familiarity and comprehensive guidelines for their health care among primary care physicians. This often results in subpar health promotion, preventive screenings, and individualized care. This article attempts to provide guidance for healthcare providers on previsit preparation, clinic visit characteristics, testing and screening considerations, and decision making/guardianship for adults with DS. By emphasizing a patient-centered approach, this review aims to enhance the quality of care, reduce associated morbidity and mortality, and ultimately improve the health outcomes of adults with DS.

Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

Orofacial myofunctional and polysomnographic characteristics of children with Down syndrome and obstructive sleep apnea: a pilot study. / Características miofuncionais orofaciais e polissonográficas de crianças com Síndrome de Down e apneia obstrutiva do sono: estudo piloto.

PURPOSE: To investigate oropharyngeal structures and functions in a pediatric population with Down Syndrome (DS) and obstructive sleep apnea (OSA) and to correlate with the apnea/hypopnea index (AHI) and sleep questionnaires. METHODS: 12 Children with DS and OSA, between the age of 4 and 12 years old, underwent polysomnography (PSG); sleep questionnaires, Pediatric Sleep Questionnaire (PSQ) and Obstructive Sleep Apnea-18 (OSA-18); and speech-language evaluation using the Short Evaluation of Orofacial Myofunctional Protocol (ShOM). RESULTS: There was a positive correlation between ShoM higher scores and the apnea-hypopnea index (AHI) and between ShoM and the number of hypopneas. The orofacial myofunctional alterations observed in the studied group were: oral breathing, alteration in lip tonus and competence, tongue posture at rest and in swallowing, and occlusal alteration. There was also an increased risk for OSA according to the sleep questionnaires, as well as the presence of obesity and overweight, but without correlation with the severity of OSA. CONCLUSION: All DS children show alterations in orofacial characteristics, higher scores being associated to severe OSA. Orofacial myofunctional evaluation may help to identify different phenotypes in Down syndrome children with Obstructive sleep Apnea, enhancing the need for a multidisciplinary approach.

OBJETIVO: Investigar as estruturas e funções orofaríngeas de uma população pediátrica com Síndrome de Down (SD) e apneia obstrutiva do sono (AOS) e correlacionar com o índice de apneia/hipopneia (IAH) e questionários do sono. MÉTODO: 12 Crianças com SD e AOS, entre 4 e 12 anos, foram submetidas à polissonografia (PSG); questionários do sono, Pediatric Sleep Questionnaire (PSQ) e Obstructive Sleep Apnea-18 (OSA-18); e triagem fonoaudiológica por meio do Short Evaluation of Orofacial Myofunctional Protocol (ShOM). RESULTADOS: Verificou-se uma correlação positiva entre pontuações mais elevadas no ShOM e o índice de apneia hipopneia (IAH) e entre o ShOM e número de hipopneias. As alterações miofuncionais orofaciais observadas no grupo estudado foram: respiração oral, alteração no tônus e competência labial, na postura de língua em repouso e na deglutição e alteração oclusal. Verificou-se também, um risco aumentado para AOS conforme os questionários do sono, bem como presença de obesidade e sobrepeso, mas sem correlação com a gravidade da AOS. CONCLUSÃO: Todas as crianças apresentaram alterações miofuncionais orofaciais, sendo que escores mais altos no ShOM, ou seja, um maior comprometimento miofuncional orofacial, estavam associados à maior gravidade de AOS, sugerindo que a avaliação miofuncional orofacial dentro de uma abordagem multidisciplinar pode auxiliar na identificação de fatores de risco para AOS em crianças com SD.

Successful recovery from cardiac arrest due to atlantoaxial subluxation in Down syndrome: a case report.

INTRODUCTION: Down syndrome is the most common chromosomal abnormality associated with intellectual impairments. Unexpected deaths are common with this disease. There are certain difficulties in clarifying the cause of death because the manifestations may be quite diverse and involve many organ systems. Atlantoaxial subluxation is a dangerous complication of Down syndrome, as it may lead to cervical cord-medullary compression. CASE PRESENTATION: Herein, we present a case of Down syndrome in a patient who completely recovered from cardiac arrest due to atlantoaxial subluxation. The neck was immobilized during post-cardiac arrest care, and the patient underwent surgery after 14 days. The patient could walk independently and was discharged 3 months later. At the last follow-up 5 years after surgery, the patient's general condition was good. DISCUSSION: Physicians should be aware that atlantoaxial instability can cause cardiac arrest in patients with genetic syndromes.

Cerebrovascular disease emerges with age and Alzheimer's disease in adults with Down syndrome.

Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis. Enlarged PVS and infarcts appear to develop in the early 30s, while microbleeds, WMH, amyloid, and tau emerge in the mid to late 30s. Age-residualized WMH were higher in women, in individuals with dementia, and with lower body mass index. Participants with hypertension and APOE-ε4 had higher age-residualized PVS and microbleeds, respectively. Lifespan trajectories demonstrate a dramatic cerebrovascular profile in adults with Down syndrome that appears to evolve developmentally in parallel with AD pathophysiology approximately two decades prior to dementia symptoms.

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

Rate and management of tympanic membrane perforations in children with Down syndrome and middle ear disorder.

OBJECTIVE: To characterize the management and outcomes of observation versus surgical intervention of tympanic membrane (TM) perforations in children with Down syndrome (DS). In addition, to estimate the prevalence of TM perforations in children with DS. METHODS: Retrospective case review analysis of TM perforation rate in children with DS with history of tympanostomy tube (TT) insertion at a tertiary pediatric referral center. Patients were divided into observation or surgical intervention groups and then further evaluated for the type of intervention, the number of required procedures, and success rate of hearing improvement. Risk factors contributing to perforations were analyzed, including TT type, number of TT surgeries, and perforation size. RESULTS: The TM perforation rate in children with DS with TT history was 7.0 %. Tympanoplasty was performed in 41.5 % of perforated ears with a success rate of 53.1 %. There was no statistical difference between the surgical intervention and observation groups regarding perforation characteristics or TT number and type, but the surgical intervention cohort was older. Hearing improvement based on postoperative pure tone average (PTA) threshold was noted in the successful surgical intervention group. CONCLUSION: The rate of TM perforations in children with DS after TTs is comparable to the general population. Improved PTA thresholds were noted in the surgical success group influencing speech development. The overall lower success rate of tympanoplasty in patients with DS emphasizes the need to factor in the timing of surgical intervention based on the predicted age of Eustachian tube maturation.

Persistent omphalomesenteric duct in an infant with trisomy 21.

We present the case of a term newborn with trisomy 21 who presented to the paediatric emergency department with periumbilical flare and green-brown discharge from a clamped umbilical cord, initially suspected to be omphalitis. However, it was noticed later, that when the infant strained or cried, a thick, bubbling and offensive green-brown discharge came out of the clamped umbilical cord with umbilical flatus. An ultrasound abdomen and umbilical cord confirmed the presence of a persistent omphalomesenteric duct (POMD). He was then transferred to the paediatric surgical unit. There, he underwent a laparotomy and surgical resection of the POMD and was discharged home 2 days later.

Dysregulation of the Immune System in a Natural History Study of 1299 Individuals with Down Syndrome.

Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 patient control cohort at the Mount Sinai Health System in New York, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, are exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life.

Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2: preliminary findings.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aß), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aß deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

Assessing Uveitis Risk following Pediatric Down Syndrome Diagnosis: A TriNetX Database Study.

Background and Objectives: The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. Materials and Methods: This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. Results: A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89-1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 [CI: 0.68-2.72]), 0-5 years (HR: 1.34 [CI: 0.75-2.39]), and 6-18 years (HR: 1.15 [CI: 0.67-1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87-2.56]) or males (HR: 0.82 [CI: 0.48-1.41]) with DS compared to their respective non-DS comparators. Conclusions: Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.

Outcomes of surgical treatment of patellar instability in children with Down syndrome.

BACKGROUND: patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed). MATERIALS AND METHODS: This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score. RESULTS: The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39-56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31-74), and at final follow-up, it was 92.2 ± 4.4 (range: (88-98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39-62), and at final follow-up it was 92.4 ± 5.3 (range: 82-96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury. CONCLUSIONS: Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved. LEVEL OF EVIDENCE: IV; retrospective case series.

Kidney and urogenital abnormalities in Down syndrome: a meta-analysis.

BACKGROUND: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. RESULTS: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. CONCLUSIONS: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in a Young Child With Down Syndrome.

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA.

Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life.

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

Analysis of Down syndrome newborn outcomes in three neonatal intensive care units in Rio de Janeiro, Brazil.

OBJECTIVE: The aim of this study was to analyze the outcomes of newborns with Down syndrome admitted to three neonatal intensive care units in the city of Rio de Janeiro, Brazil. METHODS: A retrospective cohort study was conducted by analyzing the medical records between 2014 and 2018 of newborns with Down syndrome admitted to three neonatal intensive care units. The following variables were analyzed: maternal and perinatal data, neonatal malformations, neonatal intensive care unit intercurrences, and outcomes. RESULTS: A total of 119 newborns with Down syndrome were recruited, and 112 were selected for analysis. The most common maternal age group was >35 years (72.07%), the most common type of delivery was cesarean section (83.93%), and the majority of cases were male (53.57%). The most common reasons for neonatal intensive care unit hospitalization were congenital heart disease (57.66%) and prematurity (23.21%). The most common form of feeding was a combination of human milk and formula (83.93%). The second most common malformation was duodenal atresia (9.82%). The most common complications during neonatal intensive care unit hospitalization were transient tachypnea of the newborn (63.39%), hypoglycemia (18.75%), pulmonary hypertension (7.14%), and sepsis (7.14%). The mean length of stay in the neonatal intensive care unit was 27 days. The most common outcome was discharge (82.14%). Furthermore, 12.50% of newborns were transferred to an external neonatal intensive care unit, and 6% died. CONCLUSION: Newborns with Down syndrome are more likely to be admitted to the neonatal intensive care unit, and the length of hospital stay is longer due to complications related to congenital malformations common to this syndrome and prematurity.

[Use of murine models for the study of obstructive sleep apnea syndrome in Down syndrome]. / Utilisation des modèles murins pour l'étude du syndrome d'apnées obstructives du sommeil dans le syndrome de Down.

Down syndrome (DS), or trisomy 21, is a genetic disorder caused by the presence of an extra copy of chromosome 21, leading to various characteristic physical features as well as developmental and cognitive delays. Obstructive sleep apnea syndrome (OSAS) is a common disorder in both adult and pediatric patients with DS. Several characteristics of DS may contribute to the development or worsening of OSAS. Numerous murine models of DS exist. A number of studies have explored apneas and the risk of upper airway obstruction in these models, but up until now, only in adulthood.