Facial dysmorphism is influenced by ethnic background of the patient and of the evaluator

The evaluation of facial dysmorphism is a critical step toward reaching a diagnostic. The aim of the present study was to evaluate the ability to interpret facial morphology in African children with intellectual disability (ID). First, 10 experienced clinicians (five from Africa and five from Europe) rated gestalt in 127 African non‐Down Syndrome (non‐DS) patients using either the score 2 for ‘clearly dysmorphic’, 0 for ‘clearly non dysmorphic’ or 1 for ‘uncertain’. The inter‐rater agreement was determined using kappa coefficient. There was only fair agreement between African and European raters (kappa‐coefficient = 0.29). Second, we applied the FDNA Face2Gene solution to assess Down Syndrome (DS) faces. Initially, Face2Gene showed a better recognition rate for DS in Caucasian (80%) compared to African (36.8%). We trained the Face2Gene with a set of African DS and non‐DS photographs. Interestingly, the recognition in African increased to 94.7%. Thus, training improved the sensitivity of Face2Gene. Our data suggest that human based evaluation is influenced by ethnic background of the evaluator. In addition, computer based evaluation indicates that the ethnic of the patient also influences the evaluation and that training may increase the detection specificity for a particular ethnic.     

A ‘cure’ for Down syndrome: what do parents want?

Recent advancements in molecular genetics raise the possibility that therapeutics or a ‘cure’ for Down syndrome (DS) may become available. However, there are no data regarding how parents of children with DS perceive the possibility of mitigating specific manifestations such as the intellectual disability (ID) associated with DS, or curing the condition entirely. To explore these issues, we distributed a questionnaire to members of the Lower Mainland Down Syndrome Society in British Columbia, Canada. Questionnaires were completed by 101 parents (response rate = 41%). A majority (61%) viewed the possibility of reversing ID in DS positively, but only 41% said that they would ‘cure’ their child of DS if it were possible. Twenty‐seven percent of respondents said they would not ‘cure’ their child, and 32% were unsure if they would ‘cure’ their child. The most commonly cited motivation for opting for a ‘cure’ was to increase their child's independence. However, parental attitudes' towards a ‘cure’ for DS were complex, affected by ethical issues, perceived societal values, and pragmatic factors such as the age of the individual and long‐term care‐giving burden. These findings could be used by healthcare professionals supporting families who include a member with DS and to direct future research.     

保定地区38例唐氏综合征的细胞遗传学分析

本文通过对38例唐氏综合征的细胞遗传学检查,全部做外周血染色体核型分析。结果单纯性21-三体综合征占92.10%,易位型21-三体占7.89%嵌合型21-三体未发现。结论染色体异常是唐氏综合征的根本原因,因此产前筛查意义重大。     

Financial impact of a specialized Down syndrome clinic: Implications and support for institutional support of specialty care clinics

Individuals with Down syndrome (DS) have specific health care needs and require additional screening and surveillance for commonly associated conditions. The American Academy of Pediatrics (AAP) Committee on Genetics has provided clinical guidance in “Health Supervision for Children and Adolescents with Down Syndrome.” Many DS specialty centers (DSC) have been created, in part, to help ensure adherence to these guidelines. The primary purpose of this work is to determine the financial impact of a specialized DSC. A retrospective chart review was completed for all patients seen in DSC for fiscal year 2018 (June 2018–June 2019). Charts were reviewed to ascertain the financial impact of a DSC to a healthcare system by calculating total downstream charges (using CMS Chargemaster) as a surrogate marker for financial impact. Five-hundred-seventy-four patient encounters were conducted; 99 were new patient visits. Annual charges totaled $1,399,450. The 1–5-year-old age group accounted for greater than half of all charges. The greatest proportion of charges resulted from sleep studies and other diagnostic testing (55%). DS clinics are extremely helpful in ensuring that children receive guideline-based care. Taking into account downstream revenue, specialized DSCs are also financially beneficial to the institutions with whom they are affiliated.     

Motor strategies and motor programs during an arm tapping task in adults with Down Syndrome

Slow movements and atypical patterns of muscle activation are well-known features of Down Syndrome (DS). Some studies attribute these features to a deficit in voluntary motor commands and preprogramming of actions, that lead subjects with DS to be more reliant on feedback control. In the present study, we evaluated the movement strategies of 13 adult subjects with DS and of 22 age-matched controls (N) during an arm tapping task. By means of quantitative motion analysis, our aim was to describe movement differences in DS respect to typical population and provide a means of interpreting such differences in terms of the underlying different control processes. The results highlighted distinct motor strategies for the tapping task in the two groups, with DS relying more on the trunk motion and N relying on the elbow motion to accomplish the task. Furthermore, DS corrected their wrist trajectory more than N subjects, giving shape to multi-peaked velocity profiles. Longer duration of the trials and a higher index of curvature were found in DS. The results suggest that subjects with DS rely more on feedback control, whereas they have problems with movement planning and feed-forward control. The different strategy operated by subjects with DS leads to a different task performance.     

Studying Down syndrome recognition probabilities in Thai children with de‐identified computer‐aided facial analysis

Craniofacial dysmorphism recognition is the first step in diagnosing most genetic syndromes. However, the number of genetic syndromes is enormous, and the specific facial features are difficult to memorize. For clinical practice, recent advances in artificial intelligence can be of use. One such tool, Face2Gene (FDNA, Inc., Boston, MA), is an innovative free group of applications, that helps clinicians recognize possible genetic syndromes from patients’ facial two‐dimensional photos. The initial data set used to train this technology consisted primarily of Caucasian patients. Because ethnic differences affect patients’ facial features, the recognition probability in Asian patients may be limited. Our aim was to test the technology's recognition probability on Thai children with Down Syndrome (DS) as compared to Thai children without DS (non‐DS). Two separate control groups of Thai non‐DS children, either unaffected or having other syndromes, were included. Frontal photographs were obtained from all the participants. All 30 children with DS were recognized as DS in the top 10 syndrome‐matches (100% sensitivity), and 27 were in the first ranking of suggested syndromes. Eighteen non‐DS were recognized as DS (87.2% specificity) with an accuracy of 89%. We present a scientific basis for this novel tool, useful in the clinic where patients are of a different ethnicity unfamiliar to the evaluator. However, Face2Gene cannot be considered a replacement for clinicians’ knowledge of phenotypes. Further studies on other genetic syndromes/ethnicities being identified by software algorithms are needed.     

Prevalence of unsuspected abnormal echocardiograms in adolescents with down syndrome

The purpose of this article is to describe the prevalence of cardiac disease previously undiagnosed in healthy asymptomatic children and adolescents with Down syndrome (DS). Subjects with DS ages 10–20 years were recruited from two sites, the Children's Hospital of Philadelphia (Philadelphia, PA) and Children's National Health System (Washington, DC) for a cross‐sectional study of body composition and cardiometabolic risk. Echocardiographic and clinical data were collected from patients enrolled in the parent study of cardiometabolic risk. Nine (6%) new cardiac diagnoses were identified out of 149 eligible patients. All new findings resulted in outpatient referrals to pediatric cardiology. Current guidelines recommend screening all newborns with DS for congenital heart disease. Older patients with DS may benefit from rescreening.     

Parents' perspective on having a child with Down Syndrome in France

In 2011, Skotko, Levine, and Goldstein asked parents who had children with Down Syndrome (DS) in the United States how they felt about having a child with DS. The purpose of the present study was to ask the same questions to parents living in France so that this information could be shared with new and expectant parents. The results were also compared to the findings of Skotko, Levine, and Goldstein (2011a) to see whether some parental feelings might be universally shared and to discuss the differences observed. This web‐based survey was shared with a number of DS organizations and online DS communities. Of the 369 respondents living in France, 99% indicated that they loved their son or daughter with DS; 98% were proud of their child with DS; 78% felt that their outlook on life was more positive because of their son or daughter with DS; 12% felt embarrassed by their child with DS; and 7% expressed regret for having a child with DS. A significant number of respondents admitted that raising a child with DS was not without challenges. Nevertheless, most respondents indicated that their son or daughter with DS had had a positive impact on their life and that of their family and that they were happy to have their child.     

Global and local processing in Williams syndrome, autism, and Down syndrome: perception, attention, and construction

Global and local processing was studied in Williams Syndrome (WS), autism (AS), and Down Syndrome (DS) using perception, attention, and construction tasks. Past research has suggested an abnormal bias toward global processing in DS and, in contrast, an abnormal local bias in both WS and AS. Until now, no study has investigated whether the local processing bias in WS and AS has a different or similar underlying cause. Findings here suggest a common underlying mechanism, namely a bias in attention toward local processing. Results also indicate a global bias in attention in DS. This study finds no evidence to support predictions of the hierarchical deficit theory (Mottron & Belleville, 1993) as an explanation of hierarchical processing deficits in AS or DS, but does find support for hierarchical deficit theory in a subset of WS individuals. This study finds evidence of cognitive heterogeneity in WS, consistent with Porter and Coltheart (2005).     

Global and Local Processing in Williams Syndrome,Autism, and Down Syndrome: Perception,Attention, and Construction

Global and local processing was studied in Williams Syndrome (WS), autism (AS), and Down Syndrome (DS) using perception, attention, and construction tasks. Past research has suggested an abnormal bias toward global processing in DS and, in contrast, an abnormal local bias in both WS and AS. Until now, no study has investigated whether the local processing bias in WS and AS has a different or similar underlying cause. Findings here suggest a common underlying mechanism, namely a bias in attention toward local processing. Results also indicate a global bias in attention in DS. This study finds no evidence to support predictions of the hierarchical deficit theory (Mottron & Belleville, 1993) as an explanation of hierarchical processing deficits in AS or DS, but does find support for hierarchical deficit theory in a subset of WS individuals. This study finds evidence of cognitive heterogeneity in WS, consistent with Porter and Coltheart (2005).     

Clinical trials in children with Down syndrome: issues from a cognitive research perspective

Clinical and translational research play a key role in the transition of basic research discoveries to effective therapies. In Down syndrome (DS), these research approaches are not well utilized or developed to test new therapies to improve cognitive and/or adaptive function in this population. This article reviews the history of clinical trial research in children with DS from a cognitive research perspective and discusses important issues relevant to the conduct of well designed clinical trials for this population. Specific issues addressed include: funding, study design, study medication, subject recruitment and retention, safety, and efficacy challenges. The Duke Down Syndrome Research Team's program of clinical research of cholinesterase inhibitors for individuals with DS serves as the model application for the identified research principles. It is hoped that this article will raise awareness of the unmet need for clinical research in the cognitive and adaptive function of individuals with DS, especially children with DS.     

Clinical manifestations of the deletion of Down syndrome critical region including DYRK1A and KCNJ6

A relatively small region of human chromosome 21 (Hsa21) is considered to play a major role in Down syndrome (DS) phenotypes, and the concept of a Down syndrome critical region (DSCR) has been proposed. The goal of the phenotype–genotype correlation study is to discover which genes are responsible for each DS phenotype. Loss of the genomic copy numbers of Hsa21 can give us important suggestion to understand the functions of the involved genes. Genomic copy number aberrations were analyzed by micro‐array‐based comparative genomic hybridization (aCGH) in 300 patients with developmental delay. Partial deletions of Hsa21 were identified in three patients with developmental delay, epilepsy, microcephaly, and distinctive manifestations. Two of the patients had mosaic deletions of 21q22‐qter including a part of DSCR; one of whom whose mosaic ratio was higher than the other showed more severe brain morphogenic abnormality with colpocephaly, which was similar to the previously reported patients having pure deletions of 21q22‐qter, indicating the critical region for cortical dysplasia at this region. The remaining patient had the smallest microdeletion with 480 kb in DSCR including DYRK1A and KCNJ6. Although we could not identify any nucleotide alteration in DYRK1A and KCNJ6 in our cohort study for 150 patients with mental retardation with/without epilepsy, this study underscores the clinical importance of DSCR not only for DS but also for developmental disorders. © 2010 Wiley‐Liss, Inc.     

Atypical Down syndrome and partial trisomy 21

A case of “atypical” Down Syndrome (DS), where the proposita did not exhibit all of the clinical features of DS and had de novo partial trisomy 21, was studied. Results from phenotypic, chromosome banding and superoxide dismutase (SOD) gene dosage studies suggest a karyotype of 46,XX,-12, + t(12pter to 12qter::21q21 to 21q22.?2). Additional studies of such atypical cases will provide more precise sublocalization for both gene and phenotypic mapping of the bands that are responsible for the DS phenotype.     

The contribution of the citrate pathway to oxidative stress in Down syndrome

Inflammatory conditions and oxidative stress have a crucial role in Down syndrome (DS). Emerging studies have also reported an altered lipid profile in the early stages of DS. Our previous works demonstrate that citrate pathway activation is required for oxygen radical production during inflammation. Here, we find up‐regulation of the citrate pathway and down‐regulation of carnitine/acylcarnitine carrier and carnitine palmitoyl‐transferase 1 genes in cells from children with DS. Interestingly, when the citrate pathway is inhibited, we observe a reduction in oxygen radicals as well as in lipid peroxidation levels. Our preliminary findings provide evidence for a citrate pathway dysregulation, which could be related to some phenotypic traits of people with DS.     

Contributions of a specialty clinic for children and adolescents with Down syndrome

We investigated what added value, if any, a Down syndrome specialty clinic brings to the healthcare needs of children and adolescents with Down syndrome. For this quality improvement study, we performed a retrospective chart review of 105 new patients with Down syndrome, ages 3 and older, seen during the inaugural year of our specialty clinic. We asked how many of our patients were already up‐to‐date on the healthcare screenings recommended for people with Down syndrome. We further analyzed what tests we ordered, which referrals we suggested, and, ultimately, what new diagnoses of co‐occurring medical conditions were made. Only 9.8% of our patients were current on all of the recommended Down syndrome healthcare screenings. Parents came to clinic with a variety of concerns, and after laboratory tests, radiologic studies, and subspecialty referrals, we made many new diagnoses of gastrointestinal conditions (e.g., constipation and celiac disease), seasonal allergies, dermatologic conditions (e.g., xerosis), behavioral diagnoses (e.g., autism spectrum disorder and disruptive behavior not otherwise specified), and clarifications of neurologic conditions. A Down syndrome specialty clinic can identify and address many healthcare needs of children and adolescents with Down syndrome beyond that which is provided in primary care settings. © 2013 Wiley Periodicals, Inc.     

Constitutional chromosome abnormalities and acute leukemia

A review on the association between acute leukemias (AL) and constitutional chromosome abnormalities (CCA) is presented. AL, myeloblastic or lymphoblastic according to age are 16 to 20 times more frequent in Down Syndrome (DS) children than in non DS children. The incidence of acquired chromosome abnormalities is similar in leukemic cells of DS and non DS patients but the type of anomalies, in the leukemic myeloblastic cells of DS, are different: hyperdiploidy, excess of C, F and G. Gain of chromosomes 8, 19 and 22 would characterize leukemic myeloblasts in an early stage of differentiation. Recent data on transient leukemoid reactions show that a 21 in DS appears to be predisposing factor in the development of AL. Association between AL and other balanced or unbalanced CCA appears until now to be fortuitous.     

Down syndrome: common otolaryngologic manifestations

Otolaryngologic or ear, nose, and throat (ENT) problems are common in children with Down Syndrome (DS). This includes problems with chronic ear infections and chronic middle ear effusions with associated hearing loss, airway obstruction, and sleep apnea, as well as problems with chronic rhinitis and sinusitis. In addition, many of these ENT problems require surgical interventions, and there are special anesthesia considerations that need to be addressed in children with DS. These include subglottic stenosis, post-operative airway obstruction, and cervical spine concerns. As the care of children with DS has become more consistent and proactive, outcomes from the treatment of these ENT manifestations have improved. Aggressive interventions, both medical and surgical, have led to a decreased incidence of hearing loss, good control of the chronic rhinitis, and a better awareness of the incidence of sleep apnea and sleep-disordered breathing in individuals with DS. These common otolaryngologic manifestations of DS are reviewed with recommendations for ongoing care and monitoring.     

Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

A randomized controlled trial of an online health tool about Down syndrome

PurposeWe sought to determine if a novel online health tool, called Down Syndrome Clinic to You (DSC2U), could improve adherence to national Down syndrome (DS) guidelines. We also sought to determine if primary care providers (PCPs) and caregivers are satisfied with this personalized online health tool.MethodsIn a national, randomized controlled trial of 230 caregivers who had children or dependents with DS without access to a DS specialist, 117 were randomized to receive DSC2U and 113 to receive usual care. The primary outcome was adherence to five health evaluations indicated by national guidelines for DS. DSC2U is completed electronically, in all mobile settings, by caregivers at home. The outputs—personalized checklists—are used during annual wellness visits with the patient’s PCP.ResultsA total of 213 participants completed a 7-month follow-up evaluation. In the intention-to-treat analysis, the intervention group had a 1.6-fold increase in the number of indicated evaluations that were recommended by the primary care provider or completed compared with controls. Both caregivers and PCPs reported high levels of satisfaction with DSC2U.ConclusionsDSC2U improved adherence to the national DS health-care guidelines with a novel modality that was highly valued by both caregivers and PCPs.