Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome

Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.

Congenital heart“Challenges”in Down syndrome

In this editorial,we comment on the article by Kong et al published in the recent issue of the World Journal of Cardiology.In this interesting case,the authors present the challenges faced in managing a 13-year-old patient with Down syndrome(DS)and congenital heart disease(CHD)associated with pulmonary arterial hypertension.In this distinct population,the Authors underscore the need for early diagnosis and management as well as the need of a multidisciplinary approach for decision making.It seems that the occurrence of CHD in patients with DS adds layers of complexity to their clinical management.This editorial aims to provide a comprehensive overview of the intricate interplay between DS and congenital heart disorders,offering insights into the nuanced diagnostic and therapeutic considerations for physicians.

Realizing the potential of exploiting human IPSCs and their derivatives in research of Down syndrome

Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.

Brain metabolic profile assessed by magnetic resonance spectroscopy in children with Down syndrome:Relation to intelligence quotient

BACKGROUND Down syndrome(DS)is one of the most common causes of intellectual disability.Children with DS have varying intelligence quotient(IQ)that can predict their learning abilities.AIM To assess the brain metabolic profiles of children with DS and compare them to standard controls,using magnetic resonance spectroscopy(MRS)and correlating the results with IQ.METHODS This case-control study included 40 children with DS aged 6-15 years and 40 age and sex-matched healthy children as controls.MRS was used to evaluate ratios of choline/creatine(Cho/Cr),N-acetyl aspartic acid/creatine(NAA/Cr),and myoinositol/creatine(MI/Cr(in the frontal,temporal,and occipital lobes and basal ganglia and compared to controls and correlated with IQ.RESULTS Children with DS showed significant reductions in NAA/Cr and MI/Cr and a non-significant reduction in Cho/Cr in frontal lobes compared to controls.Additionally,we observed significant decreases in NAA/Cr,MI/Cr,and Cho/Cr in the temporal and occipital lobes and basal ganglia in children with DS compared to controls.Furthermore,there was a significant correlation between IQ and metabolic ratios in the brains of children with DS.CONCLUSION Brain metabolic profile could be a good predictor of IQ in children with DS.

Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.

Prevalence of pulmonary hypertension among children with Down syndrome:A systematic review and meta-analysis

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.

Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics

Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications.Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies.Methods:We analyzed a prospective cohort of 52 pediatric patients(age 3 to 35 months)looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery,defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography.This corresponds to a mean pulmonary arterial pressure of>20 mmHg.Clinical,echocardiographic and hemodynamic parameters were investigated.Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters.Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio(PAP/SAP)obtained per patient during the first 6 h of postoperative care.Results:Among the factors that were investigated as possible predictors,perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis(p<0.030).Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass(r=0.70,p<0.001),and it was higher in subjects with Down syndrome than in nonsyndromic individuals(p=0.003).Early postoperative PAP/SAP was the only predictor selected using multivariate analysis.It was characterized as an independent predictor after adjustments for possible confounders.An early postoperative PAP/SAP of>0.35 was 76%sensitive and 74%specific at predicting a systolic pulmonary arterial pressure of>30 mmHg 6 months after surgery(hazard ratio with 95%CI 8.972[2.428–33.158],p=0.002).Conclusion:The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome,and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.

Application of intelligent algorithms in Down syndrome screening during second trimester pregnancy

BACKGROUND Down syndrome(DS)is one of the most common chromosomal aneuploidy diseases.Prenatal screening and diagnostic tests can aid the early diagnosis,appropriate management of these fetuses,and give parents an informed choice about whether or not to terminate a pregnancy.In recent years,investigations have been conducted to achieve a high detection rate(DR)and reduce the false positive rate(FPR).Hospitals have accumulated large numbers of screened cases.However,artificial intelligence methods are rarely used in the risk assessment of prenatal screening for DS.AIM To use a support vector machine algorithm,classification and regression tree algorithm,and AdaBoost algorithm in machine learning for modeling and analysis of prenatal DS screening.METHODS The dataset was from the Center for Prenatal Diagnosis at the First Hospital of Jilin University.We designed and developed intelligent algorithms based on the synthetic minority over-sampling technique(SMOTE)-Tomek and adaptive synthetic sampling over-sampling techniques to preprocess the dataset of prenatal screening information.The machine learning model was then established.Finally,the feasibility of artificial intelligence algorithms in DS screening evaluation is discussed.RESULTS The database contained 31 DS diagnosed cases,accounting for 0.03%of all patients.The dataset showed a large difference between the numbers of DS affected and non-affected cases.A combination of over-sampling and undersampling techniques can greatly increase the performance of the algorithm at processing non-balanced datasets.As the number of iterations increases,the combination of the classification and regression tree algorithm and the SMOTETomek over-sampling technique can obtain a high DR while keeping the FPR to a minimum.CONCLUSION The support vector machine algorithm and the classification and regression tree algorithm achieved good results on the DS screening dataset.When the T21 risk cutoff value was set to 270,machine learning methods had a higher DR and a lower FPR than statistical methods.

The Effectiveness of 6 Months Hydrotherapy Program Based on Halliwick Concept on the Respiratory System of Down Syndrome Children

The aim of the study was to investigate the effect of a hydrotherapy program on FVC, FEV, PEF, RR and SaO2 on children with Down syndrome over six months and to compare it with a conventional respiratory physiotherapy program. Eighteen children, with Down Syndrome, aged 6 - 11 years (9.53 ± 0.454), divided into two groups of nine, the intervention group (IG), that participated in the hydrotherapy program and the control group (CG) participated in the classical physiotherapy program. We calculated mean values of FVC, FEV, PEF, RR and SaO2 before and after six months intervention for both groups. There was a statistically significant improvement in all factors for both groups. However, were statistically more significant for the intervention group (IG). Based on a specific protocol of intervention in the water and at the same time with a group of children who participated in a similar program of classical respiratory physiotherapy, it was found to be statistically more important than the second group in improving respiratory function. We recommend the use of hydrotherapy as a complementary therapy that should be part of the weekly program of these children in addition to the existing treatments they attend.

Daily Life and Planning for the Future of Ageing People with Down Syndrome: Results from a National Study on Caregivers

Background: Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when people who take care of them will not be there anymore (“after we have gone”). Objective: From a biopsychosocial perspective, to investigate the daily life of ageing people with Down Syndrome over 45 years old in order to identify the most important issues in better planning for their future. Methods: A cross-sectional Italian national study was carried out. An ad hoc questionnaire was administered to formal and informal caregivers of aging people with Down Syndrome. Results: 136 family members and health professionals were involved. Most of the people with Down Syndrome live at home, attend a daily center and do many activities. Most of them had never worked and she/he is not at all autonomous. 25% of caregivers declared that, nowadays, there is not planning for the future, and 30.9% of participants who planned their future collected information when it occurred (e.g. when the parents pass away). Conclusions: The aging of people with DS requires attention to the planning of their future. In order to better plan, it is necessary to avoid programming “in emergency”, but for time, keeping in mind of the activities developed by the people, their abilities and all of the elements that have allowed them to live well up to a point of their life.

Demon Genes May Deform Common Syndromes: Collagen VI Gene Change in Down Syndrome Unifies the Medical and Molecular Approach to Hypermobility Disorders

Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.

Graves’ Disease and Down Syndrome: Case Report

Down syndrome (DS) is the most common chromosomal abnormality in humans, and the most frequent cause of mental retardation. Patients affected by this syndrome show an increased prevalence of autoimmune diseases. The most common of those is Hypothyroidism. We present a case report describing the association of Down syndrome with Hyperthyroidism. An 18-year-old patient presented with a history of recurrent throat infections and intermittent diarrhea, having developed a total alopecia areata within one month from the first visit to the physician. After consultations with general practitioners, he was directed to an Endocrinology Ambulatory and diagnosed with a clear case of Graves’ disease associated with Down syndrome. Treatment was started with methimazole 20 mg/day, and after two months, was adjusted to 40 mg/day. The patient reached adequate clinical and laboratory balance after five months of treatment. Thus, the association between Down syndrome and Graves’ Disease is relevant in medical practice, due to its specific characteristics on diagnosis, and the need of an adequate treatment regarding this disease association.

Weight Management of Young Women with Down Syndrome: <i>C-ICAN</i>Meal Plan

Primary care physicians are in a unique position to provide a holistic and individualized care to their patients with Down Syndrome. These patients share common medical problems with general population;however, they often are medically complex and present with cardiac, orthopedic, and endocrine challenges such as overweight-obesity and related comorbidities that occur with more frequency in this unique population. The prevention of overweight-obesity is an important public health issue for both the general population and for the population of individuals with Down Syndrome. If abnormal weight gain is treated early and effectively many secondary comorbidities can be prevented or ameliorated. This case report discusses the impact of implementing a Consistent Individualized Carbohydrate controlled Anti-inflammatory Nutrition plan (C-ICAN) as part of the treatment plan for a young woman with Down Syndrome (DS). The C-ICAN meal plan is a low glycemic load meal plan with 30% to 35% calories from fat, 20% to 25% calories from protein, 40% to 45% calories from carbohydrate, and goal of 25 gm fiber per day. The C-ICAN meal plan combines the Mediterranean diet because of its well-established anti-inflammatory, and cardiovascular benefits, with a high protein and low glycemic-load meal plan to improve satiety and glycemic control. In this case the patient and her caregivers adjusted to a structured meal pattern well, weight balance resulted, and mealtime stress was reduced.

HLA antigens in individuals with down syndrome and alopecia areata

AIM: To describe human leukocyte antigen(HLA) alleles in individuals with Down syndrome and alopecia areata. METHODS: A cross-sectional study was conducted, which evaluated 109 individuals. Ten with down syndrome(DS) and alopecia areata(AA), ten with DS without AA and ten with AA without DS, and their fami-lies. The individuals were matched by gender and age. The following data were computed: gender, age, ethnic group, karyotype, clinical presentation and family history of alopecia areata. Descriptive analysis: measures of central tendency and frequency distribution. Inferential analysis: Fisher's exact test to compare categorical data between the three groups and Kruskal-Wallis ANOVA test for numerical data.RESULTS: Seventy per cent of evaluated individuals in the DS and AA group were male; presented mean age of 18.6(SD ± 7.2) years and 70% were Caucasian. We observed involvement of the scalp, with a single lesion in 10% and multiple in 90% of subjects. It was observed that there is no significant difference in the frequency distributions of the alleles HLA loci A, B, C, DRB1 and DQB1 of subjects studied. However, according to Fisher's exact test, there is a trend(P = 0.089) of DS group to present higher proportions of HLA-A 36 and HLA-B 15 than the AA group and AA and DS group.CONCLUSION: There was a tendency for the DS group, to present proportion of HLA-A 36 and HLA-B 15 higher than the AA group and group of individuals with AA and DS. However, there was no significant difference in the frequency distribution of the alleles.

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age： a prospective study

Background The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age （AMA）. The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome （DS） and compare the trends of choice of screening and amniocentesis among AMA women. Methods A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20~6 weeks. The patients referred were grouped into a screening group （2107 cases） and an amniocentesis group （3297 cases） by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis. Results There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54%o （18/2107）. Twenty- five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7,58%0 （25/3297）. No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group （P=0.928）. The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group （1/131.88 vs. 1/23.78）. With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant （P=0.012）. Conclusions The second trimester serum screening age alone to screen for DS. We suggest educating screening and amniocentesis options. in combination with maternal age was more effective than maternal the patients by recommending AMA women be informed of both

Detection and functional annotation of misregulated microRNAs in the brain of the Ts65Dn mouse model of Down syndrome

Background Brain hypoplasia and mental retardation in Down syndrome （DS） can be attributed to a severe and selective disruption of neurogenesis. Secondary disruption of the transcriptome, as well as primary gene dosage imbalance, is responsible for the phenotype. MicroRNA （miRNA） expression is relatively abundant in brain tissue. Perturbed miRNA expression might contribute to the cellular events underlying the pathology in DS. Methods MiRNA expression profiles in the cerebrum of Ts65Dn mice, a DS model, were examined with a real-time RT-PCR array. MiRNA target gene expression was detected by real-time quantitative PCR and Western blotting. Based on the prediction of their cerebrum-specific targets, the functions of the misregulated miRNAs were annotated by Gene Ontology （GO） enrichment analysis. Results A total of 342 miRNAs were examined. Among them, 20 miRNAs showed decreased expression in the brains of Ts65Dn mice, and some of these belonged to the same family. Two known targets of the miR-200 family, Lfng and Zeb2, were specifically selected to compare their expression in the cerebrum of Ts65Dn mice with those of euploids. However, no significant difference was found in terms of mRNA and protein expression levels of these genes. By enrichment analysis of the cerebrum-specific targets of each miRNA, we found that 15 of the differential miRNAs could significantly affect target genes that were enriched in the GO biological processes related to nervous system development. Conclusion Perturbed expression of multiple functionally cooperative miRNAs contributes to the cellular events underlying the pathogenesis of DS.

Intranasal rapamycin ameliorates Alzheimerlike cognitive decline in a mouse model of Down syndrome

Background:Down syndrome(DS)individuals,by the age of 40s,are at increased risk to develop Alzheimer-like dementia,with deposition in brain of senile plaques and neurofibrillary tangles.Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain,prior and after the development of Alzheimer Disease(AD).The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways,including insulin signaling and autophagy,involved in pathology onset and progression.Within this context,the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena.By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol(InRapa)that maximizes brain delivery and reduce systemic side effects.Methods:Ts65Dn mice were administered with InRapa for 12 weeks,starting at 6 months of age demonstrating,at the end of the treatment by radial arms maze and novel object recognition testing,rescued cognition.Results:The analysis of mTOR signalling,after InRapa,demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR(reduced to physiological levels),which led,through the rescue of autophagy and insulin signalling,to reduced APP levels,APP processing and APP metabolites production,as well as,to reduced tau hyperphosphorylation.In addition,a reduction of oxidative stress markers was also observed.Discussion:These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis,thus ultimately resulting in improved cognition.Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.

Molecular mechanisms of congenital heart disease in down syndrome

Down syndrome(DS),as a typical genomic aneuploidy,is a common cause of various birth defects,among which is congenital heart disease(CHD).40e60%neonates with DS have some kinds of CHD.However,the molecular pathogenic mechanisms of DS associated CHD are still not fully understood.This review summarizes available studies on DS associated CHD from seven aspects so as to provide a crucial and updated overview of what we known so far in this domain.

Prevalence and Parental Awareness of Hearing Loss in Children with Down Syndrome

Background： To establish the prevalence of hearing deficit in children with Down syndrome （DS） in Hong Kong as measured by brainstem auditory evoked potentials （BAEP）. The secondary objective is to examine the agreement between BAEP and clinical questioning in detecting hearing deficit in DS. Methods： Consecutive DS patients attending the Down＇s Clinic in a regional pediatric referral center were recruited into this cross-sectional study. BAEP data performed within 12 months were retrieved. The care-taker was interviewed with a structured questionnaire to detect any symptom of hearing impairment. BAEP findings and clinical questionings were compared in an agreement analysis using quadratic weighted kappa statistics. Results： Filly DS patients （35 male, 15 female, mean age 11.70 years ± 5.74 standard deviation） were recruited. Eighteen patients （36.0%） were identified having hearing deficit by BAEP. Among patients with hearing impairment, 13 patients （72.2%） had a conductive deficit, and most have mild to moderate hearing loss. Five patients （27.8%） had sensorineural deficit and most have moderate to severe degree. Eight （44.4%） had bilateral hearing deficit. Care-takers of 13 patients （26.0%） reported symptoms of hearing impairment, with 9 （69.2%） having mild symptoms, 3 （23.1%） had moderate symptoms and 1 （7.7%） had severe symptoms. The weighted kappa was 0.045 （95.0% confidence interval - 0.138-0.229）, indicating very poor strength of agreement between BAEP and clinical questioning. For patients with conductive hearing impairment, only 1 patients （7.7%） recalled history ofotitis media. Conclusions： The estimated point prevalence of hearing impairment in Chinese DS children in Hong Kong is 36%. Our finding of poor strength of agreement between objective testing and symptom questioning reflects significant underestimation of hearing impairment by history taking alone. In view of the high prevalence and low parental awareness, continuous surveillance of hearing is mandatory for DS patients throughout childhood and adolescence.

Tomography-based definition of keratoconus for Down syndrome patients

Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgeräte,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down syndrome(DS).Methods:In this study,DS patients were enrolled through special needs schools,the National Down Syndrome Society,and relevant non-profit organizations.Diagnoses were made independently by two experienced specialists.Forty Pentacam indices related to corneal thickness,volume,density,keratometry,power,shape,aberration,and elevation were extracted.For each index,the accuracy for KC and KCS diagnosis was evaluated using discriminant analysis and the area under receiver operating characteristic curve(AUROC).From each enrolled case,data from only one eye was entered in the analyses.Results:Analyses were performed on data from 25 KC,46 KCS,and 154 non-ectatic DS eyes.The best discriminants for KC were anterior higher order aberrations(HOA)(cutoff>0.643,AUROC=0.879),posterior vertical coma(cutoff>0.0702μm,AUROC=0.875),anterior vertical coma(cutoff>0.4124μm,AUROC=0.868),and total HOA(cutoff>0.608,AUROC=0.867).The difference between AUROCs were not statistically significant(all P>0.05).For KCS,the best discriminants were minimum corneal thickness(cutoff≤480.0μm,AUROC=0.775),corneal volume(cutoff≤55.3μm,AUROC=0.727)and Belin Ambrosio display-total deviation(BAD-D)(cutoff>2.23,AUROC=0.718)with no significant difference between AUROCs(all P>0.05).Conclusions:In this sample of DS patients,best KC discriminators were HOA and coma which showed good diagnostic ability.For KCS,best predictors were minimum corneal thickness,corneal volume,and BAD-D with relatively good diagnostic ability.Defining a new set of KC diagnostic criteria for DS patients is suggested.