Clinical Features Of Down Syndrome Research Articles

Evaluation of clinical profile to diagnose Down syndrome with respect to karyotyping as gold standard: a cross-sectional study

Background: Down syndrome (DS) is a genetic disorder characterized with trisomy of chromosome 21 with a high prevalence among countries like India. DS patients present clinically with intellectual disability, congenital heart defect and other major abnormalities. Early diagnosis of DS and intervention with supportive care improves the patient care. To study the efficacy/use of Hall’s and Fried’s scoring system in diagnosing DS confirmed with karyotyping.Methods: The patients presented with dysmorphology, intellectual disability or other clinical features of DS are assessed for inclusion using Hall’s and Fried’s scoring in which patients with score ≥3 are included and considered positive. These patients are further confirmed with karyotyping. The results of Hall’s and Fried’s scoring are comparing against karyotyping results to check for its efficacy.Results: The cross-sectional study conducted found males as majorly affected sex (60.4%) for DS and the mean age of child at diagnosis as 6.69±4.84 months in infant stage and 61.86±60.16 months after infant stage. Flat face was present in 100% followed by up slanting palpebral fissures, protruding tongue, abundant neck skin and little digit clinodactyly. ID is seen in all the patients with CHD in 48.8% population and GI abnormalities in 9.3%. Among CHD’s, VSD is majorly seen followed by AVSD.Conclusions: The study found using combined criteria of both Fried’s and Hall’s score/criteria as an excellent screening test to suspect DS in community level compared to an individual score/criteria.

Cytogenetic and clinical features of down syndrome in malang, east java, indonesia

Introduction: Down syndrome (DS) is the most common chromosomal disorder. DS characterized by multiple congenital anomaly caused by trisomy 21This study was designed to evaluate the karyotype pattern, clinical features and risk factors of patients with Down syndrome.
 Method: Data were obtained from a retrospective analysis of a questionnaire from Down syndrome patients.
 Result: A total of 34 patients were studied, with 67,6% of males. Out of 34 patients, there were 25 children (73,5%) with no cytogenetic test, 4 children (11,7%) with lost cytogenetic test, 3 children (8,82%) with free trisomy (non-disjunction), 1 (2,9%) with translocation, and 1 (2,9%) with mosaics. Maternal age categories showed one mother less than 20 years, two mothers between 21-25 years, four mothers were between 25 and 30 years, 12 mothers were between 31 and 35 years, ten mothers were between 31 and 40 years, and five mothers were over 41 years of age. The most common clinical features in this study are Congenital Heart Disease (CHD), which was recognized in 9 (26,4%) patients with five patients had Atrial Septal Defect (ASD), two patients had ASD and Ventricular Septal Defect (VSD), two patients had Patent Ductus Arteriosus (PDA). All of them followed by dental problems in 8 (23,5%) patients, ophthalmology problems in 6 (17,6%) patients, digestive problems in 4 (11,7%) patients, seizure in 1 (2,9%) patient, hormonal problems in 1 (2,9%) patient, and hearing problem in 1 (2,9%) patient. There is no significant difference in CHD prevalence between each maternal age group (p = 0776, p>0.05).
 Conclusion: Down syndrome has a higher prevalence in males and is frequently seen among mothers between 31 -35 years of age, yet maternal age did not seem to influence CHD prevalence significantly. Early diagnosis and proper screening should be undertaken among these patients.

Down syndrome.

Trisomy 21, the presence of a supernumerary chromosome 21, results in a collection of clinical features commonly known as Down syndrome (DS). DS is among the most genetically complex of the conditions that are compatible with human survival post-term, and the most frequent survivable autosomal aneuploidy. Mouse models of DS, involving trisomy of all or part ofhuman chromosome 21 or orthologous mouse genomic regions, are providing valuable insights into the contribution of triplicated genes or groups of genes to the many clinical manifestations in DS. This endeavour is challenging, as there are >200 protein-coding genes on chromosome 21 andthey can have direct and indirect effects on homeostasis in cells, tissues, organs and systems. Although this complexity poses formidable challenges to understanding theunderlying molecular basis for each of the many clinical features of DS, it also provides opportunities for improving understanding of genetic mechanisms underlying the development and function of many cell types, tissues, organs and systems. Since the first description of trisomy 21, we have learned much about intellectual disability and genetic risk factors for congenital heart disease. The lower occurrence of solid tumours in individuals with DS supports the identification of chromosome 21 genes that protect against cancer when overexpressed. The universal occurrence of the histopathology of Alzheimer disease and the high prevalence of dementia in DS are providing insights into the pathology and treatment of Alzheimer disease. Clinical trials to ameliorate intellectual disability in DS signal a new era in which therapeutic interventions based on knowledge of the molecular pathophysiology of DS can now be explored; these efforts provide reasonable hope for the future.

Serum S100B and intelligence in children with Down syndrome

Background Down syndrome is characterized by physical and mental retardation and caused by chromosome 21 (Hsa21) abnormalities. The S100B is a protein that is overproduced in Down syndrome due to overexpression of chromosome 21 genes. Comorbidities caused by S100B in Down syndrome are cognitive deterioration and early onset of dementia.
 Objective To assess for a possible association between S100B protein and intelligence levels in children with Down syndrome.
 Method This cross-sectional study included students in a special needs school in Padang, West Sumatera, who had the characteristic clinical features of Down syndrome and trisomy 21 by chromosome analysis. Examination of S100B levels was carried out using an enzyme-linked immunosorbent assay (ELISA) method. Intelligence quotient (IQ) was measured using the 4th edition of the Wechlser Intelligence Scale for Children (WISC-IV) method.
 Results A total of 39 children with Down syndrome participated in the study. There were 25 children with mild mental retardation and 15 children with moderate-severe mental retardation. The mean S100B levels were not significantly different between groups [479.1 (SD 204) pg/mL in the mild mental retardation group and 458.7 (SD 158) pg/mL in the moderate-severe mental retardation group; P > 0.05]. The mean S100B level was significantly higher in subjects aged ≤ 10 years than in those aged > 10 years [566.9 (SD 210.0) pg/mL and 434.4 (SD 167.2) pg/mL, respectively (P<0.05)].
 Conclusion There is no association between S100B and intelligence levels in children with Down syndrome. There is a significant association between higher S100B levels and younger age in children with Down syndrome.

Down syndrome phenotype in a boy with a mosaic microduplication of chromosome 21q22

BackgroundDown syndrome, typically caused by trisomy 21, may also be associated by duplications of the Down syndrome critical region (DSCR) on chromosome 21q22. However, patients with small duplications of DSCR without accompanying deletions have rarely been reported.Case presentationHere we report a 5½-year-old boy with clinical features of Down syndrome including distinct craniofacial dysmorphism and sandal gaps as well as developmental delay. Conventional karyotype was normal, whereas interphase FISH analysis revealed three signals for DSCR in approximately 40% of lymphocytes and 80% of buccal mucosa cells. Array-CGH analysis confirmed a 2.56 Mb duplication of chromosome 21q22.13q22.2 encompassing DYRK1A.ConclusionThis presents one of the smallest duplications within DSCR leading to a Down syndrome phenotype. Since the dosage sensitive gene DYRK1A is the only duplicated candidate DSCR gene in our patient, this finding supports the hypothesis that DYRK1A contributes to dysmorphic and intellectual features of Down syndrome even in a mosaic state.

Cytogenetic, epidemiological and clinical profile of children with Down syndrome in Karnataka

IntroductionDown syndrome is one of the best recognized and the most common chromosomal aneuploidy with high life expectancy than other chromosomal aneuploidies. The clinical features are quite distinguishing and easily identifiable, but a karyotype analysis is always better to confirm the diagnosis. It is also needed for calculating the risk of recurrence and for genetic counseling. This study was done to analyze the clinical features, cytogenetic and epidemiological profile of Down syndrome children in Tumkur and Bangalore region of Karnataka. Material and methodsKaryotyping was done in 75 children with clinical features of Down syndrome by standard methods. Information about epidemiological & clinical features was documented. Informed written consent was taken from the parents. Comparison was made in the observed epidemiological profile, clinical features and the karyotype obtained. ResultsAmong the 75 children with clinical features of Down syndrome, 59 had trisomy 21, 11 had translocation and 2 had mosaicism and 3 had a normal karyotype. The mean maternal age was 28.5 years. The prominent abnormalities noted were craniofacial features (71.8%). Characteristic limb abnormalities were also commonly observed (48.4). Congenital heart disease was diagnosed 56.1% cases analyzed. DiscussionEfforts should be made to establish early diagnosis and proper screening. Confirmation of clinical diagnosis by Karyotyping is essential to determine the precise diagnosis, calculate recurrence risk and provide basis for genetic counseling.

Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies

BackgroundThe clinical features of Down syndrome vary among individuals, with those most common being congenital heart disease, intellectual disability, developmental abnormity and dysmorphic features. Complex combination of Down syndrome phenotype could be produced by partially copy number variations (CNVs) on chromosome 21 as well. By comparing individual with partial CNVs of chromosome 21 with other patients of known CNVs and clinical phenotypes, we hope to provide a better understanding of the genotype-phenotype correlation of chromosome 21.MethodsA total of 2768 pediatric patients sample collected at the Genetics Laboratory at Oklahoma University Health Science Center were screened using CGH Microarray for CNVs on chromosome 21.ResultsWe report comprehensive clinical and molecular descriptions of six patients with microduplication and seven patients with microdeletion on the long arm of chromosome 21. Patients with microduplication have varied clinical features including developmental delay, microcephaly, facial dysmorphic features, pulmonary stenosis, autism, preauricular skin tag, eye pterygium, speech delay and pain insensitivity. We found that patients with microdeletion presented with developmental delay, microcephaly, intrauterine fetal demise, epilepsia partialis continua, congenital coronary anomaly and seizures.ConclusionThree patients from our study combine with four patients in public database suggests an association between 21q21.1 microduplication of CXADR gene and patients with developmental delay. One patient with 21q22.13 microdeletion of DYRK1A shows association with microcephaly and scoliosis. Our findings helped pinpoint critical genes in the genotype-phenotype association with a high resolution of 0.1 Mb and expanded the clinical features observed in patients with CNVs on the long arm of chromosome 21.

Profile of clinical features, congenital heart disease and other comorbidities in children with Down syndrome in a tertiary care centre in Nigeria

Background: Down syndrome (DS) is a common chromosomal disorder associated with congenital heart disease (CHD) which could lead to severe morbidity or mortality. Objective: To determine the frequency and spectrum of clinical features, CHD and other comorbidities in children with DS in a tertiary care centre in Nigeria. Method : Consecutive children with clinical features of DS were recruited. The frequency of clinical features and co-morbidities were noted. All the children had echocardiographic evaluation to identify those with CHD. Results : A total of 64 children was recruited of which 36 (56%) were male. Fifty one (80%) had CHD of which atrio-ventricular septal defect (AVSD) was the commonest, being found in 20 (39%) children. Common clinical features present were oblique eyes in 64 (100%), depressed nasal bridge in 60 (94%) low set ears in 53 (83%) and epicanthal folds in 50 (78%). Conclusions : Prevalence of CHD amongst DS children in this study was 80% with AVSD being the commonest. The most prevalent clinical features seen in these children were oblique eyes, epicanthal fold, depressed nasal bridge, low set ears, hypertelorism and hypotonia. Sri Lanka Journal of Child Health , 2018; 47 (1): 50-55

Occurrence of Congenital Heart Disease among Children with Down syndrome: What is the Influence of Maternal Age?

Abstract Background: The occurrence of Down syndrome is strongly dependent on maternal age and incidence varies at various maternal ages. This incidence may differ from one country to another according to the social and environmental factors predominant in such countries. The study aims to document the prevalence of congenital heart defects in patients with Down syndrome, identify the association between maternal age and occurrence of congenital heart disease among these subjects Methods: The study was prospective, cross-sectional and consecutive, involving subjects from two centers which were; a tertiary hospital, a private hospital which is a major cardiology center. Children with clinical features of Down syndrome had transthoracic echocardiography done by a cardiologist. Results: A total of 195 patients with Down syndrome were studied ages between1day to 12years. The mean age + SD were 241.03 + 529.71days and male to female ratio of 1.04:1. The mother’s age range was from 19 to 44years with a mean age + SD of 32.36 + 5.43 years. Up to 16.9% had structurally normal heart. The most common heart defect was atrioventricular septal defect 24.1%. There was no significant association between maternal age and occurrence of congenital heart defects in the subjects. Conclusion: The incidence of congenital heart disease is high among subjects with Down syndrome. Atrioventricular defects were the commonest cardiac defect among the subjects. The incidence of congenital heart defect in the subjects was decreasing from maternal age 36 years and above. Routine cardiac evaluation including echocardiography is recommended for all patients with Down syndrome.

Mosaic double aneuploidy: Down syndrome and XYY

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

Hypochondroplasia due to FGFR3 gene mutation (N540K) and mosaic form of Down syndrome in the same patient

The simultaneous presence of Down syndrome and achondroplasia has rarely been reported in the literature, and our search revealed only six patients with such an association. We are reporting the first case of a patient with Down syndrome and hypochondroplasia. In this patient, Down syndrome was clinically recognised and confirmed by the cytogenetic finding of mosaic karyotype (47,XX,+21/46,XX) shortly after birth. She was subsequently diagnosed with hypochondroplasia at the age of 6 years when disproportional short stature, stocky habitus and macrocephaly were observed. These phenotypic findings were later confirmed by the presence of fibroblast growth factor receptor 3 (FGFR3) gene mutation N540K. The overlapping common clinical features of Down syndrome and hypochondroplasia resulted in delayed diagnosis of hypochondroplasia in our patient and the associated deleterious effect on her linear growth. Her final height is 126.5 cm, which is -3.76 standard deviations (SD) lower than the median height in patients with Down syndrome, and is under the lower borderline of the adult height range for women with hypochondroplasia.

Down-Turner Syndrome (45,X/47,XY,+21): Case Report and Review

We report the case of a 3-yr-old boy with Down-Turner mosaicism and review the previous reports of Down-Turner syndrome with documented karyotyping and clinical features. The patient showed clinical features of Down syndrome without significant stigma of Turner syndrome. Cytogenetic analysis of peripheral blood preparations by using G-banding revealed mosaicism with 2 cell lines (45,X[29]/47,XY,+21[4]). FISH analysis revealed that 87.5% of the cells had monosomy X karyotype and 12.5% of the cells had XY karyotype; trisomy 21 was only detected in the Y-positive cells. We suggest that additional cells should be analyzed and molecular genetic studies should be conducted to rule out double aneuploidy when karyotypes with sex chromosome aneuploidies and mosaicism are encountered, as in our case of Down syndrome mosaic with sex chromosome aneuploidy.

Clinical, Cytogenetic, and Molecular Characterization of a Girl with Some Clinical Features of Down Syndrome Resulting from a Pure Partial Trisomy 21q22.11-qter Due to a De Novo Intrachromosomal Duplication

We report a girl with a de novo pure partial trisomy 21 with some clinical features of Down syndrome. The girl patient presented a flat broad face, brachycephaly, and a flat nasal bridge. She also had upwardly slanted palpebral fissures, epicanthal folds, blepharitis, brushfield spots, and strabismus. Her mouth was wide with downturned corners, prominent lower lip, narrow and furrowed tongue, and short palate. G-banded chromosomal analysis of metaphases in cells from both skin and blood showed a 46,XX karyotype with additional chromosomal material on the distal short arm of one chromosome 21. Parental chromosomes were normal. Molecular analyses with the short-tandem-repeat (STR) marker D21S2039 (interferon-alpha/beta receptor [IFNAR]) (21q22.1) showed a triallelic pattern. Subtelomeric fluorescent in situ hybridization (FISH) analyses, LSI 13 (retinoblastoma 1 [RB1])/LSI 21(21q22.13-q22.2), and whole chromosome painting probes specific for chromosome 21 showed trisomy for the segment 21q22.13-21q22.2 due to a de novo intrachromosomal duplication. A 500K SNP microarray analysis was then performed and revealed a 13-Mb duplication of 21q22.11-qter. This duplicated material had been translocated onto the end of the "p" arm of one of the chromosome 21s. The karyotype was provisionally defined as 46,XX,add(21)(p12).ish der (21)t(21;21)(p12;q22.11)(WCP21q+,PCP21q++,D215259/D21S341/D21S342++)dn. At the age of 4 years and 10 months, a comprehensive psychological examination was performed and the diagnostic criteria for mental retardation were not fulfilled. In comparison with previously published cases of pure partial trisomy 21, this is a rare finding. Additional studies of such rare patients should aid in the study of the pathogenesis of Down syndrome.

Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?

It is well known that varying degrees of mosaicism for Trisomy 21, primarily a combination of normal and Trisomy 21 cells within individual tissues, may exist in the human population. This involves both Trisomy 21 mosaicism occurring in the germ line and Trisomy 21 mosaicism documented in different somatic tissues, or indeed a combination of both in the same subjects. Information on the incidence of Trisomy 21 mosaicism in different tissue samples from people with clinical features of Down syndrome as well as in the general population is, however, still limited. One of the main reasons for this lack of detailed knowledge is the technological problem of its identification, where in particular low grade/cryptic Trisomy 21 mosaicism, i.e. occurring in less than 3-5% of the respective tissues, can only be ascertained by fluorescence in situ hybridization (FISH) methods on large cell populations from the different tissue samples.In this review we summarize current knowledge in this field with special reference to the question on the likely incidence of germinal and somatic Trisomy 21 mosaicism in the general population and its mechanisms of origin. We also highlight the reproductive and clinical implications of this type of aneuploidy mosaicism for individual carriers. We conclude that the risk of begetting a child with Trisomy 21 Down syndrome most likely is related to the incidence of Trisomy 21 cells in the germ line of any carrier parent. The clinical implications for individual carriers may likewise be dependent on the incidence of Trisomy 21 in the relevant somatic tissues. Remarkably, for example, there are indications that Trisomy 21 mosaicism will predispose carriers to conditions such as childhood leukemia and Alzheimer’s Disease but there is on the other hand a possibility that the risk of solid cancers may be substantially reduced.

Non‐chromosome 11‐p syndromes in Wilms tumor patients: Clinical and cytogenetic report of two Down syndrome cases and one Turner syndrome case

Non‐chromosome 11‐p syndromes in Wilms tumor patients: Clinical and cytogenetic report of two Down syndrome cases and one Turner syndrome case

Mitochondrial dysfunction and Down's syndrome.

Neither the pathogenesis nor the aetiology of Down's syndrome (DS) are clearly understood. Numerous studies have examined whether clinical features of DS are a consequence of specific chromosome 21 segments being triplicated. There is no evidence, however, that individual loci are responsible, or that the oxidative damage in DS could be solely explained by a gene dosage effect. Using astrocytes and neuronal cultures from DS fetuses, a recent paper shows that altered metabolism of the amyloid precursor protein and oxidative stress result from mitochondrial dysfunction.1 These findings are consistent with considerable data implicating the role of the mitochondrial genome in DS pathogenesis and aetiology.

An infant with Turner-Down aneuploidy and massive capillary hemangioma of the orbit: a case report with review

We report on a case of double aneuploidy involving Down and Turner cell lines in a female child with a massive capillary hemangioma of the left orbit and mild clinical features of Down syndrome. Cytogenetic findings with G-banding revealed mosaicism in her peripheral blood, i.e. mos45,X〚48〛/47,XX,+21〚28〛/46,XX〚12〛/47,XXX〚12〛. Mosaicism of such nature is rare and to our knowledge the present case is the first reported of Turner-Down double aneuploidy mosaicism associated with an orbital capillary hemangioma. An annotated bibliography of earlier reported cases with documented karyotyping is also included.

Functional genomics of Down syndrome: a multidisciplinary approach.

The availability of the DNA sequence of human chromosome 21 (HSA21) is a landmark contribution that will have an immediate impact on the study of the role of specific genes to Down syndrome (DS). Trisomy 21, full or partial, is a major cause of mental retardation and other phenotypic abnormalities, collectively known as Down syndrome (DS), a disorder affecting 1 in 700 births. The identification of genes on HSA21 and the elucidation of the function of the proteins encoded by these genes have been a major challenge for the human genome project and for research in DS. Over 100 of the estimated 300-500 genes of HSA21 have been identified, but the function of most remains largely unknown. It is believed that the overexpression of an unknown number of HSA21 genes is directly or indirectly responsible for the mental retardation and the other clinical features of DS. For this reason, HSA21 genes that are expressed in tissues affected in DS patients are of special interest.

DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways.

Down syndrome is one of the major causes of mental retardation and congenital heart malformations. Other common clinical features of Down syndrome include gastrointestinal anomalies, immune system defects and Alzheimer's disease pathological and neurochemical changes. The most likely consequence of the presence of three copies of chromosome 21 is the overexpression of its resident genes, a fact which must underlie the pathogenesis of the abnormalities that occur in Down syndrome. Here we show that DSCR1, the product of a chromosome 21 gene highly expressed in brain, heart and skeletal muscle, is overexpressed in the brain of Down syndrome fetuses, and interacts physically and functionally with calcineurin A, the catalytic subunit of the Ca(2+)/calmodulin-dependent protein phosphatase PP2B. The DSCR1 binding region in calcineurin A is located in the linker region between the calcineurin A catalytic domain and the calcineurin B binding domain, outside of other functional domains previously defined in calcineurin A. DSCR1 belongs to a family of evolutionarily conserved proteins with three members in humans: DSCR1, ZAKI-4 and DSCR1L2. We further demonstrate that overexpression of DSCR1 and ZAKI-4 inhibits calcineurin-dependent gene transcription through the inhibition of NF-AT translocation to the nucleus. Together, these results suggest that members of this newly described family of human proteins are endogenous regulators of calcineurin-mediated signaling pathways and as such, they may be involved in many physiological processes.

Overexpression of copper-zinc superoxide dismutase in trisomy 21.

Down's syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of chromosome 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain, where the occurrence of Alzheimer's disease is observed in trisomy 21 patients over the age of 35. Copper-zinc superoxide dismutase (CuZnSOD) is one of the proteins encoded by chromosome 21 (21q22.1). As a consequence of gene dosage excess, CuZnSOD activity is increased by 50% in all DS tissues. This work reports the SOD activity of a population of DS patients with complete trisomy 21, partial trisomy 21, translocations and mosaicism, in order to confirm the gene dosage effect of SOD on the clinical features of DS, and to help to establish which is the critical region of chromosome 21 in DS. CuZnSOD was measured in red blood cells using the Minami and Yoshikawa method. In the population with complete trisomy 21, SOD activity was increased by 42%; in the population with partial trisomy 21, translocations and mosaicism, SOD activity was normal. In the population diagnosed as DS, but not karyotyped, SOD activity was increased by 28%. No differences between sexes or among ages were found. We conclude that the 21q22.1 segment is not the critical region responsible for DS, as we have found normal SOD activity in patients with the clinical features of DS.