Down syndrome and consanguinity

Clinical Genetics, 2008

In order to reveal if there is an effect on the genesis of meiotic-or early zygotic non-disjunctions, data related to 1598 Down syndrome patients from 1578 families studied in five different genetic centers in Turkey are reported. Parental consanguinity and the inbreeding coefficient were found to be lower among patients of 21-trisomics than in parents without Down offspring. It was concluded that available information does not support the presence of a "non-disjunction gene" in man. 'Ankara University Medical Faculty, Ankara; 'Ege University Medical Faarlty, izmir; and Departments of 'Medical B i i. and 'Biostatistics. Ana

Human Genetics, 1985

The existence of a rare autosomal gene which in the homozygous state would cause mitotic nondisjunction in the Down zygote has been hypothesized in the past by . This hypothesis can be supported or contradicted by the study of the frequency of consanguineous marriages among parents of affected children. Our study on 242 children affected with Down syndrome does not show any increase in the frequency of consanguineous marriages among their parents with respect to the general population, and therefore does not support the hypothesis of an autosomal gene controlling mitotic nondisjunction. Our data do not show any increase in the frequency of consanguineous marriages even among paternal and maternal grandparents of the affected children, thus not supporting the other possible explanation of an autosomal recessive condition in one of the patient's parents which would cause meiotic nondisjunction.

American Journal of Scientific and Industrial Research, 2010

Objective of our study was to ascertain the relation of consanguinity to Down syndrome (DS), and pattern of congenital heart defects (CHD) in DS. Setting: Department of Pediatrics, G B Pant Hospital, an associated hospital of Govt Medical College Srinagar. It was designed as a case control study. Fifty phenotypically DS patients aged between 0-12 years, attended our hospital from September 2007 to August 2008, were selected, formed the cases (Group I), and an equal number of patients, comparable in all respects but without DS or other apparent congenital malformations, were kept as controls (Group II). After detailed history and thorough examination, patients were enquired about the familial ties, and traditional values and a three generation pedigree was generated to ascertain consanguinity. All patients underwent echocardiography in addition to routine laboratory tests. The chi-square test was used to compare the proportions. Males constituted 27 and 26, while as females constituted 23 and 24 in group I and II respectively (p-value=0.841). Frequency of CHD among group I and II was 25(50%) and 15 (30%) respectively (p-value=0.041, OR=2.3). Pattern of CHD showed atrio-ventricular canal defects (AV canal defects) in 7 (28%) in group I, and nil among group II (p-value=0.024, OR=11.7), while as the commonest CHD in both groups was VSD. Among the group I consanguinity was present in 14 (28%), while in group II consanguinity was present 17 (34%) (p-value=0.51, OR=0.75). However, in group I with CHD, consanguinity was observed in 14 (56%), and in group II with CHD consanguinity was observed in 3(20%) patients (p-value 0.001, OR 9.3). Fifteen (60%) cases among the group I and 4 (26.7%) cases among the group II were females with CHD (p-value=0.041, OR=4.1).CHD is more common and severe among DS children who are products of consanguineous marriage, and CHD is more frequently seen in female DS children.

Genetic Testing and Molecular Biomarkers, 2012

The aims of the present study were to assess (1) the parental origin of trisomy 21 and the stage in which nondisjunction occurs and (2) the relationship between altered genetic recombination and maternal age as risk factors for trisomy 21. The study included 102 cases with Down syndrome from the Croatian population. Genotyping analyses were performed by polymerase chain reaction using 11 short tandem repeat markers along chromosome 21q. The vast majority of trisomy 21 was of maternal origin (93%), followed by paternal (5%) and mitotic origin (2%). The frequencies of maternal meiotic I (MI) and meiotic II errors were 86% and 14%, respectively. The highest proportion of cases with zero recombination was observed among those with maternal MI derived trisomy 21. A higher proportion of telomeric exchanges were presented in cases with maternal MI errors and cases with young mothers, although these findings were not statistically significant. The present study is the first report examining parental origin and altered genetic recombination as a risk factor for trisomy 21 in a Croatian population. The results support that trisomy 21 has a universal genetic etiology across different human populations.

International Journal of Anatomy and Research, 2017

Back ground: Consanguinity (CON) is defined as marriage between the close relatives and strongly favoured among the Populations of South India and plays an important role in the high incidence of congenital malformations in children, due to Expression of rare recessive genes inherited from a a common ancestor. Aims: The present study is undertaken to analyze the effects of CON on congenital malformation and associated chromosomal abnormalities Methods and Material: A total of 550 cases with suspected genetic etiology were referred to Division of Cytogenetics, Department of Anatomy SSMC, Tumakuru, Karnataka since 2 years. Karyotyping was done from peripheral blood lymphocyte culture and G-T-G Banding using trypsin and Giemsa. Karyotype descriptions were reported and findings were statistically analyzed and those patients with chromosomal abnormalities received post Cytogenetic Genetic counselling in our Department. Results: CON marriages were represented in 36% of cases. Stillbirths, recurrent abortion, and congenital anomalies were significantly increased. Chromosomal anomalies were grouped as structural and numerical anomalies and highest frequency of abnormal karyotype was found among cases of Down's syndrome and repeated abortion. Conclusions: The present study is undertaken to analyze the effects of CON on Genetic disorders and associated chromosomal abnormalities which demonstrate the importance of cytogenetic evaluation, public health education, and genetic counseling.

Medical Archives, 2015

Background: Advanced paternal and/or maternal age is a classic risk factor for Down syndrome. The aim of the study was to investigate the frequency of Down syndrome types in children and its association with maternal and paternal age in Bosnia and Herzegovina. Subjects and Methods: The cross sectional, observational study included 127 children, 49 girls and 78 boys, aged 1-180 months suspected to have Down syndrome, admitted to the Centre for Genetics, Faculty of Medicine University of Sarajevo, for cytogenetic analysis and differential diagnosis of Down syndrome during the period from January 2010 to May 2015. Standard method of 72 hours cultivation of peripheral blood lymphocytes has been applied. The accepted level of statistical significance was p<0.05. Study Results: The most common type of Down syndrome was standard trisomy (86.6%), comparing to translocation and mosaicism (7.1%; 6.3%, respectively). The highest frequency of Down syndrome cases was in mother and father's group from 30-39 years old (57; 57 children, respectively) compared to mother and father's groups with younger than 30 (44; 29, respectively) and 40 and older (26; 41, respectively). The significant difference was found in maternal age between translocation and mosaicism groups (p=0.036). Difference between parental years and type of Down syndrome was significant when Standard trisomy 21 and translocation (p=0.045), as well as mosaicism and translocation (p=0.036), were compared. Conclusion: The most common type of Down syndrome was standard trisomy 21, with highest occurrence in parents from 30 to 39 years old. Parents were the youngest in translocation group. Obtained results suggest that multidisciplinary approach to identifying the trigger for trisomy appearance and the influence of maternal age is required.

2021

Background Parental consanguinity affects the pattern of congenital heart defects (CHDs). The association between Down's syndrome (DS) and congenital heart defects has long been known. Parental consanguinity may affect the pattern of CHDs. Some communities in Afghanistan have a high consanguineous marriage rate, possible affecting the types of CHDs in children with DS. Objective To determine the frequency and distribution of CHDs in children with Down's syndrome in Afghanistan, where the community had a high consanguineous marriage rate. Methods This prospective cross-sectional study was conducted in Maiwand Hospital, a pediatric teaching hospital in Kabul, Afghanistan. Subjects were children with DS shown by clinical and cytogenetic studies, and referred to the Pediatric Cardiology Service from September 2018-September 2020. Parental consanguinity was documented. Subjects underwent 2D echocardiography and Doppler studies performed by two experienced pediatric cardiologists after physical examination, ECG, and chest X-ray. Results During the two-year study period, 120 DS patients were identified, 78 (65%) of whom had CHDs. The prevalences of isolated and multiple CHD in the 78 children with DS were 35.8% (43 patients) and 29.1% (35 patients), respectively. The most common isolated defects were ventricular septal defect (21.7%) and atrial septal defect (15.3%). The most common CHD associations were VSD + PDA (20.5%) and VSD + ASD (10.2%). Consanguinity was found in 69.2% of all parents. Conclusion A higher frequency of CHD is documented in DS children from parents with a high consanguineous marriage rate. The frequencies of specific lesions are similar to those reported locally and internationally; VSD is the most frequently detected in our study. The predominance of left-right shunt lesions and the relative rarity of cyanotic and complex CHD are notable in this DS population.

INTERNATIONAL JOURNAL OF HUMAN GENETICS

Down syndrome is mainly numerical change of chromosome 21 which is found 1 per 1200 live births in India. Chromosomal analysis is necessary for primary diagnosis. Socioeconomic factor may affect indirectly in case of Down syndrome patient. Previous miscarriage of mother is related with the next birth of Down syndrome baby. After screening 218 genetically abnormal cases, 45 cases were diagnosed as Down syndrome, in Genetics Department of Ramakrishna Mission Seva Pratishthan. Detailed clinical and socio-economical history and anthropometric measurement were taken from these particular patients. Maximum cases of Down syndrome are from Socioeconomically deprived area. Stunting growth is found in Down syndrome cases. 75.56% mothers have previous reproductive wastage.

BMC medical genetics, 2006

Down syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92-95%), mosaic trisomy 21 (2-4%) and translocation (3-4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction. We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression. Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was g...

2008

Down syndrome or trisomy 21 can be caused by three types of chromosomal abnormalities: free trisomy 21, translocation or mosaicism. The cytogenetic diagnosis, made through karyotypic examination, is important mainly to determine recurrence risks to assist genetic counselling. The object of this work was to carry out a cytogenetic profile of confirmed cases of Down syndrome seen in the General Genetics Outpatient Service in a teaching hospital -Hospital de Base in São José do Rio Preto -from the implementation of the service in 1973 to November 2005, with the purpose of establishing the nature of the cytogenetic abnormalities of these patients. A retrospective study was performed, in which the karyotypes of patients with Down syndrome consulted at the General Genetics Outpatient Service of HB-FAMERP from 1973 to November 2005 were investigated. The results of cytogenetic analysis were obtained from the consultation register and patients' hospital records. The results show 387 Down syndrome cases confirmed by karyotypic examinations. Of these, 357 (92.2%) patients had free trisomy of chromosome 21, 24 (6.2%) had translocation involving chromosome 21 and 6 (1.5%) had mosaicism. Nondisjunction was the main cause of Down syndrome, as the majority of the patients have free trisomy of chromosome 21. The cytogenetic pattern of Down syndrome is variable among different studies.