International Journal of Health Sciences & Research (www.ijhsr.org) 497 Vol.6; Issue: 4; April 2016 International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571 Review Article Down’s Syndrome - Etiology and Mechanism Revisited Giriraj Kusre 1* , Priyanka Shankarishan 2** , Tulika Nirmolia 3** 1 Associate Professor, 2 Scientist-B, 3 Senior Research Fellow, * Department of Anatomy, Assam Medical College, Dibrugarh. ** CFDMGD Project, Department of Anatomy, Assam Medical College, Dibrugarh. Corresponding Author: Giriraj Kusre Received: 19/02/2016 Revised: 22/03/2016 Accepted: 28/03/2016 ABSTRACT Down’s syndrome is one of the commonest chromosomal disorders seen in human being. The most common cause of Down’s syndrome is the presence of an extra copy of chromosome 21. Non- disjunction is the most common mechanism for trisomy 21 and it occurs due to error in recombination during meiosis I and meiosis II stages. Although less common mechanism, the robertsonian translocation, isochromosome, mosaicism and partial translocation are also important contributors in the occurrence of down’s syndrome. Keywords: Down’s syndrome, non-disjunction, robertsonian translocation, isochromosome, mosaicism. INTRODUCTION Down’s syndrome (DS), the leading cause of congenital birth defects and mental retardation is the most common aneuploidy compatible with life, [1] occurring in about 1 out of 700 live births. [2] Although most common cause of DS is due to the presence of an extra copy of a complete chromosome 21 but over expression of few genes contained within 21q can also result in the same phenotype. [3] Trisomy 21 has a significant impact on the development of many tissues, most notably the heart and the brain. It is associated with a small number of conserved features, occurring in all individuals, including mild-to-moderate learning disability, craniofacial abnormalities and hypotonia in early infancy. The degree to which an individual is affected varies. Additionally, trisomy 21 is also associated with variant phenotypes that only affect some people with DS, such as atrioventricular septal defects (AVSDs) in the heart, acute mega-karyoblastic leukaemia (AMKL) and a decrease in the incidence of some solid tumours. [3,4] HUMAN CHROMOSOME 21: A BRIEF INTRODUCTION Human chromosome 21 is the smallest human auto some. The length of 21q is 38 Mb and approximately 3% of its sequence encodes for proteins. Chromosome 21 contains 225 genes and 59 pseudo genes. [5] Almost half of the chromosome 21 is a dark band when stained by Giemsa and such genes are known to be gene poor. The gene catalogue of chromosome 21 contains at least ten kinases, five genes involved in ubiquitination pathways, five for cell adhesion molecules, a number of transcription factors and seven ion channels. Exact gene responsible for the phenotype in DS has not yet been identified. [5] The complex phenotype that constitutes DS may in large part simply result from the over dosage of only one or a few genes within