<unk>  is a genetic disorder caused by the presence of all or part of an extra 21st chromosome. Often<unk>  is associated with some impairment of cognitive ability and physical growth as well as facial appearance.<unk>  can be identified during pregnancy or at birth. John Langdon Down, a British doctor described it first in 1866. Jérôme Lejeune in 1959 ascribed the features associated with Down's syndrome to the presence of an extra 21st chromosome (trisomy 21). Based on anthropometric measurements and photographic appearance, John Landdon Down delineated a well-defined group of mentally disabled individuals, whose members all resembled the little girl very well. He called them, in concordance with the ethnical insights of the then famous dr. Blumenbach, mongoloid “idiots”. Today they are known by his own, more ethically correct name: Down's syndrome.<unk>  <unk>  is the consequence of trisomy of human chromosome 21 (Hsa21) and is the most common genetic form of intellectual disability. Additional copy of chromosome 21 results in elevated expression of many of the genes encoded on this chromosome, leading to variying expression of genes associated with this chromosome. Mechanisms leading to trisomy 21 include meiotic non-disjunction during meiosis I (majority) and meiosis II, Robertsonian translocation and mosaicism (rare). In addition, increased maternal age leads to rapid degradation of cellular proteins involved in spindle formation, sister chromatid cohesion and anaphase separation of sister chromatids in oocytes during cell cycle. Absence of chiasmata and suboptimally placed chiasmata are the major mechanisms involved in non-disjunction of chromosome 21.Immaturity of the feto-placental unit has been proposed as an explanation for the reduced maternal serum alpha fetoprotein (AFP) and unconjugated oestriol (UE3) levels and increased hCG levels in Down’s syndrome pregnancies. The diagnosis of<unk>  should be suspected in pre-natal assessment of fetuses on ultrasound examination. Second quad screen showing decreased alfa-fetoprotein (AFP) should raise the suspicion of fetal chromosomal abnormlaity. Pre-natal differentials of low AFP include<unk> , Edwards syndrome and Patau syndrome. In the newborn,<unk>  should be differentiated from other congenital conditions presenting with hypotonia, poor feeding, poor growth and dysmorphic facial features. The differentials include isolated hypotonia, congenital hypothyroidism and Zellweger syndrome.<unk>  is the most common chromosomal abnormality. Each year approximately 3,000 to 5,000 children are born with this chromosome disorder and it is believed there are about 250,000 families in the United States of America who are affected by<unk> . Birth rates are highest among mothers of advanced maternal age however 80% of all children with<unk>  are born to mothers younger than 35 years.<unk>  occurs in people of all races and economic levels. Common risk factors involved in the development of<unk>  include maternal smoking, increased maternal age, impaired recombination of chromosome 21, impaired folate metabolism and oral contraceptive pills (OCPs). Less common risk factors leading to the development of<unk>  include genomic instability in mothers, radiation exposure, low socioeconomic status and maternal obesity. During the first trimester of pregnancy, increased nuchal translucency in the fetus on ultrasound and decreased levels of pregnancy associated protein- A (PAPP-A) suggest the diagnosis of a chromosomal abnormality. Quad screen results during the second trimester of pregnancy may show increased beta-hCG, increased inhibin A, decreased alfa-fetoprotein (AFP) and decreased estriol. 3% of fetuses with Down’s syndrome diagnosed in utero at 16 weeks’ gestation would be lost spontaneously if termination of pregnancy was not performed. At birth, 50% of newborns with Down’s syndrome have one or more additional serious congenital abnormalities (in addition to intellectual disability). 96% without and 80% with heart defects survive the first year. At age 21 mean IQ is 42 (range 8–67) and mental age is 5 years (range 1–8 years). 11% develop Alzheimer’s disease by age 50 and 77% by age 70 (mean age of onset age 56). Common complication that may arise in patients suffering from<unk>  include, congenital heart defects (ASD, VSD, PDA), hearing loss, diabetes, celiac disease, cataracts, endocarditis, atlantoaxial subluxation, hypo and hyperthyroidism, duodenal atresia, Hirschprung disease. Life expectancy is 50–55 years.<unk>  is confirmed through cytogenetic studies which confirm trisomy 21. In addition complete blood count with differentials is performed to rule out leukemia, TSH and T4 are performed at birth, 6 months, 1 year and then annually to rule out hypothyroidism. Low level of IgG subclass 4 are correlated with bacterial infections. The mosaic trisomy 21 includes lymphocyte preparations, FISH, buccal mucosa cellular preparations and scoring frequency of trisomic cells. An x-ray may be helpful in the diagnosis of complications of<unk>  which include atrial septal defect, ventricular septal defect,atrioventricular septal defect, patent ductus arteriosus, 11 ribs, omphalocoele, mickey mouse pelvis, flaring of iliac wings, hyper-segmented sternum, joint laxity or dislocations, Developmental dysplasia of the hip, atlanto-axial subluxation, atlanto-occipital instability and hypoplastic posterior arch of C1. On X-ray of hands short hands with shortened phalanges and clinodactyly because of hypoplastic middle phalanx of the fifth finger can also be present. Treatment of individuals with<unk>  depends on the particular manifestations of the disease. For instance, individuals with congenital heart disease may need to undergo major corrective surgery soon after birth. Other individuals may have relatively minor health problems requiring no therapy. Patients suffering from<unk>  require rigorous follow-up in order to prevent the complications associated with the syndrome. Close monitoring of growth, hearing evaluation, ophthalmologic evaluation, thyroid profile, cardiac evaluation, dental care and close monitoring of complete blood counts in order to identify hematological maliganancies should be a part of care for a<unk>  patient.
Down syndrome
Apert syndrome
Lawrence-Moon syndrome
Williams syndrome
XX male syndrome
Goldstein-Hutt syndrome
Young Simpson syndrome
Hurler syndrome