Down Syndrome is one of most common causes of mental retardation. It also causes physical abnormalities and tendency to infections therefore pediatricians are commonly involved in the care of these children. Another important point about this syndrome is that it is the most common chromosomal disorder.
Prevelance is 1/700 live birth and 10% of all mentally retarded children have Down Syndrome. Improved care increased the survival of these children and they can live longer and reach to middle age. Ethiology is trisomy of the chromosome 21( 3 copies of chromosome number 21).
Most common form is free trisomy 21 but it could also be translocated to another acrocentric chromosome. There is no phenotypical difference between translocation and free trisomy cases.

It is first fetected by Edwards and colleges in a newborn in 1960’s. Incidance is 1:3000-1:8000 liveborn child. It is the second most common trisomy syndrome after Down syndrome.
Trisomy 18 and trisomy 13 babies usually have low birth weight, born with one umbilical artery. In trisomy 18, placenta is small and hydramnios is common. They usually die of apnea or cardiac insufficiency.
Trisomy 13 is described by Patau and collegues in 1960’s. These children are usually diagnosed by severe congenital anomalies in neonatal period. They are mostly lost before 6 month of age.
Turner syndrome (TS) is a panethnic disorder caused by complete or partial absence of a second X chromosome in females. It has an incidence of between 1 in 2000 and 1 in 5000 liveborn girls. About 50% of TS cases are associated with a 45,X karyotype, 25% with a structural abnormality of the second X chromosome, and 25% with 45,X mosaicism (see Chapter 6). Monosomy for the X chromosome can arise either by the failure to transmit a sex chromosome to one of the gametes or by loss of a sex chromosome from the zygote or early embryo. Failure to transmit a paternal sex chromosome to a gamete is the most common cause of a 45,X karyotype; 70% to 80% of patients with a 45,X karyotype are conceived from a sperm lacking a sex chromosome. Loss of a sex chromosome from a cell in the early embryo is the likely cause of 45,X mosaicism.
The mechanism by which X chromosome monosomy causes TS in girls is poorly understood. The X chromosome contains many loci that do not undergo X chromosome inactivation (see Chapter 6), several of which appear to be necessary for ovarian maintenance and female fertility. Although oocyte development requires only a single X chromosome, oocyte maintenance requires two X chromosomes. In the absence of a second X chromosome, therefore, oocytes in fetuses and neonates with TS degenerate, and their ovaries atrophy into streaks of fibrous tissue. The genetic bases for the other features of TS, such as the cystic hygroma, lymphedema, broad chest, cardiac anomalies, renal anomalies, and sensorineural hearing deficit, have not been defined but presumably reflect haploinsufficiency for one or more X-linked genes that do not normally undergo inactivation in the female.
Phenotype and Natural History
Although 45,X conceptuses account for between 1% and 2% of all pregnancies, less than 1% of 45,X conceptions result in a liveborn infant. In view of the mild phenotype observed in patients with TS, this high rate of miscarriage is remarkable and suggests that a second sex chromosome is generally required for intrauterine survival.
All patients with TS have short stature, and more than 90% have ovarian dysgenesis. The ovarian dysgenesis is sufficiently severe that only 10% to 20% of patients have spontaneous pubertal development (breast budding and pubic hair growth) and only 2% to 5% have spontaneous menses. Many individuals also have physical anomalies, such as webbed neck, low nuchal hairline, broad chest, cardiac anomalies, renal anomalies, sensorineural hearing deficit, edema of the hands and feet, and dysplastic nails. Nearly 50% of patients have a bicuspid aortic valve and therefore an increased risk of aortic root dilatation and dissection; nearly 60% have renal anomalies and an increased risk of renal dysfunction.
Most patients have normal intellectual development. Those with intellectual impairment usually have an X chromosome structural abnormality. Socially, individuals with TS tend to be shy and withdrawn (see Chapter 6).
In addition to the complications resulting from their congenital anomalies, women with TS have an increased incidence of osteoporotic fractures, thyroiditis, diabetes mellitus type 1 and type 2, inflammatory bowel disease, and cardiovascular disease. The causes of the diabetes mellitus, thyroid disorders, and inflammatory bowel disease are unclear. Estrogen deficiency is probably largely responsible for the osteoporosis and the increased incidence of atherosclerosis, ischemic heart disease, and stroke, although diabetes mellitus probably accentuates the cardiovascular effects of estrogen deficiency.
When a TS patient's stature falls below the fifth percentile, she is usually treated with GH supplements until her bone age reaches 15 years (Fig. C-42). On average, this treatment results in a gain of 10 cm in predicted height; the improvement in final height is less, however, the later GH therapy is started. Concurrent estrogen therapy decreases the effectiveness of GH.
Estrogen therapy is usually initiated at about 14 to 15 years of age to promote development of secondary sexual characteristics and reduce the risk of osteoporosis. Progesterone therapy is added to the regimen to induce menses either at the time of the first vaginal breakthrough bleeding or in the second year of estrogen therapy.
In addition, medical management usually includes echocardiography to evaluate aortic root dilatation and valvular heart disease, renal ultrasonography to find congenital renal anomalies, and a glucose tolerance test to detect diabetes.
Patients who have complete ovarian dysgenesis do not ovulate spontaneously or conceive children. If they have adequate cardiovascular and renal function, however, women with TS can have children by in vitro fertilization and ovum donation.
Inheritance risk
TS is not associated with advanced maternal or paternal age. Although there have been a few familial recurrences, TS is usually sporadic, and the empirical recurrence risk for future pregnancies is not increased above that of the general population. If TS is suspected on the basis of fetal ultrasound findings, such as a cystic hygroma, the diagnosis should be confirmed by karyotyping of chorionic villi or amniocytes.
Only a few pregnancies have been reported among spontaneously menstruating patients with TS. Among the resulting offspring, one in three has had congenital anomalies, such as congenital heart disease, Down syndrome, and spina bifida. The apparently increased risk of congenital anomalies may be due to ascertainment bias in reporting, since pregnancy is unusual in TS. If the increased risk is a real finding, the cause is unknown.
It is the first described sex chromosome abnormality in human. Incidance is 1:1000 ive male birth. It is described in 1942 by Klinefelter as testicular dysgenesis,high gonadotrophin levels in urine and gynecomastia. 80% to 90% of these patients have 47,XXY karyotype. Other structural abnormalities [47,X,i(Xq),Y ; 47X,del(X),Y ] are rare forms. These forms have one normal and one abnormal X. 10% of Klinefelter syndrome cases have various mosaic forms and most common one is: 46,XY/47,XXY
Other mosaics are the following :
In the mosaic forms with XY chromosomes, have milder phenotype and some of them are fertile. Infertility is usually the first sign and reason for diagnosis. They are typically of normal intelligence or have mildly low IQ levels. They look normal until puberty when the signs of hypogonadism can be noticed . Puberty is usually achieved on time but testicles are small and secondary sexual characters are underdeveloped and gynecomastia is common. Psychosexual behaviour is usually male oriented.
Theses syndromes are caused by small deletions/duplications along certain parts of some chromosomes. The resulting phenotype is the outcome of the missing genes along the deleted chromosomal segment, therefore named as ‘contigious gene syndromes’. Other deletion syndromes are usually the result one missing gene, causing one single phenotype. These syndromes resulting from unequal recombination can be diagnosed by FISH or molecular analysis. The following are most common examples of Microdeletion/Microduplication Syndromes:




Smith Magenis Syndrome



Prader Willi/ Angelman Syndroem



Williams Syndrome



DiGeorge Syndrome