Genetics 2 Genetic Disorders 6 Turner and Klinefelter Syndromes atf

hi everybody and welcome to our module on Klein felter and Turner syndromes Klein felter and Turner syndrome are sex chromosome anipo disorders this means these are genetic disorders where the affected individual has an abnormal number of sex chromosomes Klein felter syndrome occurs in males who have an extra X chromosome for example they may be xxy when they should be simply XY Turner syndrome occurs in females who are missing an X chromosome so instead of being XX they are referred to as x0 meaning they only have a single X chromosome both of these disorders can be

diagnosed by sending a patient for a test known as a karot type A carot type involves counting the number of chromosomes this is a picture of a kog shown in the screen here and in patients who have Klein felter or Turner syndrome you will either see an extra copy of the sex chromosomes or only a single copy of the X chromosomes and often multiple cells are analyzed for the numbers of chromosomes because as we will see some patients with these disorders display mosaicism meaning not all the cells in their body have abnormal numbers of sex

chromosomes let's start by talking about Klein felter syndrome in 80% of cases Klein felter syndrome occurs in boys who are 47xxy this means they have 47 chromosomes instead of the usual 46 they have X and Y just like normal boys should but then they have an extra X chromosome and this is usually the result of myotic non-disjunction of either parent I talk about how this occurs in the video on meiosis rarely these boys are 48 xxy meaning they have two extra X chromosomes these tend to be more severe cases because they have another X chromosome

in addition to the one extra that most cases of Klein felter Syndrome have and then sometimes boys with Klein felter syndrome display what's known as mosaicism which I talk about in other videos in mosaicism some cells in the body have different numbers of chromosome compared with others in this case some cells in the body are normal in other words they are 46xy with just one X and one Y chromosome whereas other cells are 47xxy and are abnormal these tend to be less severe cases because some cells in the body have the normal complement of sex

chromosomes and these cases of mosaicism are not due to meiosis errors they're usually due to mitosis errors they occur due to non-disjunction during mitosis after conception and the same thing is true in other genetic disorders where there is mosaicism this can occur in Down syndrome where mosaicism is due to mitosis errors and not myotic errors this is a cariogram of a patient with Klein felter syndrome you can see that there are two copies of all the numbered chromosomes and then there are also two copies of the X chromosome and one copy of the Y chromosome

thus this patient has 47 chromosomes and three sex chromosomes with an extra X an easy way to remember the features of Klein felter syndrome is to think of it as a feminized male the patients who have this disorder have an X and A Y chromosome so so they are male in appearance however because of the extra X chromosome they have many female features so one of these features is that they are going to display hypogonadism their testes are going to be underactive because of that extra X chromosome they have small firm testes they have atrophy

of the seminiferous tubules they typically have low testosterone levels and we'll talk more about this in a minute and it is the ratio of estrogens to testosterones that determines the disease severity individuals that have two extra X chromosomes have lots of estrogens relative to testosterone and they have more severity of their disorder because the testes are hypoactive the levels of gatot tropins coming from the pituitary gland will increase so there will be low levels of inhibit B coming from the testes this will lead to high levels of FSH from the pituitary there will be low

testosterone from the testes this will lead to high levels of LH coming from the pituitary here's a slide from our Endocrinology video on male reproductive hormones just to remind you that in the testes you can find litic cells and CI cells and they make testosterone and inhibin which feed back negatively on the pituitary gland so incline felter syndrome when you have lower levels of testosterone and lower levels of inhibin because the testes are underactive this leads to loss of negative feedback and thus the levels of LH and FSH can rise low testosterone and relative excess

of estrogen account for many of the clinical features of Klein felter syndrome boys with this disorder display delayed puberty and in fact this disorder is often first diagnosed at puberty because prior to that point the children will appear to be a normal male these boys have reduced facial and body hair they often have a female pubic hair pattern as is shown in this picture on the screen here they can develop gynecomastia and in addition they often have infertility and reduced sperm counts genital anomalies are common in boys with Klein felter syndrome first of all they

often have Crypt orchidism which is undescended testes in addition they often have hypospadia hypospadia is where the opening of the urethra is not in the normal position at the head of the penis shown on the screen are a couple examples of different types of hypospadia and then finally boys with Klein felter syndrome often have a very small penis this is called micro penis patients with Klein felter Syndrome have a characteristic physical appearance first of all they usually have long legs and long arms if you look at this picture on the screen this is a picture

of a man with Klein felter syndrome you can see that he is tall because he has long legs and he also has long arms and this happens to clein felter patients because they have an extra copy of a gene called the shocks Gene found on the X chromosome and this Gene is important for long bone growth patients with Klein felter are also said to have what's known as a unid body shape a unid body shape means a body shape that is lacking in sexual differentiation between male and female it's sort of an in between body

shape and you can see that if you look at this man on the screen here he's lacking the usual broad shoulders that men have and he's got a body shape that is sort of in between the male and female body shape patients with kleinfelter syndrome can display cognitive findings they sometimes have learning disabilities like delayed speech and language development they also often have a quiet personality meaning that they are relatively quiet individuals and not very assertive for the USM step one exam it's high yield to know that patients with Klein felter syndrome can have a

bar body found in the nucleus of their cells a bar body is an inactivated X chromosome it's normally found only in the cells of females females are XX so one of their X chromosomes undergoes a process called lionization where that X chromosome becomes condensed into heterochromatin with methylated DNA and thus it becomes inactive so that in each cell of a female's body Only One X chromosome is active the other one is inactive and appears as a bar body which I've shown on the screen here it's a dark spot at the periphery of the nucleus and

it indicates an inactive X chromosome in patients with Klein felter syndrome you can also see a bar body and normally you do not see this males but you will see it in males who have Klein felter syndrome because they have that extra X chromosome in contrast to Klein felter syndrome in Turner syndrome there is a missing sex chromosome 45% of cases occur in girls who are 45x this means they have 45 chromosomes instead of the usual 46 and they only have a single sex chromosome an X chromosome they are missing the second copy of their

X chromosome most of these cases are caused by fertilization of an egg with a sperm that lacks the X chromosome many cases of Turner syndrome are what's known as Mosaic Turner syndrome these are often milder cases in these cases girls are born with a mosaic of chromosomes in their body so some cells will be 45x but other cells will be normal and will be 46xx this version of Turner syndrome Mosaic Turner syndrome is caused by mitotic non-disjunction during the postotic cell division stage and this is common to many genetic disorders Mosaic down syndrome is caused

by mitotic non-disjunction Mosaic Klein felter syndrome is caused by mitotic non-disjunction and so is Mosaic Turner syndrome we saw before that Klein felter syndrome is a male who is very tall in contrast Turner syndrome will be a female who is very short and this is because girls with Turner Syndrome have lost one copy of that shocks gene on the X chromosome we mentioned earlier and because females with turner syndrome are often short they are often administered growth hormone in childhood to try to have them de develop to a normal height other classic features of Turner

syndrome include a broad chest this is sometimes described as a shield chest because the chest looks sort of square like a shield would in medieval times and in addition they often have widely spaced nipples so they'll have the shield chest with the nipples very far apart on the chest there are a couple of features of Turner syndrome that are believed to result from lymphatic obstruction that occurs during fetal development girls with Turner Syndrome classically have a webbed neck as shown in this picture on the right side of the the screen this is believed to result

from poor lymphatic flow during fetal development in addition babies with turner syndrome often have swollen hands and feet especially right at the time of birth some girls with Turner Syndrome have an anomaly called a cystic hygroma This Is A congenital lymphatic defect there's a picture of one shown in this child on the screen here it's a large collection of lymph and cyst that's why it's called a cystic Hy groma it's often found in the head and neck and it is sometimes detected in utero on fetal ultrasound ovarian function is typically abnormal in girls with turner

syndrome the Hallmark of the disorder is a female with primary hypogonadism these girls have loss of ovarian function it's often described as gonadal dis Genesis in addition a classic finding is what's known as streak ovaries this is where there are streaks of fibrous tissue seen in the expected location of the ovaries and these girls have no or very few follicles shown on the screen is a picture of the ovary it's normally found in the middle of the broad ligament but in girls with syndrome instead of ovarian tissue there will be streaks of fibrous tissue hence

the name streak ovaries because the ovaries are abnormal there are decreased levels of inhibit B and estrogens to feed back on the pituitary gland and therefore you can see increased levels of LH and FSH just like we talked about in Klein felter syndrome in actual practice it turns out that the levels of LH and FSH vary during childhood they are sometimes normal during certain periods of development therefore you can't rely on these for diagnosis they're often most abnormal in early childhood and pre-puberty after 10 years of age if this disorder isn't picked up early because

of presence of a webbed neck or puffy feet or a cystic hyoma it's often diagnosed at the time of puberty girls with turner syndrome will display delayed puberty they will have absence of breast development and failure to menstrate this is sometimes treated with estrogen supplementation to try and induce normal changes of puberty in girls who have this disorder in addition Turner syndrome typically leads to primary amenorrhea in fact is the most common cause this is sometimes referred to in textbooks as menopause before menarchy basically these girls are born with insufficient ovarian tissue so they have

menopause before they've had the start of menes now some girls will menstrate and develop menopause early in their teens or 20s these are usually girls with the milder form the Mosaic form of Turner syndrome most women with turner syndrome are infertile as I mentioned before they are born with zero or relatively few ovarian follicles some women can become pregnant if they use donated oo sites because they can carry the baby to term once the egg has been fertilized it's very high yield for step one to know the cardiovascular complications of Turner syndrome which I listed

on this slide about a third of girls born with Turner Syndrome have a bicuspid aortic valve normally the aori valve has three cusps but in about 30% of girls with turner syndrome it has two cusps as shown in this picture on the screen up to 10% of girls with Turner Syndrome have coarctation of the aorta as shown in this picture here I discussed this in detail in the Cardiology section in the video on congenital heart defects and then finally high blood pressure is common in girls with turner syndrome it may even occur in childhood it

is sometimes due to the coration of the order or renal disease which we'll talk about in a minute however it's often a primary disorder kidney malformations affect about a third of children with turner syndrome often it is an abnormality of the collecting ducts however children with turner syndrome can also develop a horseshoe kidney which is something they like to test on step one of the boards this is a horseshoe kidney shown on the screen here the lower poles of both kidneys are fused and for this reason the fused horseshoe kidney sits lower in the pelvis

I talk about horseshoe kidney in the renal section in the video on embryology there's a high incidence of osteoporosis in women with turner syndrome this is because there are low levels of circulating estrogens because of the single X chromosome and for this reason estrogen treatments are often prescribed in order to increase the bone density and then finally women with turner syndrome often have endocrine disorders type 2 diabetes is more common than in the general population and about a third of women with Turner Syndrome have some form of thyroid disease it's usually hypothyroidism from Hashimoto's thyroiditis

and that concludes our video on Klein felter and Turner syndromes