Klinefelter (XXY) and Turner Syndrome (Gonadal Dysgenesis)

00:01 In this lecture, we will discuss Klinefelter Syndrome and Turner Syndrome.

00:06 These are genetic problems with the sex chromosomes.

00:09 So let?s start with Klinefelter Syndrome.

00:12 These patients usually have male hypogonadism.

00:15 They have 2 or more X chromosomes and 1 or more Y chromosomes.

00:20 Most commonly, two X?s and one Y like you can see in this patient?s karyotype.

00:25 This occurs in 1 out of 650 live births.

00:29 So, it?s not that uncommon.

00:30 This is generally due to maternal or paternal nondisjunction during meiosis as they?re making either the sperm or the egg.

00:38 There?s a slightly increased risk of this happening in mothers who are of advanced maternal age.

00:46 Sometimes, Klinefelter Syndrome patients are fertile and can go on to have their own children.

00:54 Fertile Klinefelter Syndrome patients have a low reccurence of Klinefelter Syndrome in their offspring, but the offspring do carry a very small increased risk of chromosomal abnormalities.

01:06 So let?s review the clinical features of Klinefelter Syndrome.

01:11 They often suffer infertility.

01:14 They may have hypogonadism with small testes.

01:18 They often have gynecomastia in adolescence as a result of an imbalance between testosterone and estrogens.

01:26 You?ll notice they have reduced body hair.

01:29 They will be tall and have a ?pear shaped? stature to them and they occasionally have educational and psychological problems.

01:39 So how do we diagnose Klinefelter Syndrome if we suspect the patient might have it? Well first, we?ll send a karyotype or an array comparative genomic hybridization.

01:51 This will make our definitive diagnosis.

01:53 We will also screen these patients when they are adult males for infertility.

01:58 That?s useful for them to know about for often they a decreased sperm count.

02:03 It?s important to check their testosterone levels.

02:06 They will often have a decreased testosterone in the phase of hypergonadotropism.

02:12 In other words, they have hypergonadotropic hypergonadism.

02:17 Their testes are nonresponsive to LH and FSH, so they have high LH and FSH hormone levels.

02:25 So how do we improve these patients? lives? The first thing that?s very important is that they should receive testosterone therapy.

02:35 This will help a number of things especially their facial and body hair issues.

02:40 It will improve their strength and muscle size.

02:42 It will improve their energy level. It will help them with libido issues.

02:46 It will help them with confidence and it will help them with concentration.

02:51 So we often will refer these patients to reproductive specialists or infertility specialists as well to help them with various reproductive options if they should decide to have a child.

03:03 So let?s focus now on Turner Syndrome.

03:06 Turner Syndrome is a partial or a complete monosomy of the X chromosome.

03:12 This results in hypogonadism in the phenotypic female.

03:17 The incidence is about 1 in 2,000 live births.

03:21 So how does this happen? Well, more than 60% are due to do novo meiotic nondisjunction in the paternal sex chromosomes.

03:32 So the dad has an X and a Y and instead of splitting into one X and one Y sperm is basically an XY sperm and an empty sperm and the empty sperm now then goes and fertilizes the egg creating a single X chromosome.

03:47 Turner Syndrome occurs essentially only in females.

03:51 Males can be mosaic for Turner Syndrome.

03:56 This is rare but it can happen where a male has some cells that are 45, X and other cells that are 46, XY.

04:05 So what are the symptoms in females of Turner Syndrome? These are important to remember.

04:12 These patients will have a delayed puberty.

04:15 They will often have amenorrhea. This is from gonadal dysfunction.

04:20 They may have premature ovarian failure.

04:23 This results in infertility and some patients may have some learning disabilities especially in Math but generally, these patients are cognitively normal.

04:35 Patients with Turner Syndrome may have short stature.

04:40 In fact, they almost always do.

04:41 They have low set ears, a low hairline and you may notice a webbed neck or a broadened neck root.

04:49 Additionally, you can see small jaw, a ?shield chest? which is a broadened or a widened chest often with widely spaced nipples.

04:59 You may see cubitus valgus or outward-turned forearms.

05:04 They may have a horseshoe kidney internally which they may not even know about and they can develop congenital heart disease.

05:11 So how do we test and when do we test for Turner Syndrome? You should consider attempting prenatal diagnosis if the fetal ultrasound shows intrauterine growth restriction, fetal edema, a coarctation of the aorta or cystic hygroma.

05:30 In this case, if a parent wishes to do a prenatal testing, we generally do chorionic villi sampling or amniocentesis with karyotype.

05:39 Postnatally, the diagnosis is made by karyotype or aCGH just like in Klinefelter Syndrome.

05:48 So what therapy do we provide these patients? After initially making the diagnosis, we will screen them generally with an echocardiogram or a renal ultrasound especially paying attention to any abnormalities of the heart such as aortic problems or if there?s an abnormal kidney.

06:09 Additionally, we will typically check them for their thyroid function.

06:13 We?ll do an eye exam and we will assess for scoliosis which is a little bit more common in these patients.

06:19 It?s important to refer these patients to a pediatric endocrinologist for hormonal replacement.

06:25 These patients will receive estrogen, progestin and growth hormone.

06:30 If you look at this picture, here are two patients with Turner Syndrome.

06:35 The one on the left received no growth hormone and the one on the right received growth hormone.

06:42 Growth hormone is indicated in these patients and can really help them in terms of achieving an important stature.

06:48 The reason why we give it is because for patients who don?t achieve 5 feet of height, this can result in significant impairment and their ability to function in the world and may be simply hard for them to drive a car.

07:01 We want these patients to live the most fulfilled life that they can.

07:05 It?s also important to refer these patients to fertility specialists for consideration of their reproductive options when they enter into adulthood.

07:14 So that?s my review of Turner Syndrome and Klinefelter Syndrome.

07:18 Thanks for your time.