Turners syndrome

Question 1

What is Turner’s syndrome?

Answer 1

Turner’s syndrome is a chromosomal disorder affecting about 1 in 2,500 females, characterized by the presence of only one X chromosome or a deletion on one of the X chromosomes.

Question 2

How is Turner’s syndrome denoted genetically?

Answer 2

Turner’s syndrome is genetically denoted as 45,XO or 45,X.

Question 3

What are common physical features of Turner’s syndrome?

Answer 3

Common features include short stature, shield chest, widely spaced nipples, webbed neck, and a high-arched palate.

Question 4

What are some common cardiovascular issues in Turner’s syndrome?

Answer 4

Cardiovascular issues include a bicuspid aortic valve (15%) and coarctation of the aorta (5-10%).

Question 5

What are the most serious long-term health problems for women with Turner’s syndrome?

Answer 5

The most serious long-term health problems are an increased risk of aortic dilatation and dissection.

Question 6

Why is regular monitoring important in adults with Turner’s syndrome?

Answer 6

Regular monitoring is important to check for serious complications like aortic dilatation and dissection.

Question 7

What is primary amenorrhoea in the context of Turner’s syndrome?

Answer 7

Primary amenorrhoea refers to the absence of menstruation due to Turner’s syndrome.

Question 8

What is a common prenatal diagnosis associated with Turner’s syndrome?

Answer 8

Cystic hygroma is often diagnosed prenatally in Turner’s syndrome.

Question 9

What skeletal feature is notably short in Turner’s syndrome?

Answer 9

Individuals with Turner’s syndrome often have a short fourth metacarpal.

Question 10

What is the most common renal abnormality in Turner’s syndrome?

Answer 10

The most common renal abnormality in Turner’s syndrome is a horseshoe kidney.

Question 11

What is the relationship between Turner’s syndrome and autoimmune diseases?

Answer 11

There is an increased incidence of autoimmune diseases, especially autoimmune thyroiditis and Crohn’s disease, in individuals with Turner’s syndrome.

Question 12

How are gonadotrophin levels affected in Turner’s syndrome?

Answer 12

Gonadotrophin levels are elevated in individuals with Turner’s syndrome.

Question 13

How common is hypothyroidism in Turner’s syndrome?

Answer 13

Hypothyroidism is much more common in individuals with Turner’s syndrome.

Question 14

What is lymphoedema and how is it related to Turner’s syndrome?

Answer 14

Lymphoedema, particularly in the feet of neonates, is a common condition associated with Turner’s syndrome.

Question 15

What are multiple pigmented naevi in the context of Turner’s syndrome?

Answer 15

Multiple pigmented naevi, which are numerous skin moles, are a common feature in individuals with Turner’s syndrome.

Question 16

A 16-year-old girl attends your GP surgery due to concerns about delayed menarche. On history, you note that there have been no developmental concerns. She is at the 65th percentile for weight and 5th percentile for height. On examination, you note that she has a short webbed neck and a broad chest. You perform karyotype analysis, which is abnormal. What is the most common cardiac condition associated with this presentation?

Bicuspid aortic valve
Patent ductus arteriosus
Atrioventricular septal defect
Mitral valve prolapse
Tricuspid regurgitation

Answer 16

Turner’s syndrome - most common cardiac defect is bicuspid aortic valve (more common than coarctation of the aorta)

Turner syndrome (45 XO) is associated with:
Bicuspid aortic valve
Aortic root dilatation
Coarctation of the aorta

Question 17

summarise

Answer 17

Turner’s syndrome

Turner’s syndrome is a chromosomal disorder affecting around 1 in 2,500 females. It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner’s syndrome is denoted as 45,XO or 45,X.

Features
short stature
shield chest, widely spaced nipples
webbed neck
bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
an increased risk of aortic dilatation and dissection are the most serious long-term health problems for women with Turner’s syndrome
regular monitoring in adult life for these complications is an important component of care
primary amenorrhoea
cystic hygroma (often diagnosed prenatally)
high-arched palate
short fourth metacarpal
multiple pigmented naevi
lymphoedema in neonates (especially feet)
gonadotrophin levels will be elevated
hypothyroidism is much more common in Turner’s
horseshoe kidney: the most common renal abnormality in Turner’s syndrome

There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn’s disease

Question 18

A 14-year-old girl attends the GP concerned that she has yet to start getting periods like the rest of her peers.

On examination, she is 144cm tall and has multiple melanocytic naevi on her arms, which she holds at a wide carrying angle at rest. Cardiovascular examination is normal and she has no relevant family history.

What is the most likely diagnosis?

Familial atypical multiple mole melanoma syndrome
Imperforate hymen
Noonan syndrome
Polycystic ovarian syndrome
Turner’s syndrome

Answer 18

Short stature + primary amenorrhoea ?Turner’s syndrome

Turner’s syndrome is correct. This girl has primary amenorrhoea, short stature, skeletal abnormalities and multiple melanocytic naevi, which are all signs of Turner’s syndrome. Turner’s syndrome is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Other features include a webbed neck and shield chest. People with Turner’s syndrome are also at higher risk of other abnormalities such as a bicuspid aortic valve, coarctation of the aorta and horseshoe kidney.

Familial atypical multiple mole melanoma syndrome is incorrect. This is an autosomal dominant condition, hence unlikely because in this scenario there is no family history of multiple malignant melanomas. Nor would this account for her short stature and amenorrhea.

Imperforate hymen is incorrect. This is rare, and patients with this would likely develop significant pain and bloating upon menstruation. Further, it would not account for her skeletal abnormalities and multiple melanocytic naevi.

Noonan syndrome is incorrect. This may also cause short stature and other dysmorphic features, however, it would not explain her primary amenorrhea.

Polycystic ovarian syndrome is incorrect. This could account for primary amenorrhea but would not explain the other signs such as short stature. In contrast to Turner’s syndrome, girls with PCOS would be more likely to have advanced pubertal development due to hyperandrogenism. Therefore, Turner’s syndrome is more likely in this scenario.

Question 19

A 14-year-old girl is brought to the paediatric endocrinology clinic for a routine follow-up appointment. She was diagnosed with Turner syndrome shortly after birth due to characteristic physical features and karyotype analysis showed a complete absence of one X chromosome. Her parents express concerns about her growth, overall health, and her transition to adolescence. They have read online that people with her diagnosis are more likely to develop certain severe health problems in the long term.

What issue are they referring to?

Alzheimer’s disease
Aortic dissection
Bronchiectasis
Lymphoma of small intestine
Tetralogy of Fallot

Answer 19

Aortic dissection

An increased risk of aortic dilatation and dissection are the most serious long-term health problems for women with Turner’s syndrome

The correct answer is aortic dissection. This patient’s parents are concerned about the severe long-term effects of Turner’s syndrome. These patients may present with different and multiple congenital abnormalities, but they are usually characterised by short stature, webbed neck and wide-spaced nipples. Turner’s syndrome is characterised by an increased chance of being born with a bicuspid aortic valve instead of a normal tricuspid aortic valve. This congenital heart anomaly can lead to altered blood flow patterns, turbulence, and stress on the aortic wall. Over time, these factors can contribute to aortic dilatation, and as a consequence, aortic dissection.

Alzheimer’s disease is incorrect. This is a progressive degenerative disease associated with neurocognitive decline. People who have been diagnosed with Turner’s are not at an increased risk of developing Alzheimer’s disease. This association has been noticed between people diagnosed with Down’s syndrome.

Bronchiectasis is incorrect. This is a chronic lung disease, characterised by irreversibly dilated bronchi alongside chronic bronchial inflammation and infection. People who have been diagnosed with Turner’s are not at an increased risk of developing bronchiectasis. Multiple causes have been identified for bronchiectasis such as infection and auto-immune diseases, but there is no association with genetic disorders.

Lymphoma of small intestine is incorrect. This type of lymphoma, specifically enteropathy-associated T-cell lymphoma of the small intestine has been associated with coeliac disease, and more broadly with autoimmune disease, rather than with genetic disorders such as Turner’s.

Tetralogy of Fallot is incorrect. This is a congenital heart disease characterised by a ventricular septal defect, right ventricular hypertrophy, right ventricular outflow tract obstruction, pulmonary stenosis and an overriding aorta. It has been associated with Down’s syndrome rather than Turner’s syndrome. Additionally, it is a congenital defect rather than an issue which develops during life.

Question 20

LH (follicular phase) 54 IU/L (1-12)
FSH (follicular phase) 48 IU/L (1-9)
Antimullerian hormone (AMH) 0.1 ng/mL (0.7-3.5)
17-hydroxyprogesterone 2.1 nmol/L (1.0 - 4.5)

What is the most likely diagnosis?

Congenital adrenal hyperplasia
Constitutional delay of puberty
Functional hypothalamic amenorrhoea
Premature ovarian insufficiency
Turner’s syndrome

Answer 20

Turner’s syndrome

Short stature + primary amenorrhoea ?Turner’s syndrome

Turner’s syndrome is correct. Short stature (145cm) and primary amenorrhoea (absence of menses at 15 years) are common presenting features of Turner’s syndrome. The pathology is thought to be due to ‘streak’ ovaries, resulting in a low level of circulating oestrogen. This causes negative feedback resulting in an increase in GnRH production and therefore high circulating levels of LH and FSH, as seen in this girl. The antimullerian hormone (AMH) has recently been used as a specific marker of ovarian reserve. It is produced in the granulosa cells of ovarian follicles, so the more a woman has the higher her AMH level will be. AMH (also known as anti-mullerian inhibiting factor) also plays a role in embryology, it is produced by Sertoli cells in male fetuses resulting in the regression of the Mullerian ducts, fallopian tubes and uterus. In this woman, as her AMH is low, it implies the ovaries are insufficient, typical of Turner’s syndrome.

Constitutional delay of puberty is incorrect. This is defined as the absence of menstruation with the absence of secondary sexual characteristics at the age of 13, or the absence of menstruation and normal secondary sexual characteristics at the age of 15. The girl in this scenario is 15 years old so she has primary amenorrhoea regardless of her secondary sexual characteristics. At 15 years, it should not be assumed her delayed menstruation is constitutional, even if her family history is similar’the short stature points towards Turner’s syndrome along with the blood results supporting this diagnosis. LH and FSH levels are not elevated in pre-pubertal girls.

Congenital adrenal hyperplasia is incorrect. A mild form of this disease is due to a partial deficiency of 21 hydroxylase and results in a reduction in aldosterone and cortisol. This can present with irregular or absent periods accompanied by early onset pubic hair, acne and hirsutism. A high level of 17-hydroxyprogesterone is associated with this diagnosis. In this case, it is a normal level, making this diagnosis unlikely.

Functional hypothalamic amenorrhoea is incorrect. This is usually a result of stress, eating disorder or intense exercise resulting in depression of GnRH. One could expect to see a low BMI, which causes a low level of LH and FSH to be released into the bloodstream. In this girl, a high LH and FSH are seen making this unlikely.

Premature ovarian insufficiency is incorrect. This is caused by the ovaries entering a menopausal state early, usually before a patient’s 40s. The oestrogen level decreases resulting in a high LH and FSH level. One way to differentiate between Turner’s and premature ovarian failure is height. As this girl is 145cm, she has a short stature suggesting that Turner’s syndrome is more likely. As well as this, she has not yet started her periods at all, therefore, by definition, she cannot be experiencing early-onset menopause and hence, premature ovarian failure. Genetic phenotype testing should be done to clarify the likely diagnosis.