What Is Turner Syndrome

It is a genetic condition affecting babies assigned females at birth (AFAB) and is characterised by the loss or partial loss of the second X chromosome. It occurs in about 1 in 2500 live AFAB births worldwide.¹ The signs and symptoms are quite variable, non-specific and can differ between individuals. The symptoms can also develop slowly over time and be subtle. This condition, however, is often associated with short stature and a failure to reach puberty. 

Overview

Turner Syndrome is one of the most  common genetic conditions but only affects AFAB babies . It is named after Henry Turner, 1938, who was the first doctor to report on the condition in medical literature. 

Causes of Turner Syndrome

Genetic information is the genetic code carried from one generation to the next.  In humans, it is coded on 23 pairs of chromosomes. There are 22 pairs of chromosome called autosomes and the 23 pairs are called sex-chromosomes. Among these pairs, one is received from the mother and one from the father. The mother always passes on an X chromosome while  the father can pass on an X or a Y chromosome. A baby AFAB normally has 2 X chromosomes (XX) and a baby assigned males at birth (AMAB) usually has one X and one Y chromosome (XY). As a result of receiving the Y chromosome, the foetus develops male characteristics. 

In Turner syndrome, the baby only receives one complete sex-chromosome, an X chromosome, whereas the other X chromosome is missing, partially missing or altered. This chromosome change is random and not attributed to the parents' age or other condition. 

The genetic changes of Turner Syndrome can be down to four different causes.²

• Monosomy - The absence of an X chromosome in every cell in the body. This would be due to an error in the mother's egg or the father’s sperm
• Mosaicism - An error in cell division in the early stages of the foetus development which results in some cells having two X chromosomes and some having one
• X chromosome changes -A  cells have one complete and one altered X chromosome. This can occur in the egg or sperm so that all cells have one complete and one altered copy or it can occur in the early stages of foetal development so that some cells have two complete X chromosomes and some have one complete and one altered chromosome
• Y Chromosome material - In rare cases of Turner Syndrome, some cells have one X chromosome and some cells have one X chromosome but with some Y chromosome material. These babies are AFAB but can have an increased risk of cancer called gonadoblastoma

Despite the above, Turner Syndrome is often more simply classified into two types, 

• Classic Turner Syndrome(non-mosaic) - Where all cells lack one X chromosome.
• Mosaic Turner Syndrome - Cells vary in chromosomal content, with some having both X chromosomes and others having an incomplete amount of X chromosomes.  This type includes Mosaicism, X chromosome change and Y chromosome material points raised above.

Signs and symptoms of Turner Syndrome

The signs and symptoms of Turner Syndrome are variable from individual to individual, non-specific, can develop slowly over time and can be subtle.  Turner Syndrome is diagnosed and managed by a specialist doctor who manages each case individually. 

However, there are some features that are common in Turner Syndrome cases. The most common is short stature. The child may initially display normal growth, especially up to the age of three. However, this will slow as the child will not display the normal pubertal growth spurt. It is sometimes this absent pubertal growth spurt is the reason to present to medical teams for diagnosis. If untreated, most children with Turner Syndrome will be below normal average height.

In addition, Turner Syndrome children will have a failure of the ovaries to develop. This may fail to show sexual development associated with puberty, which occurs between the ages of 8 and 14.

. Again, this is a common reason for people to present to medical teams for diagnosis in this age group. Children will require hormone therapy to achieve breast development, menstruation, normal body contours and bone development.³ It is important to note that although they have underdeveloped ovaries, their vagina and uterus (womb) develop normally, so that after treatment with female hormones, they can have a normal sex life, should they wish to. 

Intelligence is usually normal in Turner Syndrome but some can develop learning difficulties,especially in visuospatial awareness. Some Turner Syndrome patients can also have difficulties in some social situations.

Other features include - 

• Short neck with a webbed appearance
• Low hairline at the back of the head
• Low-set ears and hearing loss that sets in earlier than normal age-related hearing changes
• Narrow fingernails and toenails that turn upwards
• A broad chest with widely set nipples
• Swollen hands and feet, especially at birth caused by a buildup of excess fluid
• Teeth problems
• Cardiac defects
• Receding or small lower jaw
• Short fingers and toes
• High,narrow roof of the mouth (palate)
• Arms that turn outwards at the elbows
• Eye conditions such as droopy eyelids, squint, lazy eye, cataracts, short sight and eyes that slant downwards

In addition, there are other medical conditions that Turner Syndrome can make you more likely to develop and these include

• Cardiovascular Problems - About half of Turner Syndrome patients can have heart and blood vessel problems and these include, high blood pressure and abnormalities of the heart valves and a narrowing of the aorta (main blood vessel leaving the heart)⁴
• Bone Problems - Osteoporosis is an issue if the patient hasn’t received hormone replacement treatment and even when hormone replacement is given there is a debate as to how effective it is in preventing osteoporosis.⁵ It is also important to screen for scoliosis (curvature of the spine) as this has a higher frequency in Turner Syndrome than the general population
• Autoimmune Disorders - the risk of autoimmune disorders is twice as high in Turner Syndrome than in the general population.⁶ This includes Hashimoto’s thyroiditis, coeliac disease, type 1 diabetes, alopecia areata, inflammatory bowel disease, juvenile rheumatoid arthritis and some skin disorders

Management and treatment for Turner Syndrome

If a doctor suspects Turner Syndrome, the patient should be referred for specialist diagnosis. This is done by analysing the chromosomes in a blood sample.

If the obstetrician sees any possible signs in a baby antenatally, they can test the chromosomes using amniotic fluid in a procedure called amniocentesis.⁷ The signs include diffuse oedema (swelling of the body issues with fluid), cystic hygroma (cysts seen in the baby’s head and neck), certain kidney/heart/neck/cranial abnormalities or retarded growth. If the test is performed pre-birth, the parents must receive detailed genetic counselling prior to the test. 

Turner Syndrome needs management throughout their whole life, initially by a paediatric endocrinologist and then by an adult endocrinologist. 

Key areas to manage:

• Short Stature - This can be improved by treatment with a growth hormone. This is thought to be able to increase height by between 5 to 8 cm although actual height achieved depends on mid-parental height, age at initiation of therapy, duration of therapy and dose⁸
• Failure to enter puberty - Although f Turner Syndrome children enter puberty spontaneously, most do not. Most, therefore, require puberty induction with hormone therapy (oestrogen/progesterone) to achieve breast formation, womb maturation and normal bone mass density. The normal method is hormone patches, starting at age 11 to 12 years old⁹
• Developmental Issues - Most Turner Syndrome children have normal development. A small number can have some challenges with memory, processing speed and task handling. In addition, challenges with mathematics, reading comprehension, facial expression recognition and motor coordination are noted, as well as autism spectrum disorders and ADHD (attention deficit hyperactivity disorder) disorders. ¹⁰ This would be treated in a similar way as those with this condition without Turner Syndrome, although the medicines may not be as effective
• Cardiovascular disorders - These are reasonably common and contribute to 50% of those Turner Syndrome patients that die before normal life expectancy.¹⁰ Regular cardiac and high blood pressure monitoring is recommended
• Ear Conditions - Regular monitoring in the ear clinic for middle ear infections and early onset hearing loss is recommended¹¹
• Other Conditions - As mentioned earlier, Turner Syndrome means the patient is at increased risk from autoimmune conditions such as Coeliac disease and awareness of this link is important in long term patient management. 

FAQs

How is Turner Syndrome diagnosed

Turner Syndrome is diagnosed via a specialist hospital team led by a paediatric endocrinologist and later an adult endocrinologist. The condition can be suggested due to certain physical features but a diagnosis is made only after analysis of the patient’s chromosomes. This can be done using a blood sample or via amniocentesis if the diagnosis is suggested before birth. 

How can I prevent Turner Syndrome

Turner Syndrome is not linked to any activity or to maternal or paternal age. Therefore it is not possible to prevent Turner Syndrome. However, it is reported that 99% of foetuses with Turner Syndrome sadly abort spontaneously. It is thought that 10% of all first-trimester miscarriages are due to Turner Syndrome.¹⁰

What are the types of Turner Syndrome

It is often divided into two types - ‘Classic Turner Syndrome’, where all cells lack one X chromosome and ‘Mosaic Turner Syndrome’, where cells vary in chromosomal content, with some having both X chromosomes and others having an incomplete amount of X chromosomes.

Who are at risk of Turner syndrome

There are no known environmental risks of Turner Syndrome and it affects all regions and races in the world equally.¹²

How common is Turner Syndrome

It affects about one in every 2500 AFAB babies worldwide.¹

When should I see a doctor

If you have any concerns about your general health or your child’s health then you should see a doctor as soon as possible. In relation to Turner Syndrome, if you have any concerns regarding any of the symptoms or signs mentioned above, then please see your doctor, especially with regard to growth, puberty or fertility.

Summary

Turner Syndrome is a genetic condition that affects about one in 2500 AFAB babies born worldwide. It is not possible to prevent and has no risk factors in relation to the mother, father or antenatal health. It is caused by the loss or partial loss of the second X sex chromosome. Although some features may be seen antenatally and at birth, in most affected children, many of the signs and symptoms are subtle and develop over time. The most common are short stature and failure to enter normal pubertal development. The condition requires lifelong monitoring by a paediatric and adult endocrinologist.