Overview

Turner syndrome is a genetic disorder affecting female infants. It is characterized by missing one X chromosome, either completely or partially. The symptoms of Turner Syndrome vary from person to person, but common symptoms include a webbed neck, short height, low hairline, and failure to attain puberty milestones.¹

What is Turner syndrome?

Humans have 23 pairs or 46 chromosomes in each cell of our body. The 23rd pair is called sex chromosome, and it is XX for females and XY for males. In females with Turner Syndrome, one X chromosome either is completely absent or partially missing from the XX pair.

Turner syndrome is the most common sex chromosome-linked disorder affecting 1 in 2000 to 2500 live female babies. It was first described by Henri Turner in 1938.¹

Causes of Turner syndrome

Turner Syndrome occurs because of an abnormal or absent gene in the DNA of the cells. The abnormal or absent gene is the X chromosome. Depending on the X chromosome abnormality, three types of Turner Syndrome are encountered in affected females.

Monosomy X

Nearly 45% of all Turner Syndrome cases are of this type. In monosomy X, one X chromosome is completely absent. The affected female has only 45 chromosomes in her cells. It happens when either the egg or sperm of the affected female’s biological parent is at fault.²

Mosaic Turner syndrome

Here, some cells of the affected female have a pair of sex chromosomes, while some have only one copy of X. It happens because of improper cell division during early pregnancy.²

Inherited Turner syndrome

The above two types happen randomly without any probable cause. However, this type is inherited. The biological parent of the affected female had Turner Syndrome, and it was passed on to the child. This type of Turner Syndrome happens rarely.²

Symptoms of Turner syndrome

People with Turner Syndrome have normal intelligence, but they can have difficulty to learn, memorize, calculate, and pay attention.

Depending on the type of Turner Syndrome, affected females can have a wide variety of symptoms. These symptoms also vary in severity from one person to another.

These signs and symptoms can be assessed at different stages of life.

Before birth

Chromosomal abnormalities can be assessed prenatally that is before birth by detecting some reliable markers through ultrasonography between 11-13 weeks of gestation. One of such markers is the measurement of nuchal translucency (NT). NT is the normal collection of fluid in the folds of skin at the back of the fetal neck. Normal NT measures below 3.5mm. Increased value of NT (more than 3.5mm) at the NT scan is a highly predictable marker of chromosomal abnormalities, including Turner Syndrome.^1,4

Along with increased NT, fetus with Turner syndrome can have these findings on first-trimester scan:-

• Polyhydramnios
• Oligohydramnios
• Hydrops fetalis
• Cystic hygroma
• Abnormal heart
• Horseshoe shaped kidney

At birth or during infancy

Newborns with Turner Syndrome have signs like:-

• Low hairline
• Low-set ears
• Swelling of hands and feet
• Short 4th fingers and toes
• Narrow and high roof of the mouth
• Broad chest with far-spaced nipples
• Narrow and upward-turned nails of hands and feet
• Short and wide neck with extra folds (webbed neck)

In childhood, teens, and adulthood

Signs and symptoms of Turner syndrome during these stages are:-

• Delayed growth of the child
• Below average height for the given age
• Failure to attain childhood milestones at the right time
• Failure to attain physical changes (breast development, menarche) during puberty because of ovarian failure
• Infertility

Risk factors

Turner Syndrome affects females randomly. There is no attributable risk factor linked to the abnormalities in the X chromosome. Since most cases of Turner syndrome are not inherited, family history is not a risk factor that leads to alteration or loss of X chromosome. Only in rare cases the altered gene is passed from one generation to another.^3,5

How is Turner syndrome diagnosed

Before birth

1. Amniocentesis: A procedure where the amniotic fluid and uterine cells are taken during 14-20 weeks of pregnancy to test for genetic abnormalities⁶
2. Chorionic villus sampling: In this procedure, the sample is taken from the placenta to test for chromosomal abnormalities. The placenta has the same chromosomes as that of an unborn baby. This test is done between 10-13 weeks of gestation⁶
3. Ultrasound: Ultrasound scan between 11-13 weeks for detecting increased NT, cystic hygroma, fetal hydrops, cardiac defects, and renal defects

After birth

Genetic Testing: Analysis of chromosomes by taking a blood sample or buccal swab confirms the diagnosis of Turner syndrome after birth. The test can be performed in babies, childhood, or adulthood.

Turner syndrome treatment/management

Short stature

Short stature is common among affected females. However, this is not due to decreased growth hormone. Although affected females have a normal level of growth hormone, growth hormone therapy (GRT) is effective in helping them gain average adult female height.

GRT has certain side effects. Patients undergoing GRT can develop scoliosis, intracranial hypertension, and pancreatitis. Therefore, close monitoring of the patients taking GRT is necessary to manage the condition.

Ovarian failure

Affected females present with the complaint of absent menses or delayed puberty because of ovarian failure. Delayed puberty can be treated by giving estrogen replacement therapy (ERT). Nearly all patients of Turner syndrome need ERT. ERT can be followed by progesterone replacement therapy (PRT). ERT will help to grow egg follicles and develop secondary sexual characteristics, while PRT is needed to maintain cyclic bleeding.

Infertility

Most women with Turner syndrome are infertile due to ovarian follicular depletion. However, they can opt for an IVF procedure to conceive with the help of donor eggs.

Learning disabilities

Despite normal intelligence, affected females can have learning disabilities. Psychological therapy, behaviour therapy, and special education schools can aid in managing the condition.

Differential diagnosis

Turner Syndrome can often be confused with another disorder known as Noonan syndrome, a condition that has the same characteristic features as Turner Syndrome. 

Noonan syndrome presents with symptoms like short stature, webbed neck, heart, and kidney abnormalities. However, there’s no chromosomal abnormality in Noonan syndrome. Hence, it can affect both males and females, unlike Turner syndrome, which affects only females because of an abnormality in X chromosome. Genetic testing must be done to confirm the diagnosis. 

Prognosis

Females with Turner syndrome have a three times shorter life span compared to the normal females. Heart diseases and abnormalities are the major cause of short life spans. Affected females are prone to developing aortic aneurysms, stroke, type 2 diabetes, and cardiovascular diseases. Abnormalities in kidney, and liver diseases, and epilepsy are also significant causes for decreased life spans.

Complications of Turner syndrome

As discussed above, Turner syndrome can have a spectrum of disorders, and the affected females can encounter several systemic complications and comorbidities.

Common complications in females with Turner syndrome can be:-

• Impaired hearing
• Aortic dissection
• Type 2 diabetes
• Gonadoblastoma
• Vitamin D deficiency
• Abnormal liver function
• Autoimmune diseases like celiac disease, Hashimoto’s thyroiditis

Summary

Considered the most common sex chromosome-linked disorder affecting females, Turner syndrome has no cause for the alteration or loss of X chromosome of the cell DNA. And likewise, it has no cure. Although the life expectancy of Turner syndrome patients is shorter, symptomatic treatments and optimal interventions help to manage the disorder and help affected females live a better life.