Sharon H. Travers, M.D.
Assistant Professor of Pediatrics
University of Colorado Health Sciences Center
What is Turner Syndrome?
Turner syndrome is a genetic disorder that occurs exclusively in girls and results
from an abnormality of a chromosome. Chromosomes are material in the cells of the
body which contain genes that determine each person's characteristics.
Everyone has 22 pairs of chromosomes in addition to a pair of sex chromosomes, called
X and Y. A female has two X chromosomes (referred to as a XX karyotype), and a male
has one X and one Y chromosome (XY karyotype).
In Turner syndrome, one of the X chromosomes is missing (XO karyotype) or is structurally
abnormal (XX(abnormal)). This results in a variety of physical manifestations (findings)
with the most common being short stature.
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What causes Turner Syndrome?
There is no known cause of why this chromosomal abnormality occurs. Neither parent
is responsible for this happening nor can they prevent it.
It is not associated with parental age or environmental factors such as maternal
drug abuse, alcohol consumption, medication, cigarette smoking, etc. Parents who
have one daughter with Turner syndrome do not have an increased risk of having additional
daughters with this syndrome.
The incidence of Turner syndrome is approximately 1:2000 live female births. However,
the chromosomal abnormality is actually more common than this as 99% of XO fetuses
do not survive beyond 28 weeks gestation, and the XO karyotype occurs in 1 out of
15 miscarriages.
Girls with Turner syndrome may have some normal cells in their body (46,XX) with
other cells showing the abnormal karyotype 45, XO or 46, XX(abnormal). These girls
are described as Turner mosaics and generally have less manifestations of the syndrome.
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How does it cause disease?
The X chromosome contains important genes for traits like stature and ovarian function.
Consequently, by having a missing or abnormal X chromosome, girls with Turner syndrome
will have findings that relate to what those genes code (for example, short stature
and ovarian dysfunction).
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Clinical Findings in Turner Syndrome?
There are multiple findings in girls with Turner syndrome and they occur with varying
frequencies. Consequently, not all features will necessarily be present in each
affected girl. In fact, short stature in many girls may be the only manifestation.
A list of the common findings are presented in the Table and discussed in the following
sections.
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Clinical Findings in Turner Syndrome and Their Incidence
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Finding
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Approximate Incidence(%)
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Short stature
|
100
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Short neck
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40
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|
Scoliosis
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35
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|
Characteristic facial features
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35
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|
Webbed neck
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25
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|
Low posterior hairline
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42
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Edema of hands/feet
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22
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Ovarian failure
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95
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Infertility
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99
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|
Moles
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25
|
|
Heart abnormalities
|
55
|
|
Kidney abnormalities
|
39
|
|
Thyroid disease
|
35
|
|
|
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Skeletal Growth Disturbances?
The most common physical abnormality in girls with Turner syndrome is short stature.
This is thought to be primarily a result of an abnormality of the growth response
of the skeleton. Affected girls usually show an early decline in their growth within
the first few months of life followed by a normal or near normal growth velocity
until between 3 and 5 years of age. After 3 to 5 years, growth becomes increasingly
abnormal (see Figure) so that the height of a Turner girl falls further and further
below the normal curve. The average Turner adult height reached is 4 feet 8 inches,
compared to an average adult female height of 5 feet 41/2 inches. There are genetic
influences so that Turner girls who have tall parents typically will be taller than
the average Turner height and likewise girls with short parents will be shorter.
Figure. Growth curve for girls with Turner Syndrome. (Provided as a service of Genentech,
Inc. � Genentech, Inc., 1987. All rights reserved.)
Some girls with Turner syndrome have a distinctive facial appearance, and this is
due in part to abnormal development of the bones in the face. Characteristic features
include a small chin, downward droop of the outer corners of the eyes, and an abnormally
arched palate (roof of mouth)
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Lymphatic Development
Many girls with Turner syndrome have maldevelopment of their lymphatic system. The
lymphatic system is a collection of vessels that bring fluid from body tissues back
to the heart. As a result of lymphatic obstruction, there is extra fluid in a Turner
fetus referred to as lymphedema. There is often a large collection of fluid in the
neck, and when this fluid eventually decompresses, the skin remains stretched and
can appear "webbed". The stretching of the neck skin also results in a low posterior
hair line, low-set and rotated ears, and extended growth of the eyebrows. Lymphedema
of the hands and feet in a Turner fetus may cause abnormal development of fingernails
and toenails. If this edema is present in a newborn, there is the appearance of
"puffy" hands and feet. This typically resolves within the first few weeks/months
after birth.
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Ovarian Failure?
The ovaries in girls with Turner syndrome initially develop normally in the fetus.
However, if there are not two normal X chromosomes in the ovarian cells, there is
early egg loss and scarring of the ovaries. This process can occur entirely prenatally
or within the first few months or years of life. The ovaries also produce the hormone
estrogen which is responsible for sexual development in girls. Consequently, the
majority of girls with Turner syndrome do not show spontaneous puberty such as breast
development and menstrual periods. Most girls are also infertile.
In approximately 10 to 20% of Turner girls, there will be some ovarian function
at puberty that allows for a little bit of breast development. A small percent of
this group will also have normal periods, and an even smaller percent (less than
1% of all girls with Turner syndrome) will actually be fertile. Pregnancy has been
reported in a small number of girls with Turner syndrome; however, there is an increased
risk of chromosomal abnormalities in the children of these women. Girls who are
Turner mosaic have a greater chance of retaining some or all of their ovarian function.
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Heart Abnormalties?
There is an increased risk of heart abnormalities in Turner girls. Coarctation of
the aorta is a condition where there is a narrowing of the aorta (the main blood
vessel coming from the heart). This occurs in 15 to 20% of Turner girls and is more
common in girls with a webbed neck. If found, this abnormality requires surgical
treatment. A more common abnormality that occurs in up to 30% of girls is a bicuspid
aortic valve. The normal valve of the aorta has three leaflets whereas a bicuspid
valve only has two. Girls with bicuspid valves need cardiology follow-up but do
not require surgical repair. High blood pressure may also occur in Turner girls
but is not typically evident until adulthood. There is also a risk of dilation of
the aorta that if not diagnosed and treated can rupture and cause significant morbidity
and/or mortality. It is not clear whether girls who have normal hearts are at risk
for dilation of the aorta or if it only occurs in those with abnormal hearts (i.e.,
coarctation or bicuspid valve). Because of this uncertainty, it is the opinion of
this author that girls with normal hearts have a cardiology evaluation every 4-5
years.
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Kidney Abnormalties?
Kidney abnormalities occur in 30-40% of girls with Turner syndrome. These abnormalities
typically involve the structure, position, or blood vessels of the kidneys. Usually
there are no health consequences of these abnormalities. Rarely patients require
surgery or have any kidney impairment.
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Otitis Media (middle ear infections) and hearing loss?
One of the most common medical problems in girls with Turner syndrome is recurrent
ear infections. Abnormal development of the bones of the face leads to an abnormal
relationship between the middle ear and eustation tube, which creates a predisposition
to fluid collection in the middle ear and infection. Hearing loss may be a consequence
of recurrent ear infections and fluid in the middle ear. This is referred to as
conductive hearing loss.
Hearing loss that is not associated with ear infections (referred to as sensorineural
hearing loss) also occurs in a high percentage (about 64%) of Turner girls. This
hearing loss can become worse with age; consequently, girls with Turner syndrome
should have regular assessments of their hearing.
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Other Medical Conditions?
Other disorders that are seen with increased frequency in girls with Turner syndrome
include hypothyroidism and gastrointestinal disorders. Diabetes mellitus may also
occur but generally not until adolescence or adulthood.
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Neuro-psychological Findings
The intelligence of girls with Turner syndrome is normal; however, there is often
impairment in motor skills, visual-motor coordinating, and visualizing objects in
relation to each other. This type of impairment is termed nonverbal learning disability
(NVLD), often manifested by a discrepancy between verbal and performance IQ scores
with verbal scores being higher.
Girls with Turner syndrome and NVLD have difficulty with mathematics, tasks requiring
manual dexterity, and poor directional sense (i.e., difficulty with left and right).
These girls may also show social immaturity as they have difficulty understanding
social and nonverbal cues.
These neuro-psychological findings are seen in a high percentage of, but not all
Turner girls. Consequently, it may be beneficial for girls to have neuro-psychological
testing early on so parents and teachers can help girls compensate for this problem.
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How Do You Diagnose Turner Syndrome
A girl who has the clinical findings suggestive of Turner syndrome should have a
chromosomal analysis done by a simple blood draw. The blood is sent to a laboratory
where specialists separate the chromosomes in the white blood cells and count and
examine them carefully.
Since poor growth may be the only finding in many girls with Turner syndrome, this
test should be strongly considered in any girl who has unexplained short stature.
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Follow-up Studies
Once the diagnosis of Turner syndrome has been established by chromosome analysis,
additional studies and tests are indicated. Because of the risk of hypothyroidism,
thyroid tests should be done on a yearly basis.
In girls who are older than 10 years, blood studies can also be done to assess for
ovarian function. An ultrasound of the kidney allows for detection of any abnormality.
If this study is normal, it does not need to be repeated.
A cardiology consultation should be obtained in all girls, and part of this evaluation
generally includes an echocardiogram (ultrasound of the heart). Girls with Turner
syndrome should also be referred to a pediatric endocrinologist as soon as the diagnosis
is made.
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Treatments
Growth hormone therapy has been shown in several studies to increase final height
in girls with Turner syndrome by up to 3-4 inches. Turner syndrome is one of the
three FDA approved indications for growth hormone treatment in children.
At this time, growth hormone therapy should be considered as soon as a Turner girl
has dropped below the fifth percentile of the normal female growth curve.
Growth hormone is safe and has only a few rare adverse side effects. A pediatric
endocrinologist monitors girls on growth hormone therapy every 3-4 months for response
and possible side effects. Currently, patients receive growth hormone as a daily
subcutaneous injection (just under the skin).
In girls who have ovarian failure, estrogen is started sometime between ages 12
and 14 years to allow for pubertal development. Progesterone (another important
hormone that the ovary makes) is typically added 1 to 2 years after estrogen is
started. Both of these hormones can be taken orally as tablets; estrogen is also
available as a patch preparation.
Although the majority of Turner girls are infertile, they can be the recipient of
an embryo (donated egg which is fertilized in vitro) and can carry a pregnancy successfully
to term.
Other treatments are indicated according to the clinical findings, i.e., hypothyroidism,
heart abnormalities, etc.
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Research
There is currently a national multi-center study giving growth hormone to toddler
girls (ages 9 months to 4 years) to see if it can prevent the early fall off in
growth that girls with Turner's syndrome have. Frequency of ear infections, and
hearing and development assessments are also monitored in this study. The
Turner's Syndrome Society web site has information on this study and others.
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Links
http://www.turner-syndrome-us.org
http://members.tripod.com/tsmagicmom/index.html
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References
Lippe BM: Turner Syndrome. In Sperling MA (ed): Pediatric Endocrinology. Philadelphia,
WB Saunders, 1996, pp. 387-421.
Rosenfeld RG, Attie KM, Frane J, et al: Growth hormone therapy of Turner's syndrome:
Beneficial effect on adult height. J Pediatr 132:319, 1998.
Rosenfeld RG, Tesch LG, Rodriguez-Rigau LJ, et al: Recommendations for diagnosis,
treatment, and management of individuals with Turner syndrome. The Endocrinologist
4:351. 1994.
About the Author
Dr. Travers is an Assistant Professor of Pediatrics at the University of Colorado
Health Sciences Center. She is board certified in both Pediatrics and Pediatric
Endocrinology.
She is a clinician at The Children's Hospital of Denver and sees children with a
variety of endocrine disorders. Her clinical and research interests include Turner
Syndrome and obesity in childhood.
Copyright 2012 Sharon H. Travers, M.D., All Rights Reserved
