Turner Syndrome: Diagnosis- Development and Management

Turner Syndrome


Turner syndrome is defined as the loss or partial loss of an X chromosome (XO) in a female. Signs and symptoms typically include short stature, gonadal dysgenesis and various somatic abnormalities. Approximately 99% of conceptions with Turner syndrome miscarry, while the remaining frequency of livebirths is 1 in 1,500 to 1 in 2,500. Turner syndrome may be suspected prenatally (in approximately two-thirds of affected fetuses) through ultrasound. Common findings include nuchal cystic hygroma, increased nuchal translucency, nonimmune hydrops, and cardiac and/or renal abnormalities. A low or elevated maternal serum α-fetoprotein may be noticed in fetuses with Turner syndrome. However, many fetuses have normal sonographic features and are detected inadvertently through karyotyping as a routine part of CVS or amniocentesis, most commonly performed for advanced maternal age.

Different sex chromosome complements have been associated with Turner syndrome. The Turner phenotype is thought to be due to the presence of one active copy of a “Turner gene” or “Turner genes” on the X chromosome. It is more than likely that these genes normally escape X inactivation and have functional Y chromosome homologs. Ernest B. Hook and Dorothy Warburton, famous geneticists, have proposed that all viable 45, X cases are cryptic mosaics with a rescue cell line (possibly in the placenta) and result from mitotic loss. Below is the karyotype of an individual with Turner syndrome.

Background and Significance

Born in 1892 in Harrisburg, Illinois, Henry Hubert Turner is noted for discovering Turner syndrome in 1938. He graduated from medical school at the University of Louisville School of Medicine in 1921 and practiced as an endocrinologist. Turner recognized common signs and symptoms such as a webbed neck, short stature, lack of secondary sex characteristics and fertility complications.  In June 1938, Dr. Turner read before the annual meeting of the Association for the Study of Internal Secretions in San Francisco his paper entitled “A Syndrome of Infantilism, Congenital Webbed Neck, and Cubitus Valgus.” He described 7 patients-6 adolescents and 1 adult. The following is an excerpt from Turner during the meeting in an interview, “I had seen a few young girls who had not matured, and they were short in stature and they had short necks with a low hair line and increased carrying angle at the elbow. And I became intrigued with them and I was wondering what in the world could do this to them. And finally, I had seen patients who on x-raying neck they did not show any absence of the cervical vertebra or any fusion of it like you find in Klippel-Feil Syndrome. They all followed a definite pattern. They were all, as I say, short in stature and had no breast development and no internal organs that we could find except perhaps with an endoscope. We could see a little nipple that might have been a cervix less than one cm. in size, and…” The classification of these symptoms led to the discovery of Turner syndrome.

Diagnosis and Management

Diagnosis and management of Turner syndrome requires an initial comprehensive and detailed evaluation followed by annual evaluations for life. Recent advances in science and technology have significantly improved the prognosis and quality of life for individuals with Turner syndrome. The diagnosis of Turner syndrome is made through chromosome analysis. Single nucleotide polymorphism (SNP) microarray genotyping has shown to be effective in the diagnosis of Turner syndrome but will not detect balanced X-autosome translocations. For any individual with 45, X cell line plus a marker or fragment, molecular SRY (sex-determining region Y) and TSPY (testes-specific protein Y-encoded) probe analysis should also be performed to rule out the presence of Y chromosomal material. A common association or hallmark of Turner syndrome is short stature. Normally, there is mild intrauterine growth restriction (IUGR), decreased growth rate in childhood, and no adolescent growth spurt. Final adult height averages about 56 inches. Growth-hormone therapy is commonly offered for this condition, usually started between 2 and 5 years of age if height is below the 5


percentile on standard curves. The injections continued until appropriate bone age or satisfactory height has been reached, which is typically around mid-adolescence.

Gonadal dysgenesis is usually present at birth. The ovaries appear normal during the first 12 weeks of gestation. This is followed by a decline in the number of follicles with very few, if any, remaining at birth. The ovaries that are present do not produce estrogen and most females will require hormone replacement therapy. Supplemental estrogen is usually started around 14-15 years of age and is coordinated to minimize compromising growth while corresponding puberty with that of peers. Estrogen supplementation promotes the development of secondary sex characteristics and combined with progesterone, establishes and maintains menses throughout adulthood. Pregnancy is possible for adult women with Turner syndrome using donor eggs, and their pregnancy rate is equal to that of women with other causes of premature ovarian failure. A complete cardiac evaluation with imaging before pregnancy in women with Turner syndrome is recommended due to the increased risk of aortic aneurysm. Fertility among women with the 45, X karyotype and without recognized mosaicism is not common. There is a high risk of miscarriage and an increased likelihood of chromosomal errors and anatomic defects in the offspring of fertile 45, X women, making a prenatal diagnosis highly recommended. Autoimmune diseases are more common in individuals with Turner syndrome. These include gastrointestinal disorders such as ulcerative colitis, Crohn disease, and celiac disease. Glucose intolerance with insulin resistance is common and there is an elevated risk of diabetes.

Cognitive/Psychologic Development

The intellectual and psychosocial characteristics of Turner syndrome can vary greatly, however, patterns of development and adaptation have been noted. The early childhood of some 45, X females may have delays in walking and other motor skills. This decreased coordination can occur into childhood and may interfere with success in sports and athletics. Most females with Turner syndrome do not exhibit signs of language impairment and early language development is often unaffected.

Early research associated individuals with Turner syndrome to have intellectual disability however, this is no longer accurate. A vast review of studies of IQ in females with Turner syndrome indicated that the mean verbal IQ was not significantly different from females who do not have Turner syndrome. The impairment of perceptual and spatial thinking has been associated with several related cognitive impairments, such as difficulty mentally rotating geometric shapes, orienting to left-right directions, drawing human figures, and solving arithmetic problems. Brain MRI studies have shown decreases in parietal gray and occipital white matter in Turner syndrome. Neuropsychologic profiles have acknowledged strengths in verbal processing. Approximately 50 percent of girls diagnosed with Turner syndrome need some type of special education during the school years. Specifically, mathematics and penmanship are areas in which the affected struggle with. However, learning difficulties are not limited to any single academic area. When any learning difficulties are identified, early and intensive intervention is highly recommended. It is found that these cognitive deficits have lasted until adulthood in women with Turner syndrome, with or without estrogen replacement therapy.

Behavioral characteristics of Turner syndrome appear to vary with the developmental level. Preadolescent girls have been shown to have increased incidence if ADHD and difficulty concentrating. Adolescents have been observed to be more anxious, depressed, and socially withdrawn and to have fewer friends. Girls with Turner syndrome will develop a stronger sense of self-esteem if they experience success and are encouraged to develop their own special abilities. Turner syndrome support groups can help counter the sense of isolation sometimes experienced by those individuals affected and their families. Sharing experiences and information often provide great benefits and resources.

Karyotype variations

Half of all individuals with Turner syndrome have a 45, X karyotype. Many chromosomal variants can also produce a Turner syndrome phenotype. The three most common forms are 45,X,  46,X,i(Xq),  and 45,X/46,XY, with an incidence rate of 50%, 17% and 4%, respectively. The chart titled Figure 1 lists the karyotype and incidence percentage various females with Turner syndrome. It is estimated that less than 1% of individuals with 45, X survive to birth with this karyotype of Turner syndrome. Monosomy X accounts for approximately 15% of all spontaneous miscarriages. The mechanism of chromosome loss is probably mitotic in origin. The parental origin of the missing X seems to influence Turner syndrome stigmata, including those related to the kidney, eye, body weight and lipid profile. Advanced maternal age is not associated with an increased incidence of Turner syndrome. The 45, X karyotype is normally noted in individuals with Turner syndrome who are the most severely affected, but the clinical features can vary greatly. Intellectual disability is not typically associated with the 45, X karyotype.

In the 46,X,i(Xq) karyotype, the isochromosome Xq is the most common structural rearrangement of the X chromosome and is present in approximately 15-20 percent of individuals with Turner syndrome. The isochromosome usually consists of two q arms joined at the centromere, with no short arm present. In all cases, females have a Turner phenotype with short stature, but their remaining somatic features may be less pronounced. Many individuals with 46,X,i(Xq) will have ovarian dysgenesis and some may be fertile. These individuals are also more likely to have a higher incidence of autoimmune disorders, including Hashimoto thyroiditis, inflammatory bowel disease and diabetes mellitus. Isochromosome Xq is rarely found in spontaneous abortions, or miscarriages, but is frequent in postnatal diagnoses of Turner syndrome.

The 45,X/46,XY karyotype can produce phenotypes from females with Turner syndrome with or without intellectual disability, to males with ambiguous genitalia and/or gonadal dysgenesis, to almost normal males. Prenatal counseling should be offered to discuss gonadal surveillance.

Figure 1


Incidence (%)

45, X


46, X,i(Xq)


45, X/46, XX


45, X/46, X,r(X)


46, XXq2,  46, XXp2,  46, X,i(Xp)


45, X/46, XY


Prenatal counseling

Genetic counseling of parents with an intrauterine diagnosis of Turner syndrome normally includes discussion of short stature, which will involve the use of human growth therapy. Gonadal dysgenesis in the fetus resulting in infertility will be likely and hormonal therapy can enable females to experience normal pubertal development and pregnancy via egg donation may be an option. The parents should also expect other physical abnormalities such as cardiac malformations, webbed neck and renal anomalies may be present. High-resolution ultrasounds approximately 20 weeks gestation can help differentiate fetuses who are seriously affected and those that have mild manifestations. The ultrasound can also visualize the genitals to identify any discrepancies between karyotype and phenotype. The genetic counselor should express that intellectual disability is not a characteristic of Turner syndrome, but may be noticed with individuals who express the karyotype 45,X/46,XY. There is a risk of difficulty in motor or learning skills. Early intervention is extremely beneficial, and management is no different from children with normal chromosomes and similar developmental problems. Variability among girls with Turner syndrome is substantial and prediction about any child’s prognosis is not possible.

Overall Prognosis

Individuals affected with Turner syndrome typically can expect to live a relatively normal life. Although life expectancy is slightly shorter than individuals who are unaffected, life expectancy can be improved by managing symptoms such as obesity, diabetes mellitus and hypertension. Medications and other therapies and can also help females experience puberty and menarche along with their peers. Women who choose to have children can do so via a donor egg and can have a normal pregnancy. Major technologies have greatly increased life expectancy and will increase in the years to come with new medications and scientific breakthroughs.


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    , vol. 14, no. 4, Aug. 2004, pp. 179–184.
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