Turner Syndrome

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Turner syndrome

The identification of Turner syndrome

Turner syndrome (also referred to as gonadal dysgenesis) is a rare genetic disorder that only affects females. Approximately one in 2,000-5,000 females in the general population are affected with Turner syndrome. This is a large percentage considering that about 99% of pregnancies with fetuses affected with Turner syndrome spontaneously abort, usually during the first trimester of pregnancy. It is also estimated that 10% of all spontaneously aborted fetuses result from Turner syndrome.

Genetic defects

First described by Dr. Henry Turner in 1938, Turner syndrome was later found to be due to a loss of genetic material in one of the two X-chromosomes. There are several ways in which Turner syndrome arises. Females have two X-chromosomes, while males have an X-chromosome and a Y-chromosome. While a Y-chromosome contains genes required for development of testicles in males, both X-chromosomes are required for normal ovarian development in females. The majority of Turner syndrome cases are caused by a sporadic event during a specific stage of cellular division, where an X-chromosome is lost. Normally, when sex cells divide, an equal amount of genetic material is divided into each cell . During fertilization of the egg, if the sex cell void of the X-chromosome is fertilized by a sex cell that is missing the other X-chromosome, the result is only one sex chromosome . If the fetus survives, the baby will be born with Turner syndrome. A fertilized egg with only one Y-chromosome is incompatible with life.

Turner syndrome can also result from the loss of a single X-chromosome after fertilization, sometime during embryonic development. This particular condition is referred to as mosaicism, with clinical manifestations being proportional to the percentage of cells missing the X-chromosome. Finally, Turner syndrome can result due to a defective X-chromosome such as large deletion. The clinical consequences vary depending on the nature of the structural abnormality of the X-chromosome. In the case X-chromosome deletions, where affected individuals are fertile, there is potential for a recurrence risk in pregnancies from an affected female. Otherwise, there is typically little recurrence risk (if any) in subsequent pregnancies or in individuals with Turner syndrome since the majority of these individuals are infertile.

Clinical manifestations of Turner syndrome

There are a broad spectrum of clinical manifestations associated with Turner syndrome that can involve anything from major heart defects to minor defects in tissue development. Some affected individuals only manifest a few clinical features, while others have many abnormalities consistent with the disorder. The majority of individuals with Turner syndrome have short stature and loss of ovarian function. Other disorders include learning difficulties, skeletal abnormalities (e.g., webbed neck, low posterior hair line), lymphedema (swelling of a part of the body due to an obstruction or deficiency of the lymphatic drainage system), heart and kidney abnormalities, infertility , obesity , formation of keloids (thick scars), and thyroid gland dysfunction (hypothyroidism).

Loss of gene function and developmental consequences

Short stature is usually present in females with Turner syndrome. This is partially due to a loss of the SHOX gene , which encodes a protein important for long bone growth. The height in adults with Turner syndrome ranges from 143-145 cm (approximately 4 ft 8 in). Treatment using growth hormones during early childhood development can increase growth by a few inches in some cases. The loss of the X-chromosome genes may also be related to the intrauterine growth retardation, a gradual decline in growth rate during childhood, and the absence of a pubertal growth spurt. Females with Turner syndrome have abnormal body proportions characterized by markedly shortened lower extremities.

Lost X-chromosome genes that are involved in the regulation of ovarian development and function results in a failure of individuals with Turner syndrome to enter into puberty at a normal age. Although 10% of females with Turner syndrome will go through puberty spontaneously, most will require hormone therapy for development of secondary sexual characteristics and menstruation. Without hormonal intervention, most teenagers that undergo partial breast development and menstruate spontaneously will eventually cease further development and menstruation. A few pregnancies have been reported and most likely occur prior to ovarian failure. The time of initiation of therapy varies with each female but usually begins no later than 15 years of age. Various estrogenic and progestational agents and schedules have been used as hormone therapy to maintain their secondary sexual development and prevent osteoporosis (bone degradation) later in life. Although most women with Turner syndrome do not have functional ovaries, pregnancy may be possible through in vitro fertilization (assisted reproductive technology).

Renal abnormalities occur in 1/3 to 1/4 of females with Turner syndrome. The most common abnormality is a horseshoe kidney. Cardiac abnormalities are also common, with the coarctation of the aorta being the most common defect. This is a condition that results from a severe constriction a major blood vessel in the heart, can be treated with surgery , and occurs in 5-10% of affected children. Turner syndrome females generally have normal intelligence, however, most may exhibit learning disabilities, especially with regard to spatial perception , visual-motor coordination, and mathematics . As a result, the nonverbal IQ in Turner syndrome tends to be lower, with a relatively normal verbal IQ. Females with Turner syndrome may also be socially immature for their age and may need support in developing independence and social relationships.