Course:MEDG550/Student Activities/Turner's Syndrome

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Turner's Syndrome, also referred to as Monosomy X, refers to a genetic condition involving the sex chromosomes. Females with Turner's Syndrome have a missing or structurally different X chromosome. This results in a variety of symptoms that look different from person to person. These symptoms may include short stature, heart problems, infertility, high blood pressure, middle ear infection, and facial differences.

Genetics

Genetic Cause

Human genetic information is packaged into structures called chromosomes. These chromosomes exist in pairs. One pair, called the sex chromosomes, determines whether an individual is male or female. In females these are two X chromosomes, and in males, one X and one Y chromosome. Individuals with Turner’s Syndrome are females with only one X chromosome (referred to as 45X females). The second X chromosome may be missing in all cells of the body or only in some cells. In some cases, they may have a second X chromosome that is structurally altered.

Typical humans have 46 chromosomes (23 pairs). As shown in this panel, an individual with Turner’s Syndrome usually has only one X chromosome.

In about half of Turner’s Syndrome cases, the second X chromosome is missing in all cells of the body. In 5-10% of cases, there is a second X chromosome that is structurally altered in all cells of the body. In the remainder of the cases, only some cells of the body have a missing/altered X chromosome, and the remainder have the typical two X chromosomes. [1]

Inheritance

While Turner's Syndrome is a genetic disorder, it is not thought to run in families. It is possible that a mother who has one child affected with Turner's Syndrome is at a higher risk to have another pregnancy with Turner's Syndrome, but this is not currently thought to be the case[2].

Family Planning

Women with Turner's Syndrome are usually infertile due to insufficient or absent ovarian function. Some women choose the option of utilizing in vitro fertilization with egg donors. Pregnancy rates from this procedure are in the range of 50-60%. Women with Turner's Syndrome who become pregnant should be closely monitored during the pregnancy[3].

In very rare cases, women with Turner's Syndrome who are menstruating have been reported to become pregnant. In these situations, there is a risk of congenital anomalies in the fetus of about 30%[3].

Prevalence

Turner's Syndrome occurs in 1 in 2500 to 1 in 3000 live births[1]. It is estimated that 3% of all females conceived have this condition, and only about 1 in 100 pregnancies with Turner's Syndrome survive to term. It is estimated that up to 15% of spontaneous pregnancy losses are a result of Turner's Syndrome[4].

Diagnosis and Supporting Findings

Karyotyping

In individuals or fetuses suspected of Turner’s Syndrome, a karyotype is performed to assess the number and structure of the chromosomes, through which a diagnosis is made[5]. The absence of a second X chromosome or the presence of a second sex chromosome that is characteristically structurally different is diagnostic of Turner’s Syndrome [1]. Prenatally, this test requires amniocentesis (sampling of the amniotic fluid surrounding the fetus) or chorionic villus sampling (sampling of a part of the placenta). In some situations, a Turner's Syndrome karyotype is discovered when amniocentesis or chorionic villus sampling is done for another reason. In adults and children, it is performed on blood from a blood draw.  

Ultrasound

While ultrasound is not a diagnostic procedure, some findings from a detailed ultrasound during pregnancy are associated with an increased likelihood of Turner's Syndrome. These findings are listed below[5]:

  • Increased nuchal translucency (collection of fluid at the back of the neck)
  • Cystic hygroma (fluid filled sack in the head and neck area)
  • Coarctation of aorta (narrowing of the vessel that carries blood to the body)
  • Left-sided cardiac defects
  • Brachycephaly (flattened back of skull)
  • Kidney abnormalities
  • Polyhydramnios (excess amniotic fluid)
  • Oligohydramnios (not enough amniotic fluid)
  • Growth restriction

Maternal Serum Screening

Maternal serum screening is conducted during pregnancy as a means of detecting some fetal abnormalities. Several proteins are analyzed from maternal blood. Patterns in these proteins can be suggestive of certain conditions, but as with ultrasound, are not diagnostic. In some cases, these patterns can be misidentified for a higher risk of Down Syndrome[6].

Clinical Findings

As shown in the top panel, girls with Turner's Syndrome often have webbing of the neck. The lower panel shows the results of a surgery to remove this webbing.

If a diagnosis is not made prenatally, other clinical findings or combinations of findings can prompt a physician to initiate investigations for Turner's Syndrome through a karyotype. These findings are listed below[5]:

Newborns and Infants

  • Edema (swelling) of hands and feet
  • Webbed neck
  • Left-sided cardiac defects
  • Low hairline
  • Low set ears
  • Small jawbone

Children

  • Short stature
  • Slowing growth rate
  • Elevated levels of FSH
  • Cubitus valgus
  • Characteristic hand and nail abnormalities
  • Characteristic facies (facial expression/appearance)
  • High arched palate
  • Otis media (middle ear inflammation)

Adolescents

  • Absence of breast development by age 13
  • Arrested puberty
  • Absence of menstrual bleeding or stopped menstrual bleeding
  • Elevated FSH
  • Unexplained short stature

Other Features

Clinical Variability

Typical clinical features in girls and women with Turner's Syndrome are short stature, ovarian failure leading to infertility and preventing puberty, webbed neck, cardiac abnormalities, low tolerance for glucose, thyroid disease, and hearing loss[7]. Individuals with Turner's Syndrome vary widely in their features. Many parents notice these symptoms in the first few years of life, but some children are not diagnosed until they miss their normal pubertal growth spurt[1]. In the case where a woman has only some cells affected, symptoms may be so subtle that she may never be aware of her condition[1].

Psychosocial Concerns

While most individuals with Turner's Syndrome have normal intelligence, some (~10%) will have significant developmental delays requiring assistance into adult life[1]. Another 70% of patients have normal intelligence and a learning disability - specifically in regards to non-verbal and visuospatial learning[1]. If this is present, individuals tend to struggle with mathematics, driving, multitasking, and social functioning[1].

Socially, individuals have been reported to struggle with poor self-esteem, social isolation, immaturity, and anxiety. Some individuals find it difficult to read body language and facial expressions due to non-verbal learning disabilities. Likely because of this, individuals with Turner's Syndrome are less likely to enter into sexual relationships, and do so at an older age. Additionally, they are often employed below the level expected based on their education. Despite this, most adults report satisfaction with their lifestyle and do not feel isolated[1].

Life Expectancy

The life expectancy of an individual with Turner's Syndrome who survives the first year of life is reduced by up to 13 years[8]. The most common cause of death for adults with Turner's Syndrome is heart disease[8].

Management

Management of Turner's Syndrome depends is based on the concerns of each patient[1]. Children with Turner's Syndrome are often treated with growth hormone for their short stature, although the effectiveness of this treatment is uncertain. They undergo regular screening for heart concerns and may require surgery depending on the severity of their condition. Hormone replacement therapy is usually initiated at around the age of 14 years. Hearing aids and treatment for cataracts may also be required. Finally, some children may benefit from training in reading social cues and counselling to deal with anxiety[1].

Resources

Turner Syndrome Society of Canada: http://www.turnersyndrome.ca/

Turner Syndrome Foundation: https://turnersyndromefoundation.org/

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Sybert, Virginia P. (2004). "Turner's Syndrome". New England Journal of Medicine. 351.12: 1227–1238.
  2. Larizza, Daniela (2011). "Familial occurrence of Turner Syndrome: casual event or increased risk?". Journal of Pediatric Endocrinology and Metabolism. 24: 223–225.
  3. 3.0 3.1 Saenger, Paul (1996). "Turner's Syndrome". The New England Journal of Medicine. 335: 1749–1754.
  4. Cockwell, Annette (1991). "A cytogenetic and molecular study of a series of 45X fetuses and their parents". Journal of Medical Genetics. 28: 151–155.
  5. 5.0 5.1 5.2 Saenger, Paul (2001). "Recommendations for the Diagnosis and Management of Turner Syndrome". The Journal of Clinical Endocrinology and Metabolism. 86: 3061–3069.
  6. Saller Jr., Devereux (1992). "Multiple-marker screening in pregnancies with hydropic and nonhydropic Turner syndrome". American Journal of Obstetrics and Gynecology. 167: 1021–1024.
  7. Kesler, SR (2007). "Turner Syndrome". Child and Adolescent Psychiatric Clinics of North America. 16: 709–722.
  8. 8.0 8.1 Price, WH (1986). "Mortality ratios, life expectancy, and causes of death in patients with Turner's Syndrome". Journal of Epidemiology and Community Health. 40: 97–102.