Turner Syndrome.. What is it?
Turner syndrome is a rare and random genetic disease afflicting only females. Turner syndrome affects multiple organs. There are 23 pairs of chromosomes (=46 chromosomes; 45, XX, or XY) within each cell of the body. In Turner syndrome, one chromosome in the form of a sex chromosome called the X chromosome is either missing completely (45, XO) or partially with loss of certain functions. Mosaicism is another event that leads to Turner syndrome. The prevalence of Turner syndrome is observed is approximately ranging from 1 birth in 2000 - 2500 live female births. Unfortunately, due to delayed diagnosis of the Turner syndrome, there has been an adverse impact on females as the age progresses. The patients show impaired sexual function, and almost half of the patients show sexual inactivity. In adolescent females, the disease often manifests with delayed puberty, secondary to premature ovarian failure. The typical feature is “Streak gonads”, which is a form of absence of cells in the tissue.
Manifestations of Turner syndrome
Turner syndrome was first defined and described by Oklahoma physician Henri Turner in 1938. The symptoms vary as the age progresses. Typically, in the female newborn, Turner syndrome can manifest with congenital lymphedema of the extremities of the body such as hands and feet, dysplasia of nail or presence of abnormalities within nail tissue, webbed neck, broad chest with widely spaced nipples, narrow and high-arched palate (a narrow, tall roof of the mouth or the hard palate), and short fourth metacarpals or metatarsals, hearing loss, kidney dysfunction, and eye or vision-related abnormalities are common associative manifestations of Turner syndrome. The prenatal diagnosis relies heavily on the sampling of chorionic-villus or amniocentesis. A karyotype analysis should be done with peripheral blood mononuclear cells first. Even if the initial karyotype testing does not indicate Turner syndrome, a second karyotype should be performed utilizing a different tissue such as skin, bladder epithelial cells, or buccal mucosa cells. Fluorescence in situ hybridization (FISH) study is an option in addition to the karyotype, which can detect abnormality in part of the DNA sequence or chromosomes regarding missing chromosomal matter. MRI, ultrasonography, and cardiovascular evaluation along with marker tests of AMH and TSH levels should be employed for confirmation of the disease.
Turner syndrome complications and management
Turner syndrome is usually not inheritable but is a random event during reproduction. During the formation of reproductive cells in a parent, a random event leads to improper segregation of the sex chromosome X in dividing cells to form gametes. Turner syndrome patients have an increased risk of complications and comorbidities such as cardiovascular malformations, diabetes, pulmonary or lung-related venous abnormalities, and coronary artery diseases. Patients with Turner syndrome also show an increase in death rate due to pneumonia, epilepsy, liver disease, as well as kidney disease.
The management of Turner syndrome is symptomatic. Management comprises age-appropriate treatment of the symptoms, complicacies, and comorbidities of Turner syndrome, to improve the quality of life of the patients. Growth hormone therapy is the most promising therapy along with estrogen therapy in Turner syndrome.
Patients' quality of life
To maximize fertility preservation, all Turner syndrome women should be evaluated in childhood. Preservation is needed early in life as the majority of women will have their ovarian reserve exhausted before adulthood due to the disease. Growth hormone therapy can occasionally expose underlying scoliosis (a condition defining a one-sided curvature of the spine frequently diagnosed in adolescents). Hence, the patients should be monitored closely every six months, regarding the position of their spines during the treatment and if needed, they should consult an orthopedic surgeon for possible corrective surgery. Some other quality of life issues with patients taking necessary growth hormone therapy are adverse effects of intracranial hypertension, pancreatitis (inflammation of the pancreas), and slipped capital femoral epiphyses (a condition defining rearrangement of bones on hip joints during teens and pre-teens years of growth). If the patient needs further assistance for growth even after administration of growth hormone, oxandrolone may be administered, or pubertal induction can be presented.
Support groups recommend the use of Turner syndrome-specific transition tool kits such as the one improved by the Endocrine Society, Hormone Health Network, and Turner Syndrome Society of the US, specifically the American College of Physicians Pediatric to Adult Care Transitions toolkit. For best care, it is recommended that a dual-energy X-ray absorptiometry or DXA scans at least in 5 years along with continued estrogen supplementation until ordinary menopausal age should be done; it can also manage bone health in women with Turner syndrome. Adequate counseling in adult Turner syndrome clinics should be performed for psychosocial issues, career options and sustenance, sexual function, contraception, fertility options as well as interpersonal relationships.
Multidimensional treatment and early diagnosis are needed to control the morbidities and further mortalities. The research needs to emphasize developing targeted therapeutics to help manage the disease in the future.
Written by: Souvik Datta, Ph.D., Manasa Tata, M.D.S., & Lawrence D. Jones, Ph.D.