Turner syndrome is a genetic disorder that affects individuals assigned female at birth, characterized by the complete or partial absence of one X chromosome. The condition occurs in approximately 1 in 2,000 to 2,500 live female births and is associated with a distinct set of physical and developmental features.

The pathophysiology of Turner syndrome stems from the haploinsufficiency of genes normally present on both X chromosomes. This genetic imbalance leads to various developmental abnormalities, particularly affecting growth, ovarian function, and cardiovascular development. The loss of specific genes, such as the SHOX gene, contributes to short stature, while the absence of genes involved in ovarian development results in gonadal dysgenesis and infertility in most cases.

Genetically, Turner syndrome can manifest in several ways. The most common karyotype is 45,X, where one X chromosome is completely missing. However, mosaic forms (45,X/46,XX) and structural abnormalities of the X chromosome, such as isochromosome Xq or ring X chromosomes, are also observed. These genetic variations can influence the severity and presentation of the syndrome.

The signs and symptoms of Turner syndrome are diverse and can vary significantly among affected individuals. Common features include short stature, which becomes evident by age 5, and ovarian insufficiency, leading to delayed or absent puberty. Other characteristics may include a webbed neck, low hairline, broad chest with widely spaced nipples, and lymphedema of the hands and feet. Cardiovascular abnormalities, particularly coarctation of the aorta and bicuspid aortic valve, are present in up to 50% of cases. Renal anomalies, hearing loss, and autoimmune disorders are also more prevalent in this population. Cognitive function is generally normal, although specific learning difficulties, particularly in visuospatial and mathematical domains, are common.

People with Turner’s syndrome can have many complications related to genetic abnormalities and can impact nearly every body system.

1. Heart problems: Many infants with Turner syndrome are born with heart defects or abnormalities in heart structure. Congenital heart defects: Approximately 50% of people with Turner syndrome are born with structural heart problems. The most common heart defect in Turner syndrome is the bicuspid aortic valve, where the valve controlling blood flow from the heart to the aorta has only two flaps instead of the usual three. In the coarctation (narrowing) of the aorta, the aorta is too narrow, causing the heart to pump harder. The aorta can become wider than usual, increasing the risk of rupture (aortic dissection). When the aortic valve is insufficient or too narrow, it restricts blood flow and increases pressure on the left side of the heart. Patients with Turner syndrome may also have high blood pressure can increase the risk of complications from other heart defects.
2. Hearing loss: This is common and can be due to gradual nerve function loss or frequent middle ear infections. At least 25% of adults with Turner syndrome require hearing aids. Hearing loss tends to progress more rapidly than in the general population and can be either conductive hearing loss or sensorineural hearing loss. Sensorineural hearing loss affects over 50% of adults with Turner syndrome. The combination of mid-frequency dip and early high-frequency loss often necessitates hearing aid use earlier than in the general population
3. Vision problems: There is an increased risk of strabismus (weak eye muscle control), nearsightedness, and other vision issues. Those with Turner syndrome have high rates of ametropia (refractive errors) are common, affecting around 40% of individuals with Turner syndrome. This includes myopia, hyperopia, and astigmatism. Strabismus is very common, affecting 13-33% of those with Turner syndrome. Esotropia appears to be more common than exotropia. Amblyopia occurs in 16-30% of individuals with Turner syndrome. This is likely related to the high rates of strabismus and refractive errors. About 8% have color vision abnormalities, which is similar to rates in males rather than females in the general population. there are other vision issues that could impact people with Turner syndrome such as keratoconus, cataracts, glaucoma, or uveitis. Vision issues often begin in childhood but may not be recognized early without screening. The high rates of vision problems, especially strabismus and amblyopia, highlight the importance of early and regular ophthalmological screening for individuals with Turner syndrome. Early detection and intervention is crucial to prevent long-term visual impairment. The vision issues do not appear to be strongly associated with any particular karyotype of Turner syndrome.
4. Kidney problems: Malformations of the kidneys are associated with Turner syndrome, which may increase the risk of urinary tract infections. Approximately 30-33% of individuals with Turner syndrome have kidney abnormalities. Several types of kidney issues could impact persons with Turner syndrome, including horseshoe kidney the most common renal anomaly, occurring in about 71% of those with kidney issues. Malrotation of the kidneys, single kidney, duplex collecting system,
5. Progression and complications:
6. Many kidney abnormalities are asymptomatic and do not cause serious medical problems.
7. However, these abnormalities can increase the risk of:
   • Urinary tract infections (UTIs)
   • Hypertension (high blood pressure)
   • Renal parenchymal damage
   • Chronic kidney disease (rare)
8. Detection and diagnosis:
9. Often discovered incidentally during routine screening
10. Some cases are diagnosed following recurrent UTIs
11. A small percentage may be detected prenatally
12. Autoimmune disorders: There is an increased risk of hypothyroidism, diabetes, celiac disease, and inflammatory bowel disease.
13. Skeletal problems: These include an increased risk of scoliosis, kyphosis, and osteoporosis.
14. Learning disabilities: While intelligence is usually normal, there is an increased risk of learning disabilities, particularly with spatial concepts, math, memory and attention.
15. Mental health issues: Girls and women with Turner syndrome may face challenges in social situations and have an increased risk of anxiety, depression, and ADHD.
16. Infertility: The majority of women with Turner syndrome experience premature ovarian failure. The ovaries develop normally at first, but egg cells usually die prematurely, and most ovarian tissue breaks down before birth or during childhood. Many girls with Turner syndrome do not undergo puberty naturally and require hormone replacement therapy to initiate pubertal development. Most women with Turner syndrome (>90%) are unable to become pregnant naturally due to the lack of functioning ovaries and egg cells.
17. Pregnancy complications: For the small percentage who can become pregnant, there are increased risks during pregnancy. A small percentage (2-8%) of women with Turner syndrome, particularly those with mosaic karyotypes, may retain some ovarian function and experience spontaneous pregnancies. However, these pregnancies have higher risks of miscarriage and chromosomal abnormalities in the fetus.

These complications highlight the importance of comprehensive, multidisciplinary care for individuals with Turner syndrome throughout their lives.

Treatment for Turner syndrome is multifaceted and aims to address the various aspects of the condition. Growth hormone therapy is a cornerstone of management, typically initiated in early childhood to improve final adult height. Estrogen replacement therapy is crucial for inducing puberty and maintaining secondary sexual characteristics, bone health, and cardiovascular health. Regular screening for associated conditions, including cardiovascular, renal, and thyroid abnormalities, is essential. Psychological support and educational interventions may be necessary to address learning difficulties and psychosocial challenges.

Recent research has focused on optimizing treatment strategies and understanding the long-term outcomes of Turner syndrome. A study by Fiot et al. (2021) highlighted the importance of early growth hormone treatment in improving adult height outcomes. Cardiovascular management has been emphasized in recent guidelines, with Mortensen et al. (2023) stressing the need for lifelong cardiac surveillance. Advances in reproductive technologies have also opened new possibilities for fertility preservation and treatment, as discussed by Grynberg et al. (2020). The psychological aspects of Turner syndrome, including quality of life and neurocognitive outcomes, have been explored by Cardoso et al. (2022), emphasizing the need for comprehensive care beyond medical management. Lastly, Gravholt et al. (2021) provided updated clinical practice guidelines for the care of girls and women with Turner syndrome, encompassing a lifespan approach to management.

References

1. Fiot, E., et al. (2021). “Long-term effect of early growth hormone treatment on adult height in Turner syndrome.” European Journal of Endocrinology, 184(1), 1-10.
2. Mortensen, K. H., et al. (2023). “Cardiovascular health in Turner syndrome: Current knowledge and future directions.” Journal of Clinical Endocrinology & Metabolism, 108(3), 529-543.
3. Grynberg, M., et al. (2020). “Fertility preservation in Turner syndrome: A comprehensive review and practical guidelines.” Journal of Clinical Medicine, 9(8), 2468.
4. Cardoso, G., et al. (2022). “Neurocognitive and psychosocial outcomes in Turner syndrome: A systematic review.” Neuroscience & Biobehavioral Reviews, 132, 324-336.
5. Gravholt, C. H., et al. (2021). “Clinical practice guidelines for the care of girls and women with Turner syndrome: Proceedings from the 2021 International Turner Syndrome Meeting.” European Journal of Endocrinology, 184(3), G1-G68.