Turner Syndrome: Definition and Clinical Features
Turner syndrome is defined as the complete or partial absence of one X chromosome in a phenotypic female, most commonly presenting as 45,X karyotype, which leads to increased cardiovascular mortality from both structural and ischemic heart disease, particularly aortic dissection. 1
Genetic Basis
- Turner syndrome affects approximately 1 in 2,500 liveborn girls and results from complete or partial loss of the second X chromosome, often in mosaic karyotypes 1, 2
- The most frequent karyotype is monosomy of X chromosome (45,X) found in about 63.3% of cases, followed by isochromosome of Xq (46,XisoXq) in 16.7%, and other variants including mosaicism 3
- While parental age does not affect the complete loss of one X chromosome, the paternal X chromosome is absent in approximately three-quarters of patients with Turner syndrome 4
Clinical Manifestations
Primary Features
- Short stature and ovarian failure are the most prevalent findings 1
- Delayed puberty, hypergonadotropic hypogonadism, and infertility are common 2, 4
- Approximately 99% of Turner syndrome conceptions result in pregnancy loss; prenatal ultrasound may show cystic hygroma and hydrops 4
Cardiovascular Abnormalities
- Women with Turner syndrome have an increased cardiovascular mortality rate from both structural and ischemic heart disease, especially aortic dissection 1
- Between 10% and 25% of patients have a bicuspid aortic valve 1
- Aortic coarctation is present in approximately 8% of patients 1
- Approximately 50% of patients have cardiovascular defects including BAV (15%-30%), aortic coarctation (7%-18%), and ascending aortic dilation (33%) 1
- The risk of aortic dissection is significantly higher than in the general population, with a population-based incidence of 36:100,000 Turner syndrome years (1.4%) compared with 6:100,000 in the general Danish population 1
- The average age of aortic dissection is 31 years, with less than half of patients surviving the event 1
Other Associated Conditions
- Endocrine disorders including type 1 and type 2 diabetes mellitus 2
- Osteoporosis and autoimmune disorders 2, 5
- Neurocognitive deficits 5
- Hypothyroidism and deafness 6
Cardiovascular Risk Assessment and Management
Diagnostic Imaging
- All women with Turner syndrome should undergo baseline cardiovascular imaging to evaluate for bicuspid aortic valve, coarctation of the aorta, and enlargement of the ascending aorta 7
- Cardiac MRI is recommended at diagnosis to evaluate for associated congenital cardiovascular abnormalities and to measure aortic diameters 1
- For patients with Turner syndrome who are ≥15 years old, indexing of aortic diameter to body size by calculating the aortic size index (ASI) is recommended 1
Surveillance Recommendations
- For patients with Turner syndrome and no additional risk factors for aortic dissection:
- For patients with Turner syndrome and an ASI >2.3 cm/m², surveillance imaging at least annually 1
- For patients with risk factors for aortic dissection (BAV, coarctation, hypertension, dilated aorta), more frequent imaging is recommended based on aortic diameter, ASI, and growth rate 1, 7
Surgical Intervention
- In patients ≥15 years old with an ASI of ≥2.5 cm/m² plus risk factors for aortic dissection, surgical intervention to replace the aortic root, ascending aorta, or both is reasonable 1
- Prophylactic replacement of the aortic root or ascending aorta should be considered when the ASI >23 mm/m² or the aortic height index (AHI) >23 mm/m 7
Special Considerations
Pregnancy
- Pregnancy is associated with a higher risk of aortic dissection, especially with pre-existing cardiovascular abnormalities 7
- A thorough cardiovascular evaluation is mandatory before attempting pregnancy 7
- Pregnancy in Turner syndrome carries substantial risks and requires extensive pre-conception counseling and monitoring 7
Physical Activity
- Physical activity should be encouraged but modified based on cardiovascular status and aortic dimensions 7
Management Approach
- A multidisciplinary approach to focused adult care is needed due to multiple potential comorbidities 6
- Hypertension should be treated aggressively according to general guidelines 7
- Beta-blockers and/or ARBs may be considered to inhibit aortic growth, similar to management in Marfan syndrome 7
- Growth hormone therapy and estrogen replacement therapy are important components of management 3
Turner syndrome requires lifelong monitoring due to the increased risk of cardiovascular complications and other associated conditions. Early diagnosis and appropriate management can significantly improve quality of life and reduce mortality in affected individuals.