Turner Syndrome:
Karyotype: The classic karyotype is 45,X (monosomy X).
Aetiology: Typically caused by paternal meiotic non-disjunction, though maternal non-disjunction can also occur. The loss of the entire X chromosome is the most common cause.
Mosaicism: A significant proportion of individuals have mosaicism, with common patterns being 45,X/46,XX or other structural anomalies of the X chromosome (e.g., isochromosome Xq, ring chromosome X). The presence of a 45,X cell line is a defining characteristic. A key recent development is the recognition that the clinical phenotype is highly variable and depends on the specific karyotype and degree of mosaicism. Individuals with 45,X/46,XY mosaicism require specific monitoring for signs of virilisation and a significant risk of gonadoblastoma.
Pregnancy Outcomes
Fetal Loss: While up to 99% of 45,X conceptuses are miscarried, this is a complex figure. The syndrome is the only monosomic condition compatible with life, which is a key point to retain.
Pre-natal diagnosis: Increasingly, diagnosis is made antenatally via non-invasive prenatal testing (NIPT) or invasive methods like chorionic villus sampling (CVS) or amniocentesis. This allows for early counselling and planning of care.
Antenatal & Neonatal Features
Antenatal Scan: Fetal ultrasound may show hydrops fetalis, cystic hygroma (a form of severe nuchal thickening), and congenital heart or renal abnormalities. These findings should prompt a referral for invasive diagnostic testing.
Newborn: Classic features include oedema of the hands and feet (due to lymphatic dysplasia), a webbed neck, and a low posterior hairline. Other signs may include a broad chest with widely spaced nipples.
Features in Childhood
Growth: Short stature is a universal finding. Growth failure becomes evident from 3-5 years of age with a significant height deficit compared to the general population.
Endocrine: Ovarian dysgenesis is nearly universal, leading to primary ovarian insufficiency (gonadal failure). This results in a lack of pubertal onset and infertility. Spontaneous puberty and even menses can occur in some mosaic individuals (up to one-third of 45,X/46,XX mosaics) but a significant proportion will still require hormone replacement therapy (HRT).
Other Systems: Persistent lymphoedema may resolve in early childhood. Hearing issues, particularly sensorineural hearing loss, are common and can progress. Eye problems such as ptosis and strabismus are also noted.
Neurocognition: Cognition is typically normal. However, specific learning difficulties, particularly with visuospatial and non-verbal skills, are common and can impact social and academic function. Behavioural issues like impulsivity and poor attention may also be present.
Clinical Monitoring & Recent Developments
The 2024 International Clinical Practice Guidelines have significantly updated surveillance recommendations. The key is a multidisciplinary, lifespan approach.
Growth & Puberty:
Height & Weight: Continue monitoring. Growth hormone (GH) therapy is a cornerstone of management and is recommended to be initiated as early as 2-4 years of age if growth failure is evident. This can significantly improve final adult height.
Pubertal Development: The most recent guidelines recommend inducing puberty with incremental, low-dose transdermal oestrogen patches starting at an age that is in line with peers (11-12 years). Oral oestrogens are a less preferred option due to first-pass liver effects. Progesterone is added later to protect the uterus.
Cardiovascular:
Blood Pressure: Check annually from diagnosis. Promptly treat hypertension as it is a significant risk factor for aortic dissection.
Imaging: Echocardiogram (ECHO) and cardiac MRI (CMR) are now the standard of care. Initial imaging should occur at diagnosis. Surveillance should be repeated every 5 years in the absence of significant findings, or more frequently if risk factors like aortic dilation or bicuspid aortic valve (BAV) are present. All individuals with Turner Syndrome should have cardiac imaging before any planned pregnancy.
Renal:
USS: A renal tract ultrasound scan at diagnosis remains standard to identify anomalies such as horseshoe kidney.
Endocrine & Metabolic:
TSH: Check annually due to a high risk of autoimmune hypothyroidism (Hashimoto’s thyroiditis).
Glucose & Lipids: Fasting glucose, HbA1c, and lipid profile should be checked annually from adolescence, or earlier if there is obesity or a family history of diabetes. There is an increased risk of type 2 diabetes and metabolic syndrome.
Coeliac Disease: Screening for coeliac disease is now recommended due to increased prevalence, with checks at 2-3 years of age and then every two years.
Other Surveillance:
Ophthalmology: A specialist ophthalmology assessment is needed for ptosis and strabismus.
Hearing: Formal audiometry testing is recommended at diagnosis and then regularly throughout life.
Fertility: Counselling on fertility preservation options, such as oocyte cryopreservation, is a crucial part of care for adolescents, particularly those with mosaicism, as spontaneous conception is possible but rare.