Turner syndrome

Introduction

Turner syndrome is a chromosomal disorder affecting females, characterized by partial or complete loss of one X chromosome. It occurs in approximately 1 in 2,500 live female births and is associated with distinctive physical features, growth deficits, and gonadal dysfunction. Early recognition and multidisciplinary management are critical for improving outcomes.

Genetics and Pathophysiology

Chromosomal Abnormalities

Turner syndrome arises from anomalies of the X chromosome, leading to a range of genetic and phenotypic manifestations.

• Monosomy X (45,X): Complete absence of one X chromosome, the most common karyotype in Turner syndrome.
• Mosaicism: Presence of two or more different cell lines, such as 45,X/46,XX, which can result in variable clinical features.
• Structural abnormalities of the X chromosome: Includes deletions, ring X chromosomes, and isochromosomes that disrupt normal gene function.

Pathophysiological Mechanisms

The clinical features of Turner syndrome result from reduced dosage of X-linked genes and subsequent developmental effects.

• Effect on growth: Haploinsufficiency of the SHOX gene contributes to short stature and skeletal abnormalities.
• Impact on ovarian development: Ovarian dysgenesis leads to primary amenorrhea and infertility.
• Cardiovascular effects: Abnormal vascular development can result in bicuspid aortic valve, coarctation of the aorta, and increased risk of hypertension.

Clinical Features

Physical Characteristics

Turner syndrome presents with a recognizable set of physical features that may be apparent at birth or develop during childhood.

• Short stature, often evident by age 5
• Webbed neck with low hairline
• Low-set ears and epicanthal folds
• Broad chest with widely spaced nipples
• Lymphedema of hands and feet in infancy

Gonadal and Reproductive Features

Ovarian dysfunction is a hallmark of Turner syndrome, affecting pubertal development and fertility.

• Ovarian dysgenesis leading to streak ovaries
• Primary amenorrhea due to absent or delayed puberty
• Infertility in most affected individuals

Cardiovascular Features

Cardiovascular anomalies are common and can have long-term health implications.

• Bicuspid aortic valve
• Coarctation of the aorta
• Hypertension

Other Associated Features

Additional organ systems may be affected, contributing to comorbidities.

• Renal anomalies such as horseshoe kidney
• Hearing loss, often sensorineural
• Endocrine issues including hypothyroidism
• Neurocognitive profile characterized by normal intelligence with specific learning difficulties, especially in mathematics and spatial tasks

Diagnosis

Clinical Diagnosis

Diagnosis is initially suspected based on characteristic physical features and growth patterns.

• Recognition of short stature, webbed neck, and lymphedema
• Assessment of delayed or absent puberty

Laboratory and Genetic Testing

Definitive diagnosis requires cytogenetic analysis to confirm chromosomal abnormalities.

• Karyotype analysis to identify monosomy X or mosaicism
• Fluorescence in situ hybridization (FISH) and molecular tests to detect structural abnormalities or low-level mosaicism

Imaging Studies

Imaging is used to evaluate associated structural anomalies, particularly of the heart and kidneys.

• Echocardiography to assess for bicuspid aortic valve and aortic coarctation
• Renal ultrasound to detect structural anomalies such as horseshoe kidney

Management

Growth and Hormonal Therapy

Management of Turner syndrome focuses on addressing growth deficits, inducing puberty, and supporting reproductive health.

• Growth hormone therapy: Administered in childhood to improve final adult height.
• Estrogen replacement: Initiated in adolescence to induce secondary sexual characteristics and promote bone health.
• Fertility preservation: Options include cryopreservation of oocytes or use of donor eggs for assisted reproduction.

Cardiovascular Management

Early detection and monitoring of cardiovascular anomalies are essential to prevent complications.

• Regular echocardiography to monitor aortic dimensions and valve function
• Management of hypertension with lifestyle modification and medications
• Surgical correction for severe structural defects such as coarctation of the aorta

Other Supportive Care

Comprehensive care involves monitoring and treating associated medical conditions.

• Management of hypothyroidism and other endocrine disorders
• Hearing and vision assessments with corrective interventions as needed
• Psychosocial support, educational interventions, and counseling to address learning difficulties and emotional well-being

Complications and Prognosis

Turner syndrome is associated with several long-term complications that require ongoing monitoring and intervention.

• Increased risk of cardiovascular disease, including aortic dilation and dissection
• Osteoporosis and increased fracture risk due to estrogen deficiency
• Infertility in the majority of affected individuals
• Overall life expectancy is slightly reduced, often related to cardiovascular complications, but quality of life can be improved with appropriate multidisciplinary care

Genetic Counseling and Prenatal Diagnosis

Genetic counseling is essential for families affected by Turner syndrome to understand inheritance, recurrence risk, and reproductive options.

• Inheritance patterns: Turner syndrome is typically sporadic, with a low recurrence risk in subsequent pregnancies.
• Prenatal testing: Options include chorionic villus sampling, amniocentesis, and non-invasive prenatal testing to detect X chromosome anomalies.
• Family counseling: Provides information on medical management, potential complications, and psychosocial support for affected individuals and their families.

References

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