Overview

Definition:
-Turner syndrome (TS) is a chromosomal disorder in females caused by a partial or complete absence of the X chromosome
-It is characterized by a variety of physical abnormalities, intellectual disability, and failure of gonadal development.
Epidemiology:
-TS affects approximately 1 in 2,500 live female births worldwide
-The incidence is consistent across different ethnic groups.
Clinical Significance: TS is crucial for pediatricians to recognize due to its multisystemic manifestations, including significant cardiovascular risks (like coarctation of the aorta), endocrine deficiencies, and skeletal anomalies, all impacting long-term health and quality of life.

Clinical Presentation

Symptoms:
-Short stature
-Webbed neck
-Low posterior hairline
-Broad chest with widely spaced nipples
-Swollen hands and feet at birth
-Learning disabilities, particularly in nonverbal skills
-Infertility
-Delayed puberty
-Amenorrhea.
Signs:
-Phenotypic features such as short stature, webbed neck (pterygium colli), low-set ears, and broad Q-angle
-Cardiovascular examination may reveal murmurs suggestive of valvular heart disease or aortic abnormalities.
Diagnostic Criteria:
-Diagnosis is confirmed by karyotype analysis revealing an abnormal X chromosome complement (e.g., 45,X or mosaicism)
-Clinical features are supportive but not diagnostic on their own.

Diagnostic Approach

History Taking:
-Detailed family history for chromosomal abnormalities
-Perinatal history including birth weight and any noted anomalies
-Developmental milestones
-Pubertal progression
-History of recurrent infections
-Absence of secondary sexual characteristics.
Physical Examination:
-Comprehensive physical examination focusing on anthropometric measurements (height, weight, head circumference), characteristic facial features, neck examination (webbing), chest examination (nipple spacing), abdominal examination, and cardiovascular assessment for murmurs or pulses
-Examination of extremities for edema or skeletal anomalies.
Investigations:
-Karyotype analysis is essential for definitive diagnosis
-Echocardiography is mandatory to screen for congenital heart defects, particularly coarctation of the aorta and bicuspid aortic valve
-Renal ultrasound to assess for structural abnormalities
-Endocrine evaluation including FSH, LH, estradiol, thyroid function tests (TSH, free T4), and growth hormone levels
-Bone age assessment.
Differential Diagnosis: Noonan syndrome (shares some features but is autosomal dominant and has different genetic basis), other genetic syndromes causing short stature, primary ovarian insufficiency, constitutional delay of growth and puberty.

Management

Initial Management:
-Early diagnosis and genetic counseling
-Referral to pediatric endocrinology and cardiology
-Initiation of screening investigations.
Medical Management:
-Growth hormone therapy for short stature
-Estrogen replacement therapy (ERT) is crucial for pubertal development and secondary sexual characteristics, typically initiated between ages 12-13 if spontaneous puberty does not occur
-Estrogen is usually given orally or transdermally, often combined with a progestin to mimic the menstrual cycle
-Doses are gradually increased
-ERT also helps in bone mineralization and cardiovascular health.
Surgical Management:
-Surgical intervention for severe congenital heart defects identified during screening, such as repair of coarctation of the aorta or valvular procedures
-Laparoscopic or open surgical repair of coarctation depends on the severity and location of the stenosis.
Supportive Care:
-Psychosocial support for the patient and family
-Educational support for learning disabilities
-Regular monitoring of cardiovascular status, thyroid function, bone density, and glucose metabolism
-Fertility counseling is important for older adolescents.

Complications

Early Complications:
-Congenital heart defects (coarctation of aorta, bicuspid aortic valve are most common)
-Renal anomalies
-Lymphedema in infancy.
Late Complications: Hypertension (often related to coarctation), cardiovascular disease, type 2 diabetes mellitus, osteoporosis, autoimmune diseases (e.g., thyroiditis, IBD), gonadal dysgenesis leading to infertility, hearing loss, neurocognitive deficits.
Prevention Strategies:
-Aggressive screening for cardiovascular and renal anomalies
-Early initiation of hormone replacement therapy to promote bone and reproductive health
-Lifestyle modifications to reduce risk of metabolic syndrome and hypertension
-Regular monitoring for autoimmune conditions.

Key Points

Exam Focus:
-Karyotype 45,X is pathognomonic
-Coarctation of aorta and bicuspid aortic valve are common cardiac defects requiring echocardiographic screening
-Estrogen therapy is essential for pubertal development and bone health, typically starting at 12-13 years
-Growth hormone is used for short stature.
Clinical Pearls:
-Always screen for coarctation of the aorta in any patient with Turner syndrome, even in the absence of murmur
-Estrogen replacement therapy should be individualized based on pubertal progression and patient response
-Early intervention with ERT can mitigate long-term skeletal and cardiovascular risks.
Common Mistakes:
-Underestimating the prevalence and severity of cardiovascular complications
-Delaying initiation of estrogen replacement therapy
-Inadequate screening for renal anomalies
-Not considering Turner syndrome in girls with unexplained short stature or pubertal delay.