Overview
Definition:
Turner syndrome (TS) is a genetic disorder affecting females, characterized by the absence of all or part of one X chromosome
Short stature is a hallmark feature, often appearing in early childhood and becoming pronounced over time
Growth hormone (GH) deficiency or impaired GH action contributes significantly to this short stature.
Epidemiology:
TS occurs in approximately 1 in 2,000 to 2,500 live female births worldwide
It is one of the most common sex chromosomal abnormalities in females
The majority of cases result from sporadic nondisjunction events during gametogenesis.
Clinical Significance:
Understanding and effectively managing short stature in Turner syndrome is crucial for optimizing a patient's growth trajectory, achieving adult height potential, and improving overall quality of life
Timely intervention with growth hormone therapy can significantly impact final height and psychosocial well-being.
Clinical Presentation
Symptoms:
Short stature is the most consistent feature, often noted by parents or pediatricians in early childhood
Other associated features may include delayed puberty, infertility due to ovarian dysgenesis, webbed neck, low hairline, lymphedema of hands and feet at birth, and cardiovascular or renal anomalies
Some individuals may present with learning difficulties.
Signs:
Growth parameters below the third percentile for age and sex
Typical dysmorphic features may include a broad chest with widely spaced nipples, low-set ears, small jaw (micrognathia), and cubitus valgus (increased carrying angle of the elbow)
Ovarian dysgenesis can lead to lack of secondary sexual characteristics at puberty.
Diagnostic Criteria:
Diagnosis is confirmed by karyotyping demonstrating a missing or partially missing X chromosome (e.g., 45,X
46,XX mosaicism
or structural abnormalities of the X chromosome)
Height below the third percentile in a phenotypic female with suggestive clinical features warrants karyotyping
Measurement of IGF-1 and IGFBP-3 can help assess GH secretion status.
Diagnostic Approach
History Taking:
Detailed birth history, including any signs of intrauterine growth restriction or neonatal lymphedema
Growth history, noting the age of onset of growth deceleration and parental height
History of pubertal delay or absence of menarche
Family history of short stature or chromosomal abnormalities
Assessment for associated congenital anomalies.
Physical Examination:
Careful anthropometric measurements (height, weight, head circumference) plotted on growth charts
Detailed examination for characteristic dysmorphic features of Turner syndrome: webbed neck, low posterior hairline, wide-set nipples, edema of extremities, cubitus valgus
Cardiac and renal assessments are essential.
Investigations:
Karyotyping is the gold standard for diagnosis, performed on peripheral blood leukocytes
Assessment of thyroid function (TSH, fT4), cardiac evaluation (echocardiogram, ECG), renal ultrasound, and audiometry are standard
Bone age assessment via hand-wrist X-ray can predict remaining growth potential
Baseline IGF-1 and IGFBP-3 levels are recommended to assess GH secretory capacity.
Differential Diagnosis:
Other causes of short stature in girls include familial short stature, constitutional delay of growth and puberty, growth hormone deficiency, hypothyroidism, chronic illness, malnutrition, skeletal dysplasias, and other chromosomal abnormalities
The presence of characteristic dysmorphic features and a positive karyotype strongly supports TS.
Management
Initial Management:
Confirmation of diagnosis via karyotyping
Comprehensive baseline investigations including cardiac, renal, and endocrine assessments
Initiation of growth hormone therapy if indicated for short stature.
Medical Management:
Growth hormone (GH) therapy is the mainstay for treating short stature in Turner syndrome
It is typically initiated when height falls below the third percentile or when growth velocity is significantly reduced
Common regimens involve daily subcutaneous injections of recombinant human GH (rhGH)
Dosing is usually weight-based, ranging from 0.04-0.06 mg/kg/day (approximately 0.3-0.45 IU/kg/week)
Therapy is continued until near-adult height is achieved, typically guided by growth velocity and patient/family goals
Oxandrolone, an anabolic steroid, may be considered in combination with GH in some cases, particularly in older girls, to accelerate growth and improve final height, though its use requires careful monitoring for side effects.
Hormone Replacement Therapy:
Estrogen replacement therapy is initiated around the typical age of puberty (11-13 years) to promote secondary sexual development and maintain bone health, especially in individuals with primary ovarian insufficiency
This is usually initiated with low-dose ethinyl estradiol or conjugated estrogens, gradually increased, and later combined with a progestin to induce menstrual cycles
This is distinct from GH therapy for growth.
Supportive Care:
Psychosocial support for the patient and family is vital, addressing potential concerns about growth, fertility, and body image
Regular monitoring of growth, pubertal development, and associated medical conditions
Nutritional assessment and guidance are important to ensure adequate intake for optimal growth
Education regarding fertility preservation options should be offered.
Complications
Early Complications:
While GH therapy itself has a good safety profile, potential side effects can include transient hyperglycemia, scoliosis progression (though more often associated with rapid growth), and injection site irritation
Rare complications include idiopathic intracranial hypertension.
Late Complications:
Cardiovascular abnormalities (coarctation of the aorta, bicuspid aortic valve), renal anomalies (horseshoe kidney), autoimmune disorders (thyroiditis, type 1 diabetes), hearing loss, osteoporosis, and infertility are significant long-term concerns
Poorly managed short stature can lead to psychosocial challenges and reduced quality of life.
Prevention Strategies:
Close monitoring for cardiovascular and renal abnormalities with regular imaging and screening
Early diagnosis and management of hypothyroidism and autoimmune conditions
Prompt initiation of estrogen replacement therapy to ensure pubertal development and bone health
Comprehensive endocrine and psychosocial follow-up.
Prognosis
Factors Affecting Prognosis:
The overall prognosis depends on the extent of phenotypic abnormalities, presence of associated organ system involvement, and timely, effective management
With modern GH therapy, the adult height can be significantly improved from historical averages
Early diagnosis and consistent adherence to treatment regimens are key.
Outcomes:
Growth hormone therapy can increase adult height by an average of 5-10 cm
Early initiation of GH therapy before the age of 4-5 years often leads to better outcomes
Successful puberty and appropriate hormonal replacement contribute to improved quality of life
Fertility remains a significant concern for most individuals.
Follow Up:
Lifelong follow-up is essential
This includes regular growth assessments, monitoring of pubertal development, cardiovascular and renal surveillance, thyroid function tests, audiometry, and bone mineral density assessments
Periodic psychosocial assessments are also crucial
Transition to adult care specialists should be planned.
Key Points
Exam Focus:
Karyotyping is essential for TS diagnosis
GH therapy is indicated for short stature, dosed by weight
Estrogen replacement therapy is for puberty/bone health, separate from GH
TS is associated with cardiac, renal, and autoimmune conditions.
Clinical Pearls:
Start GH therapy as early as possible for maximum height gain
Monitor growth velocity closely (aim for >7 cm/year)
Consider bone age assessment to guide treatment duration
Counsel patients and families about fertility and long-term health surveillance.
Common Mistakes:
Delaying GH therapy due to perceived cost or complexity
Confusing the indications for GH therapy (growth) versus estrogen therapy (puberty/bone health)
Inadequate screening for associated organ system abnormalities
Underestimating the psychosocial impact of short stature.