Turner Syndrome

A genetic condition affecting development in females due to missing or altered X chromosome

Table of Contents

Overview

Turner syndrome is a chromosomal condition that affects only females, occurring when one of the X chromosomes is completely or partially missing. Named after Dr. Henry Turner who first described it in 1938, this condition affects approximately 1 in 2,500 female births worldwide. The syndrome is characterized by a variety of medical and developmental features, with short stature and loss of ovarian function being the most common.

The condition results from a random error during the formation of reproductive cells and is not inherited from parents. While Turner syndrome can be diagnosed at any age, it may be detected before birth through prenatal screening, at birth due to physical features, during childhood because of growth delays, or at puberty when sexual development is absent or delayed. The severity and specific features vary widely among affected individuals, depending on the type and extent of chromosomal abnormality.

Despite the challenges associated with Turner syndrome, with appropriate medical care and support, most girls and women with this condition can lead healthy, productive lives. Early diagnosis and intervention are crucial for managing the various health issues associated with the syndrome and optimizing outcomes. Advances in hormone therapy, assisted reproductive technologies, and comprehensive care approaches have significantly improved the quality of life for individuals with Turner syndrome.

Symptoms

The signs and symptoms of Turner syndrome vary significantly among affected individuals and may be subtle or more pronounced. Features can be present at birth, develop during childhood, or become apparent at puberty.

Physical Features

At Birth and Infancy

  • Lymphedema (swelling) of hands and feet
  • Webbed neck (extra skin folds)
  • Low-set ears
  • Broad chest with widely spaced nipples
  • Low birth weight
  • Heart defects (especially coarctation of aorta)
  • Kidney abnormalities

Childhood and Adolescence

  • Short stature (most common feature)
  • Delayed puberty or absent sexual development
  • Learning difficulties, especially with math and spatial concepts
  • Social difficulties
  • Attention deficit problems
  • Frequent ear infections
  • Hearing problems

Medical Complications

Cardiovascular

  • Congenital heart defects (30-50% of cases)
  • High blood pressure
  • Aortic dilation
  • Bicuspid aortic valve

Endocrine and Metabolic

  • Hypothyroidism (thyroid problems)
  • Diabetes or glucose intolerance
  • Osteoporosis
  • Obesity tendency
  • High cholesterol

Reproductive Issues

  • Ovarian dysgenesis (underdeveloped ovaries)
  • Infertility (most cases)
  • Absent or irregular menstruation
  • Need for hormone replacement

Psychological and Emotional Symptoms

Other Features

  • Dental problems
  • Vision problems
  • Autoimmune disorders
  • Gastrointestinal issues
  • Lymphatic abnormalities

Causes

Turner syndrome is caused by the complete or partial absence of one X chromosome in some or all cells of the body. This chromosomal abnormality occurs randomly and is not inherited.

Chromosomal Variations

Classic Turner Syndrome (45,X)

  • Complete absence of one X chromosome
  • Occurs in about 50% of cases
  • Usually associated with more severe symptoms
  • All cells are affected

Mosaic Turner Syndrome

  • Some cells have two X chromosomes, others have one
  • Accounts for 15-25% of cases
  • Symptoms may be milder
  • Varies depending on proportion of affected cells

Structural Abnormalities

  • Partial deletion of X chromosome
  • Ring chromosome (ends joined together)
  • Isochromosome (duplication of one arm)
  • Various other structural changes

Mechanism of Occurrence

  • Random error during cell division - Nondisjunction
  • Lost during early development - After fertilization
  • Not inherited - Sporadic occurrence
  • Not related to parental age - Unlike some other chromosomal conditions

Genetic Factors

Important genes on the X chromosome affected:

  • SHOX gene - Responsible for height and bone development
  • Genes affecting ovarian function
  • Genes involved in cardiovascular development
  • Genes affecting lymphatic system

Why Only Females?

  • Males require Y chromosome for survival
  • 45,Y karyotype is not viable
  • Females can survive with one X due to X-inactivation
  • Some genes escape X-inactivation, causing symptoms

Risk Factors

Turner syndrome occurs randomly, and there are very few known risk factors. Most cases are not preventable or predictable.

Established Risk Factors

  • Female sex - Only affects females
  • Random occurrence - No clear environmental causes
  • Not hereditary - Parents don't pass it on

Factors That DON'T Increase Risk

  • Maternal age (unlike Down syndrome)
  • Paternal age
  • Previous pregnancies
  • Environmental exposures
  • Parental health conditions
  • Medications during pregnancy

Recurrence Risk

  • Having one child with Turner syndrome doesn't increase risk for future pregnancies
  • Risk remains the general population risk (1 in 2,500)
  • Prenatal testing available for reassurance
  • Genetic counseling recommended

Detection Risk Factors

Factors that may lead to earlier detection:

  • Abnormal prenatal ultrasound findings
  • Increased nuchal translucency
  • Cystic hygroma in fetus
  • Abnormal maternal serum screening
  • Advanced prenatal testing (amniocentesis, CVS)

Complications Risk Factors

Factors affecting severity of complications:

  • Type of chromosomal abnormality
  • Percentage of affected cells (in mosaicism)
  • Early diagnosis and treatment
  • Access to specialized care
  • Compliance with monitoring and treatment

Diagnosis

Turner syndrome can be diagnosed at different life stages using various methods. Early diagnosis allows for timely intervention and better management of associated conditions.

Prenatal Diagnosis

Screening Tests

  • Ultrasound findings
    • Increased nuchal translucency
    • Cystic hygroma
    • Heart defects
    • Kidney abnormalities
    • Growth restriction
  • Cell-free DNA testing - Non-invasive screening
  • Maternal serum screening - May show abnormalities

Diagnostic Tests

  • Amniocentesis - Chromosome analysis of amniotic fluid
  • Chorionic villus sampling (CVS) - Earlier testing option
  • Karyotype analysis - Gold standard for diagnosis

Postnatal Diagnosis

Clinical Features Prompting Testing

  • Lymphedema in newborn
  • Webbed neck
  • Heart defects
  • Short stature in childhood
  • Delayed puberty
  • Infertility workup

Diagnostic Methods

  • Karyotype analysis
    • Blood sample chromosome study
    • Can detect all forms of Turner syndrome
    • Standard 30-cell analysis
    • May need more cells for mosaicism
  • FISH (Fluorescence In Situ Hybridization)
    • Rapid detection method
    • Good for mosaicism
    • Specific X chromosome probes
  • Chromosomal microarray
    • Detects small deletions
    • More detailed analysis

Additional Testing After Diagnosis

Baseline Evaluations

  • Cardiac evaluation (echocardiogram, ECG)
  • Renal ultrasound
  • Hearing assessment
  • Thyroid function tests
  • Liver function tests
  • Glucose tolerance test
  • Bone density scan

Growth Assessment

  • Height and weight measurements
  • Growth velocity tracking
  • Bone age X-ray
  • IGF-1 levels

Differential Diagnosis

Conditions to distinguish from Turner syndrome:

  • Noonan syndrome
  • Constitutional growth delay
  • Growth hormone deficiency
  • Primary ovarian insufficiency from other causes
  • SHOX gene mutations

Treatment Options

Treatment for Turner syndrome is tailored to address specific symptoms and complications. A multidisciplinary team approach provides comprehensive care throughout life.

Growth Hormone Therapy

  • Early initiation - Usually between ages 4-6
  • Daily injections - Subcutaneous administration
  • Duration - Continue until growth plates close
  • Benefits
    • Increases final adult height by 5-8 cm
    • Improves body composition
    • May enhance bone density
  • Monitoring - Regular growth assessments and IGF-1 levels

Hormone Replacement Therapy

Estrogen Therapy

  • Initiates puberty (usually age 12-14)
  • Low-dose start with gradual increase
  • Promotes breast development
  • Improves bone health
  • Enhances overall well-being

Progesterone Addition

  • Added after 2 years of estrogen or breakthrough bleeding
  • Protects uterine lining
  • Establishes regular cycles
  • Various formulations available

Cardiac Management

  • Regular monitoring
    • Annual blood pressure checks
    • Echocardiograms every 3-5 years
    • MRI for aortic evaluation
  • Treatment of defects
    • Surgical repair when needed
    • Blood pressure management
    • Antibiotic prophylaxis if indicated

Other Medical Management

Thyroid Treatment

  • Levothyroxine for hypothyroidism
  • Annual thyroid function monitoring
  • Dose adjustments as needed

Hearing and ENT Care

  • Regular hearing tests
  • Prompt treatment of ear infections
  • Hearing aids if needed
  • ENT specialist follow-up

Bone Health

  • Calcium and vitamin D supplementation
  • Weight-bearing exercise
  • Bone density monitoring
  • Osteoporosis prevention

Fertility Options

  • Spontaneous pregnancy - Rare but possible (2-5%)
  • Egg donation - Most common option
  • Fertility preservation - Experimental in young girls
  • Adoption - Alternative family building
  • Pregnancy monitoring - High-risk management needed

Psychological Support

  • Counseling for adjustment issues
  • Support groups
  • Educational accommodations
  • Social skills training
  • Treatment for depression or anxiety
  • Family therapy

Lifestyle Management

  • Healthy diet to prevent obesity
  • Regular exercise program
  • Diabetes prevention strategies
  • Regular medical follow-up
  • Transition to adult care planning

Prevention

Turner syndrome cannot be prevented as it occurs randomly during cell division. However, early detection and management can prevent or minimize complications.

Primary Prevention

  • No known prevention methods exist
  • Not caused by parental actions or exposures
  • Cannot be prevented by lifestyle changes
  • Genetic counseling for family planning

Secondary Prevention (Early Detection)

  • Prenatal screening and diagnosis
  • Newborn evaluation for suspicious features
  • Growth monitoring in childhood
  • Evaluation of delayed puberty
  • Fertility workup when appropriate

Preventing Complications

Cardiovascular

  • Regular cardiac monitoring
  • Blood pressure control
  • Healthy lifestyle habits
  • Avoid smoking
  • Maintain healthy weight

Metabolic

  • Diabetes screening
  • Weight management
  • Regular exercise
  • Healthy diet
  • Thyroid monitoring

Bone Health

  • Adequate calcium and vitamin D
  • Weight-bearing exercise
  • Hormone replacement therapy
  • Avoid smoking and excess alcohol
  • Fall prevention strategies

Optimizing Outcomes

  • Early diagnosis and intervention
  • Regular multidisciplinary care
  • Adherence to treatment plans
  • Psychological support
  • Educational accommodations
  • Transition planning to adult care

When to See a Doctor

Early diagnosis and regular monitoring are crucial for optimal management of Turner syndrome.

Signs Warranting Evaluation

In Newborns

  • Swelling of hands and feet
  • Webbed neck appearance
  • Heart murmur detected
  • Feeding difficulties
  • Unusual physical features

In Childhood

  • Height below 3rd percentile
  • Falling off growth curve
  • Frequent ear infections
  • Learning difficulties
  • Social challenges

In Adolescence

  • No breast development by age 13
  • No menstruation by age 15
  • Significant short stature
  • Delayed puberty signs

Regular Monitoring Schedule

Annual Evaluations

  • Growth assessment
  • Blood pressure check
  • Thyroid function tests
  • Hearing evaluation
  • Glucose screening

Periodic Assessments

  • Cardiac imaging (every 3-5 years)
  • Bone density scan
  • Kidney ultrasound
  • Liver function tests
  • Lipid profile

Emergency Situations

  • Chest pain or shortness of breath
  • Severe headache or vision changes
  • Signs of aortic dissection
  • Severe abdominal pain
  • Significant blood pressure elevation

Specialist Referrals

  • Pediatric endocrinologist
  • Cardiologist
  • Reproductive endocrinologist
  • Geneticist/Genetic counselor
  • Psychologist or psychiatrist
  • ENT specialist

Frequently Asked Questions

Can Turner syndrome be inherited?

No, Turner syndrome is not inherited. It occurs as a random error during the formation of reproductive cells or early in fetal development. Parents of a child with Turner syndrome have no increased risk of having another child with the condition. The risk for any pregnancy remains the general population risk of about 1 in 2,500 female births.

What is the life expectancy for someone with Turner syndrome?

With proper medical care, most women with Turner syndrome have a normal or near-normal life expectancy. However, they may have a slightly reduced lifespan (by about 3-10 years) mainly due to cardiovascular complications and other associated conditions. Regular monitoring and treatment of heart conditions, diabetes, and other health issues can significantly improve outcomes and longevity.

Can women with Turner syndrome have children?

Most women with Turner syndrome (95-98%) are infertile due to ovarian dysgenesis. However, about 2-5% may have some ovarian function and can conceive naturally, though pregnancy carries higher risks. Many women with Turner syndrome can become mothers through egg donation and IVF, though pregnancy requires careful monitoring due to cardiovascular risks. Adoption is another option for building a family.

Do all girls with Turner syndrome need growth hormone?

Not all, but most girls with Turner syndrome benefit from growth hormone therapy. Without treatment, average adult height is about 4'8" (143 cm). Growth hormone can add 5-8 cm to final height. The decision depends on the child's growth pattern, predicted adult height, and family preferences. Starting treatment early (ages 4-6) generally produces better results.

How does Turner syndrome affect learning and intelligence?

Most girls and women with Turner syndrome have normal intelligence. However, they may have specific learning differences, particularly with mathematics, spatial relationships, and nonverbal skills. Many excel in verbal areas. With appropriate educational support and accommodations, most complete their education successfully and pursue careers of their choice.

References

  1. Gravholt CH, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome. Eur J Endocrinol. 2017;177(3):G1-G70.
  2. Shankar RK, et al. Turner syndrome: diagnosis and management. Am Fam Physician. 2022;106(2):168-176.
  3. National Organization for Rare Disorders. Turner Syndrome. Updated 2023.
  4. Turner Syndrome Society of the United States. Clinical Practice Guidelines. 2021.
  5. Sybert VP, McCauley E. Turner's syndrome. N Engl J Med. 2004;351(12):1227-38.
  6. Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10-25.