Turner Syndrome

Introduction to Turner Syndrome

Turner syndrome (TS) is a chromosomal disorder affecting females, characterized by the partial or complete absence of one X chromosome. It occurs in approximately 1 in 2,500 live female births and is associated with a distinct pattern of physical and developmental features.

Key points:

  • Chromosomal karyotype: 45,X or mosaic patterns
  • Affects only females
  • Primary features: short stature and ovarian insufficiency
  • Multisystem disorder requiring lifelong multidisciplinary care

Etiology of Turner Syndrome

Turner syndrome results from the complete or partial absence of the second X chromosome in females. The exact mechanism of X chromosome loss is not fully understood, but it occurs during gametogenesis or early embryonic development.

Chromosomal Variations:

  • Classic 45,X: Complete absence of one X chromosome (40-50% of cases)
  • Mosaicism: Mixture of 45,X and normal 46,XX cell lines (30-40% of cases)
  • Structural abnormalities of X chromosome: Isochromosome Xq, ring X chromosome, or deletions (10-20% of cases)

The phenotypic expression varies depending on the specific chromosomal arrangement and the extent of mosaicism.

Clinical Features of Turner Syndrome

Turner syndrome presents with a wide spectrum of clinical features, varying in severity and combination among affected individuals.

Physical Characteristics:

  • Short stature: Final adult height typically 20 cm below population mean
  • Lymphedema: Often present at birth, affecting hands and feet
  • Neck webbing: Redundant skin at the nape of the neck
  • Low posterior hairline
  • Broad chest with widely spaced nipples
  • Cubitus valgus: Increased carrying angle of the arms
  • Short fourth metacarpal
  • Multiple pigmented nevi

Reproductive System:

  • Gonadal dysgenesis: Leading to primary ovarian insufficiency
  • Delayed puberty or absent pubertal development
  • Infertility in most cases

Cardiovascular System:

  • Congenital heart defects: Bicuspid aortic valve (30%), coarctation of the aorta (10%)
  • Hypertension: Increased risk in adolescence and adulthood
  • Aortic dilation and dissection: Increased lifetime risk

Endocrine System:

  • Hypothyroidism: Increased prevalence of autoimmune thyroiditis
  • Glucose intolerance and type 2 diabetes: Increased risk in adulthood
  • Osteoporosis: Due to estrogen deficiency and other factors

Neuropsychological Features:

  • Normal verbal IQ with possible deficits in nonverbal skills
  • Difficulties with spatial-temporal processing and executive function
  • Increased risk of attention deficit and hyperactivity disorders
  • Social adjustment challenges

Diagnosis of Turner Syndrome

Diagnosis of Turner syndrome can occur at various life stages, from prenatal period to adulthood. A combination of clinical features and genetic testing is used for definitive diagnosis.

Diagnostic Approaches:

  1. Prenatal Diagnosis:
    • Abnormal maternal serum screening
    • Fetal ultrasonography findings (e.g., increased nuchal translucency, cystic hygroma)
    • Non-invasive prenatal testing (NIPT)
    • Confirmatory karyotype through amniocentesis or chorionic villus sampling
  2. Neonatal Diagnosis:
    • Presence of lymphedema, broad chest, or other characteristic physical features
    • Karyotype analysis of peripheral blood
  3. Childhood Diagnosis:
    • Short stature or growth failure
    • Delayed puberty
    • Characteristic physical features
    • Karyotype analysis
  4. Adult Diagnosis:
    • Primary amenorrhea
    • Infertility evaluation
    • Karyotype analysis

Genetic Testing:

  • Standard karyotype: Identifies 45,X and obvious structural abnormalities
  • FISH (Fluorescence In Situ Hybridization): Detects low-level mosaicism
  • Array CGH (Comparative Genomic Hybridization): Identifies subtle X chromosome abnormalities

It's important to note that a 30-cell karyotype is recommended to detect 10% mosaicism with 95% confidence. In cases of strong clinical suspicion with normal 30-cell karyotype, additional genetic testing may be warranted.

Management of Turner Syndrome

Management of Turner syndrome requires a multidisciplinary approach throughout the lifespan, addressing various aspects of health and development.

Key Management Strategies:

  1. Growth Hormone Therapy:
    • Initiated early (around 4-6 years of age)
    • Continues until final adult height is reached
    • Can increase final height by 5-10 cm
  2. Estrogen Replacement Therapy:
    • Initiated around 11-12 years of age for pubertal induction
    • Low-dose estrogen, gradually increased over 2-3 years
    • Progesterone added after breakthrough bleeding or 2 years of estrogen
    • Continued through adulthood for bone health and cardiovascular protection
  3. Cardiovascular Management:
    • Echocardiogram at diagnosis and regular intervals
    • Blood pressure monitoring and management
    • Cardiac MRI in adolescence and adulthood
  4. Reproductive Health:
    • Fertility counseling
    • Consideration of oocyte or embryo cryopreservation in mosaic cases
    • Discussion of assisted reproductive technologies
  5. Bone Health:
    • Ensure adequate calcium and vitamin D intake
    • Weight-bearing exercises
    • DEXA scans to monitor bone mineral density
  6. Psychosocial Support:
    • Regular psychological assessments
    • Educational support for learning difficulties
    • Social skills training if needed
  7. Endocrine Management:
    • Regular thyroid function tests
    • Diabetes screening
    • Management of associated endocrine disorders

Monitoring and Follow-up:

Regular follow-up with a multidisciplinary team is essential, including endocrinologists, cardiologists, gynecologists, and psychologists. Frequency of visits and screenings should be tailored to individual needs and current guidelines.

Complications of Turner Syndrome

Turner syndrome can lead to various complications affecting multiple organ systems. Awareness and early management of these complications are crucial for improving quality of life and long-term outcomes.

Major Complications:

  1. Cardiovascular Complications:
    • Aortic dissection: Increased lifetime risk, especially with bicuspid aortic valve or coarctation
    • Hypertension: Occurs in up to 50% of adults with TS
    • Ischemic heart disease: Increased risk in adulthood
  2. Endocrine and Metabolic Complications:
    • Osteoporosis: Due to estrogen deficiency and other factors
    • Type 2 diabetes: Increased risk, especially in adulthood
    • Autoimmune thyroid disease: Hypothyroidism in up to 30% of patients
    • Celiac disease: Increased prevalence compared to general population
  3. Reproductive Complications:
    • Infertility: In majority of cases due to accelerated follicle atresia
    • Pregnancy complications: Higher risk in those who achieve pregnancy
    • Gonadoblastoma: Increased risk with Y chromosome material
  4. Renal and Urological Complications:
    • Structural renal anomalies: Horseshoe kidney, duplicated collecting system
    • Recurrent urinary tract infections
  5. Otological Complications:
    • Hearing loss: Both conductive and sensorineural
    • Recurrent otitis media
  6. Ophthalmological Complications:
    • Strabismus
    • Ptosis
    • Color blindness (increased prevalence)
  7. Neuropsychological Complications:
    • Learning difficulties, particularly in mathematics and spatial awareness
    • Increased risk of attention deficit disorders
    • Social adjustment challenges
  8. Orthopedic Complications:
    • Scoliosis
    • Hip dysplasia
    • Osteoarthritis

Management of Complications:

  • Regular screening for known complications based on current guidelines
  • Prompt intervention when complications are identified
  • Lifestyle modifications to reduce risk (e.g., maintaining healthy weight, regular exercise)
  • Patient education about potential complications and warning signs
  • Coordinated care among specialists to address multiple system involvement

Prognosis of Turner Syndrome

The prognosis for individuals with Turner syndrome has significantly improved over the past few decades due to advances in medical management and increased awareness. However, it varies depending on the specific features present and the quality of care received.

Factors Influencing Prognosis:

  1. Early Diagnosis and Intervention:
    • Earlier initiation of growth hormone therapy leads to better height outcomes
    • Timely management of associated conditions improves overall health
  2. Cardiovascular Health:
    • Presence and severity of congenital heart defects
    • Effectiveness of blood pressure management
    • Regular cardiovascular monitoring and intervention when needed
  3. Hormonal Management:
    • Adequate estrogen replacement therapy for bone and cardiovascular health
    • Management of other endocrine disorders (e.g., thyroid dysfunction, diabetes)
  4. Psychosocial Support:
    • Access to appropriate educational support
    • Psychological interventions when needed
    • Social integration and support systems
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