Turner Syndrome

Turner syndrome is a genetic condition affecting women, in which 1 X chromosome is partly or completely missing. The classic result is the karyotype 45,XO with a female phenotype. Turner syndrome is associated with decreased sex hormone levels and is the most common cause of primary amenorrhea Primary Amenorrhea Primary amenorrhea is defined as the absence of menstruation in a girl by age 13 years in the absence of secondary sex characteristics or by the age of 15 years with the presence of secondary sex characteristics. Etiologies can originate in the hypothalamic-pituitary-ovarian (HPO) axis or from anatomic abnormalities in the uterus or vagina. Primary Amenorrhea. Those affected may have a host of medical anomalies involving, but not limited to, the cardiac, renal, reproductive, skeletal, and lymphatic systems. Characteristic appearance is that of a woman with short stature, webbed neck, broad chest with widely spaced nipples, low posterior hairline, and peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of the hands and feet. Genetic testing confirms the diagnosis. Treatment consists of hormone replacement therapy.

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Epidemiology and Genetics

Epidemiology

  • Incidence: 1 in 2,000–2,500 live births 
  • 99% spontaneously abort
  • Most frequent gonadal chromosome anomaly in women

Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics

  • Karyotype: Only 1 normal X chromosome is present; the other is missing or impaired. 
    • Complete sex chromosomal monosomy in approximately 45% of live births: 45,X0 (2nd sex chromosome is missing)
    • Sex chromosomal mosaicism in approximately 50% of live births: 
      • Most commonly 46,XX with 45,X0
      • Approximately 10%–12% have mosaicism involving Y chromosome material.
  • Etiology: 
    • The underlying process is nondisjunction, which may occur during meiosis Meiosis The creation of eukaryotic gametes involves a DNA replication phase followed by 2 cellular division stages: meiosis I and meiosis II. Meiosis I separates homologous chromosomes into separate cells (1n, 2c), while meiosis II separates sister chromatids into gametes (1n, 1c). Meiosis or mitosis:
      • In meiosis Meiosis The creation of eukaryotic gametes involves a DNA replication phase followed by 2 cellular division stages: meiosis I and meiosis II. Meiosis I separates homologous chromosomes into separate cells (1n, 2c), while meiosis II separates sister chromatids into gametes (1n, 1c). Meiosis: Failure of chromosomes ( meiosis Meiosis The creation of eukaryotic gametes involves a DNA replication phase followed by 2 cellular division stages: meiosis I and meiosis II. Meiosis I separates homologous chromosomes into separate cells (1n, 2c), while meiosis II separates sister chromatids into gametes (1n, 1c). Meiosis I) or chromatids ( meiosis Meiosis The creation of eukaryotic gametes involves a DNA replication phase followed by 2 cellular division stages: meiosis I and meiosis II. Meiosis I separates homologous chromosomes into separate cells (1n, 2c), while meiosis II separates sister chromatids into gametes (1n, 1c). Meiosis II) to separate leads to loss of a chromosome (chromosomal monosomy). 
      • In mitosis: Postzygotic nondisjunction leads to different cells within the same individual containing different chromosomal content/karyotypes (chromosomal mosaicism).
    • Nearly 70% of cases are due to meiotic nondisjunction of paternal sex chromosomes; i.e., the paternal X chromosome is lost.
  • No known risk factors

Clinical Presentation

Clinical phenotype

  • Outer appearance
    • Short stature
    • Pterygium colli (webbed neck)
    • Congenital lymphedema
    • “Shield chest”: broad chest with widely spaced nipples
    • Lymphedema on the back of the hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand and foot (sausage-like appearance of fingers and toes)
    • Low hairline
    • Cubitus valgus (outward-turned forearms)
    • Multiple (benign) pigment nevi Nevi Nevi (singular nevus), also known as "moles," are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi
    • Ear anomalies such as low-set or rotated ears
    • Nail dysplasias
    • Short 4th metacarpals/metatarsals
    • Kyphosis and/or scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
  • Cognition/intelligence
    • Intelligence can be normal or reduced.
    • A deficit in some areas can be present (e.g., mathematics, spatial orientation).
  • Behavioral phenotype
    • Increased risk of impaired social skills and/or mood disorders such as anxiety or depression
  • Sex development/fertility
    • Hypergonadotropic hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism
      • Primary ovarian failure as development of ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries typically impaired (streak gonads)
      • Decreased estrogen and progesterone levels with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
    • Delayed or lack of onset of puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty due to lack of estrogen
      • Lack of breast development
      • Primary amenorrhea
    • Infertility
      • Spontaneous pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care very unlikely, but possible in 2%–5% of affected persons

Associated conditions

  • Cardiac abnormalities:
    • Found in approximately ⅓ of individuals with Turner syndrome
    • Congenital bicuspid aortic valve → ↑ risk of aortic stenosis Aortic stenosis Aortic stenosis (AS), or the narrowing of the aortic valve aperture, is the most common valvular heart disease. Aortic stenosis gradually progresses to heart failure, producing exertional dyspnea, angina, and/or syncope. A crescendo-decrescendo systolic murmur is audible in the right upper sternal border. Aortic Stenosis and/or aortic insufficiency
    • Congenital coarctation of the aorta Coarctation of the aorta Coarctation of the aorta is a narrowing of the aorta between the aortic arch and the iliac bifurcation commonly around the point of insertion of the ductus arteriosus. Coarctation of the aorta is typically congenital and the clinical presentation depends on the age of the patient. Coarctation of the Aorta (abnormal narrowing in segment of aorta) 
    • Anomalies of the pulmonary veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins
    • ↑ Risk of aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a "false lumen." Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection (tear occurs in the inner layer of aorta) or rupture; risk goes up during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Malformations of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys and ureters
    • Horseshoe kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys (normal functioning kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys congenitally fused, forming a horseshoe shape)
    • Agenesis, rotational anomalies, obstructions
  • Vision impairments such as color blindness, cataracts, and strabismus Strabismus Strabismus is the misalignment of the eyes while fixating the gaze on an object. Strabismus can be idiopathic, but it may also be caused by cerebral palsy, uncorrected refractive errors, and extraocular muscle or cranial nerve dysfunction. Strabismus (crossed eyes)
  • Hypertension
  • Cystic hygroma (abnormal growth/mass, typically on the neck)
  • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
  • Recurrent otitis media
  • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis and pathologic fractures secondary to ↓ estrogen levels
  • ↑ Risk of gonadoblastoma if Y chromosome material present
Female with turner syndrome

Characteristic features of a girl with Turner syndrome

Image by Lecturio.

Diagnosis and Management

Diagnosis

  • If suspected in utero: 
    • Chorionic villi sampling (CVS)
    • Amniocentesis with karyotype 
  • Postnatal diagnosis:
    • History and clinical examination
    • Genetic testing: Karyotyping confirms the diagnosis.
    • Labs show: ↓ estrogen and androgen levels, ↑ LH and FSH levels
  • Additional screening tests once diagnosis is confirmed:
    • Hearing evaluation
    • Eye exam
    • Neuropsychological, developmental, educational, and behavioral assessments/screenings 
    • Blood pressure measurements in arms and legs
    • Routine labs: thyroid test, lipid screening, glucose screening, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Imaging: 
      • Baseline echocardiogram and/or cardiac magnetic resonance imaging (MRI) to check for cardiac defects
      • Renal ultrasound to check for malformations
      • Baseline dual-energy X-ray absorptiometry (DEXA) scan in early adulthood

Management

  • Hormonal replacement:
    • Estrogen therapy (life long) initiated in adolescence for sexual maturation/development
    • Cyclic progestin therapy to accompany estrogen within 2 years of beginning estrogen therapy and/or breakthrough bleeding begins
    • Human growth hormone to try to improve short stature; used until bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones age reaches 14 years
  • Fertility treatment if children are desired
  • In the rare instance of Y chromosome material being present, gonadectomy is recommended.

Clinical Relevance

Differential diagnosis

The following conditions are differential diagnoses of Turner syndrome:

  • Noonan syndrome: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance genetic condition caused by several potential gene mutations. Both men and women can be affected. Clinical presentation includes short stature, webbed neck, and congenital heart defects. Genetic testing confirms the diagnosis. Individuals with Noonan syndrome have a normal karyotype. Developmental delays are more common than in Turner syndrome. 
  • Gonadal dysgenesis: congenital condition in which the gonads do not develop. Both men and women are affected. Gonadal dysgenesis is not caused by a chromosomal abnormality. Women have a normal 46,XX karyotype with lack of onset of puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty, primary amenorrhea Primary Amenorrhea Primary amenorrhea is defined as the absence of menstruation in a girl by age 13 years in the absence of secondary sex characteristics or by the age of 15 years with the presence of secondary sex characteristics. Etiologies can originate in the hypothalamic-pituitary-ovarian (HPO) axis or from anatomic abnormalities in the uterus or vagina. Primary Amenorrhea, and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility similar to Turner syndrome. The phenotypic features seen in Turner syndrome are not present, however. Therapy with hormone replacement is required.

Related condition

The following condition is related to Turner syndrome as it also causes gonadal insufficiency due to a chromosomal abnormality:

  • Klinefelter syndrome Klinefelter syndrome Klinefelter syndrome is a chromosomal aneuploidy characterized by the presence of 1 or more extra X chromosomes in a male karyotype, most commonly leading to karyotype 47,XXY. Klinefelter syndrome is associated with decreased levels of testosterone and is the most common cause of congenital hypogonadism. Klinefelter Syndrome: chromosomal abnormality disorder seen in men in which extra X and possibly Y chromosomes are present in karyotype. Causes delayed puberty Delayed Puberty Delayed puberty (DP) is defined as the lack of testicular growth in boys past the age of 14 and the lack of thelarche in girls past the age of 13. Delayed puberty affects up to 5% of healthy boys and girls, and half of all cases are due to constitutional growth delay. Delayed Puberty and primary hypergonadotropic hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism in men. Individuals with this condition tend to present as tall, phenotypic men, with small testes, decreased body hair, gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia, and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility. Genetic testing confirms the diagnosis. Requires testosterone replacement therapy.

References

  1. Turner Syndrome. Medline Plus. https://medlineplus.gov/genetics/condition/turner-syndrome/
  2. Morgan, Thomas. (2007). Turner Syndrome: Diagnosis and Management. Am Fam Physician. 76(3):405–417.
  3. Gravholt, C., Andersen et al. on behalf of the International Turner Syndrome Consensus Group. (2017). Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting, European Journal of Endocrinology, 177(3), G1-G70. https://eje.bioscientifica.com/view/journals/eje/177/3/EJE-17-0430.xml
  4. Backeljauw, Philippe. (2020). Clinical manifestations and diagnosis of Turner syndrome. UpToDate. Retrieved Dec 1, 2020 from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-turner-syndrome?search=turner%20syndrome&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details