Turner Syndrome

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Turner Syndrome


Key Points

  • Turner syndrome affects females and presents with characteristic features, most commonly short stature, delayed puberty, webbed neck, shield chest, short fourth metacarpal, and/or nail hypoplasia; infants classically present with transient congenital lymphedema
  • Caused by complete or partial absence of the second sex chromosome in phenotypic females
  • History and physical examination lead to suspicion of Turner syndrome; definitive diagnosis is made with karyotype or other genetic testing
  • Early recognition and diagnosis are essential for appropriate management of growth delay and hypogonadism
  • Treatment includes somatropin to help achieve optimal adult height; low-dose oxandrolone may cause additional growth
  • Estrogen replacement is necessary for most adolescents and adults owing to ovarian failure due to gonadal dysgenesis; most patients are infertile
  • Screening for other associated congenital anomalies is indicated at the time of definitive diagnosis; these include cardiac (aortic coarctation and bicuspid aortic valve) and renal structural abnormalities
  • Risk of aortic dissection necessitates ongoing cardiology evaluation, including monitoring of blood pressure and periodic cardiac imaging
  • Patients with Turner syndrome are at increased risk for certain acquired medical problems, such as osteoporosis and fractures, central obesity and insulin resistance, autoimmune endocrinopathies (eg, hypothyroidism), and hearing loss; ongoing monitoring for acquired disease frequently associated with the syndrome is warranted
  • Final height is improved with somatropin treatment; assisted reproduction techniques can help with infertility
  • Prognosis is generally good; patients do have a 3-fold higher mortality rate than general population, largely owing to increased cardiovascular disease

Urgent Action

  • Urgent cardiology evaluation is indicated for aortic dilation that may lead to aortic dissection
  • Chest pain in patients with Turner syndrome can herald aortic dissection, and care should be taken to exclude this potentially devastating complication


  • Turner syndrome may go unrecognized when short stature is the only presenting symptom
  • Presence of Y chromosome material confers risk for gonadoblastoma, and without resection, gonadoblastoma can transform into malignant neoplasm
  • Hypertension, if unrecognized or untreated, can contribute to aortic dissection
  • Failure to consider aortic dissection in patients with Turner syndrome who present with chest pain
  • Risk of aortic dissection and rupture is further increased in patients who become pregnant
  • Adolescents and young adults with Turner syndrome require care in the transition to ongoing adult medical services because up to 30% of patients discontinue care as adults r1


Clinical Clarification

  • Turner syndrome is characterized by complete or partial absence of the second sex chromosome in females, leading to a broad range of physical features that include short stature, gonadal failure, and cardiovascular disease r2
  • Affects 1 in 2000 to 5000 live-born girls r2


Clinical Presentation


  • Timing of presentation is variable; some patients present in infancy, whereas others present in childhood or adolescence
    • Lymphedema is the most common reason to consider diagnosis during infancy r3c1
    • Short stature is the most common reason to consider diagnosis during childhood and adolescence r3c2c3
    • May go unrecognized when short stature is the only presenting symptom
  • Other common symptoms include:
    • Lack of pubertal development and primary amenorrhea c4c5
    • Secondary amenorrhea c6
    • Problems with attention at school c7
    • Difficulty with math but overall intelligence within the reference range c8
    • Frequent ear infections, especially during toddler years c9c10
  • Prenatal screening findings suggestive of Turner syndrome r2r4
    • Nonspecific findings
      • Fetal edema c11
      • Nuchal cystic hygroma c12
      • Left-sided cardiac defect c13
      • Relatively short limbs c14
    • Abnormal karyotype analysis obtained on amniotic fluid cells or fetal lymphocytes (percutaneous umbilical blood sampling) c15

Physical examination

  • Findings are variable
  • General
    • Congenital transient generalized lymphedema c16
    • Hypertension c17
    • Height less than fifth percentile r5c18
    • Lack of pubertal development c19
    • Webbed neck c20
    • Low hairline c21
    • Shield chest (increased chest diameter) with widely spaced nipples c22c23
    • Heart murmur indicative of left-sided cardiac lesion c24
  • Dysmorphic facial features
    • Flat nasal bridge c25
    • Low-set ears c26
    • High-arched palate c27
    • Ptosis c28
    • Hypertelorism c29
    • Upward slanting palpebral fissures c30
    • Epicanthal folds c31
  • Extremities
    • Edema of hands and feet in infancy c32c33
    • Short fourth metacarpal c34
    • Nail hypoplasia c35
    • Cubitus valgus c36
      • Lateral deviation of the forearm from midline at the elbow joint observable with palms facing forward and arms extended
    • Multiple pigmented nevi c37

Associated congenital anomalies

  • Endocrinologic
    • Short stature
      • Most common finding and may be only physical finding r4
      • Result of SHOX gene expression haploinsufficiency and not hGH deficiency r6c38
    • Gonadal failure
      • Ultimately affects 90% of patients, although 30% have some pubertal development r4c39
      • Caused by ovarian dysgenesis; patients have streak gonads (small amount of connective tissue with either no or few atretic ovarian follicles) c40
  • Cardiac
    • Congenital heart disease (up to 50% of patients) r3r7c41
      • Elongated transverse aortic arch (up to 50% of patients) r8c42
      • Bicuspid aortic valve (30% of patients) r3r7c43
      • Aortic coarctation (10%-18% of patients) r7r9c44
      • Other lesions
        • Aortic stenosis c45
        • Partial anomalous pulmonary venous connection c46
        • Mitral valve prolapse c47
        • Atrial septal or ventricular septal defect c48c49
        • Hypoplastic left side of heart c50
        • Coronary artery abnormalities c51
    • Cardiac conduction and repolarization abnormalities more common in patients with Turner syndrome r10
      • Prolonged QTc c52
      • Accelerated atrioventricular conduction r10c53
      • T-wave abnormalities c54
  • Renal
    • Structural abnormalities (30%-40% of patients) r11r12
      • Collecting-system malformations c55
      • Horseshoe kidney c56
      • Other renal positioning abnormalities c57
  • Ophthalmologic r4
    • Strabismus (25%-35% of patients) r13c58
    • Hyperopia (25%-35% of patients) r13c59
    • Cataracts c60
    • Nystagmus c61
    • Red-green color blindness c62
  • Skeletal
    • Congenital hip dislocation in infants c63
    • Madelung deformity of wrist (carpus curvus) c64

Causes and Risk Factors


  • Caused by loss of all or part of X chromosome, including tip of short arm r5c65
    • 50% of patients have monosomy (45,X) r14c66
    • 20% to 30% of patients have mosaicism r14r15c67
      • 45,X/46,XX
      • 45,X/46,XY
      • 45,X/47,XXX
    • 20% to 30% of patients have structural anomalies of an X chromosome r4
      • Isochromosome X c68
      • Deletions of long or short arm of chromosome X c69
      • Ring chromosome X c70
      • Translocations c71
    • Y chromosome is present in up to 6% of patients with Turner syndrome; an additional 3% of patients have a cryptic marker chromosome, which is sometimes derived from Y chromosome material r15
  • Presence of 45,X cell population without clinical findings is not considered Turner syndrome r4

Risk factors and/or associations

  • Affects only phenotypic females r4c72
  • Short stature and various skeletal anomalies associated with Turner syndrome are in part caused by haploinsufficiency of SHOX gene located on the X chromosome at locus Xp22.33 (OMIM *312865r17) r16

Diagnostic Procedures

Primary diagnostic tools

  • History and physical examination c73
    • Timing of presentation is variable
      • Some patients present in the neonatal period with transient congenital lymphedema and/or a variable constellation of classic physical features associated with the syndrome
      • Others present in childhood with short stature and growth failure
      • Additional patients present in adolescence with delayed puberty and primary amenorrhea
      • Some adults with previously undiagnosed Turner syndrome present with secondary amenorrhea
  • Karyotype testing is necessary for diagnosis c74
  • Obtain baseline screening for associated congenital anomalies at time of diagnosis (eg, renal ultrasonography is recommended at diagnosisr18) c75


  • Karyotype with 30-cell analysis of lymphocytes in metaphase r4c76
    • False-negative peripheral blood lymphocyte analysis can occur; different cell lines in the same patient can carry a different distribution of molecular mosaicism (eg, 46,XX peripheral blood lymphocyte karyotype and 45,X fibroblast karyotype in the same individual) r19
      • In patients with highly suggestive clinical features of Turner syndrome but normal peripheral 30-cell karyotype, obtain skin fibroblast karyotype to exclude Turner syndrome
      • Incidental presence of 45,X cell population without clinical findings is not considered Turner syndrome r10
  • Fluorescence in situ hybridization analysis for Y chromosome material c77
    • Y chromosome material may be present in up to 5% of patients and an additional 3% may have a marker chromosome (a chromosome fragment of X or Y origin) r3
    • Patients with Y chromosome material present are at increased risk of gonadoblastoma, and prophylactic gonadectomy is indicated r3
    • Screen for Y chromosome material if marker chromosome is identified on karyotype analysis or if signs of virilization develop r3
      • Some experts advocate testing all patients with 45,X karyotype for Y chromosome material r15
    • Use fluorescent in situ hybridization analysis with X- and Y-specific DNA probes to evaluate for Y chromosome mosaicism r3

Differential Diagnosis

Most common

  • Noonan syndrome r20c78d1
    • Presents in both boys and girls with short stature, dysmorphic facies with downward slanting palpebral fissures, ptosis, hypertelorism, low-set ears, webbed neck, and congenital heart disease
    • Pubertal development is usually normal in females but may be delayed in males
    • Karyotype is normal
    • Diagnosis based on clinical criteria and genetic testing for mutations associated with Noonan syndrome



  • Promote growth with goal of attaining height within reference range for age, puberty at normal age, and eventual adult height within reference range r4
  • Manage any congenital abnormalities associated with the disease (eg, renal, cardiac, endocrine)
  • Monitor for any disease manifestations commonly associated with the syndrome (eg, hypothyroidism, hearing loss)


Recommendations for specialist referral

  • Multidisciplinary team approach to patient care is optimal at diagnosis, leading tor21 continued coordinated multidisciplinary evaluation every 1 to 2 years after transition to adult care r3
  • Refer all patients to cardiologist for ECG, cardiac imaging (echocardiogram or MRI), and regular cardiology follow-up r3r22
  • Urgently refer to cardiologist for evaluation any patient with aortic dilation that could lead to aortic dissection
  • Refer all patients at time of diagnosis to endocrinologist to address growth and hGH replacement issues, puberty and estrogen replacement issues, thyroid function test abnormalities, and for regular endocrine follow-up r3
  • Refer all patients during adolescence to an obstetrician-gynecologist to discuss risks associated with pregnancy and likelihood of infertility r3
  • Refer to surgeon or urologist for prophylactic gonadectomy if Y chromosome material is present
  • Refer all patients to audiologist for hearing screen at the time of diagnosis and for further audiology screening throughout adulthood
  • Refer to otolaryngologist if patient has recurrent otitis media or hearing loss
  • Refer all patients to ophthalmologist for evaluation of potential eye abnormalities and ongoing monitoring for the development of ocular abnormalities
  • Refer to nephrologist if patient has structural abnormality of kidney or collecting system
  • Refer to orthopedic surgeon if patient develops scoliosis or kyphosis
  • Refer to gastroenterologist for positive celiac screen result, persistently elevated liver function test results, concern for cirrhosis, or clinical suspicion for inflammatory bowel disease
  • Refer to psychologist if patient needs support, especially with social isolation and coping with infertility issues
  • Refer to reproductive endocrinologist to discuss fertility options; patients who achieve pregnancy require care by a high-risk obstetrician owing to risk of worsening aortic dissection and rupture during pregnancy

Treatment Options

Growth promotion

  • Start somatropin treatment as soon as growth failure is identified, usually when child falls below the fifth percentile for height on non–Turner syndrome growth charts r2
  • Most patients start somatropin around age 2 years r2
  • Low-dose adjunct oxandrolone can be used in combination with somatropin in patients aged 8 years and older r23r24

Puberty induction

  • Start estrogen therapy at approximately age 12 years; timing varies depending on when somatropin to optimize height potential was initiated r4
  • Continue estrogen replacement in adulthood for prevention of osteoporosis and to reduce risk for atherosclerosis

Psychological and educational issues

  • Comprehensive psychoeducational evaluation

Monitoring and management of acquired disease frequently associated with the syndrome

  • Gonadectomy for patients with Y chromosome material r18
  • Bacterial endocarditis prophylaxis recommended if an underlying cardiac anomaly is present that places patient at risk for endocarditis based on the American Heart Association guidelines r25r26
    • Most Turner syndrome patients do not fall under the criteria requiring antibiotic prophylaxis unless patient has unrepaired cyanotic congenital heart disease or a prosthetic valve
  • Aggressive control of blood pressure with β-adrenergic blocker, angiotensin receptor blocker, or both, is recommended when aortic dilation is present r3r22
    • Target goal blood pressure is low end of reference range

Drug therapy

  • Somatropin c79
    • Indicated in patients with growth failure r27r28
      • Short stature and various skeletal anomalies associated with Turner syndrome are in part caused by haploinsufficiency of SHOX gene located on the X chromosome at locus Xp22.33 (OMIM #312865r17), usually not a specific deficiency in hGH itself r29
      • Rarely, patients will have concomitant hGH deficiency, as evidenced by lack of hGH secretion following provocative testing; however, in patients with Turner syndrome, the hGH–insulinlike growth factor binding protein axis is disturbed r29
    • Leads to greater final adult stature, decrease in central obesity, improved glucose tolerance, and increase in lean body mass
    • Optimal timing not established r4
      • Treatment is initiated and managed by endocrinologist as soon as growth failure is detected (apparent with decreasing height percentiles on reference growth curve)
      • Continue treatment with somatropin until growth plates have fused and little growth potential remains, usually at bone age of 14 years or older, or growth velocity less than 2 cm/year r3
    • FDA-approved dose
      • Dose is adjusted based on growth response and insulinlike growth factor 1 levels r4
      • Note: Several formulations are available with varying doses
        • Subcutaneous dosage (Genotropin or Omnitrope)
        • Somatropin (Recombinant rhGH) Solution for injection; Children: 0.33 mg/kg subcutaneously per week divided into equal doses given 6 or 7 times/week.
  • Oxandrolone c80
    • A synthetic anabolic steroid can be added as an adjunct to somatropin treatment in patients aged 8 years and older; result is an additional modest increase in final height.r30r23
    • Indicated for patients who are severely short for age, in whom very short adult stature is anticipated, or in whom the growth rate is modest despite good compliance with somatropin treatment. r23
    • Dose is managed and adjusted by an endocrinologist; optimal timing and duration of therapy is unavailable. r23r24
      • Typical dosing
        • Oxandrolone Oral tablet; Female Children and Adolescents: In combination with growth hormone, oxandrolone 0.05 mg/kg/day PO resulted in significant growth acceleration in 1 study.
    • Long-term side effects are unknown; monitor for unacceptable signs of virilization (eg, clitoromegaly and voice deepening) and blood lipid levels. r23
  • Estrogen c81
    • Indicated in patients in whom spontaneous puberty does not occur (most patients with Turner syndrome) or patients who develop premature gonadal failure later in life.
      • High luteinizing hormone and follicle-stimulating hormone levels with low estradiol levels at time of normal puberty indicate gonadal failure.
      • Starting estrogen replacement at age 12 years allows for normal pace of puberty and is unlikely to inhibit somatropin treatment effects on final height. r3r4
      • Estrogen therapy not contraindicated in patients with elevated liver enzymes. r31
        • Benign elevations in liver function test results are common in patients with Turner syndrome and are of unknown significance.
    • Treatment is initiated and managed by endocrinologist.
      • Low dose is recommended initially and gradually increased over 2 to 4 years to reach estradiol levels within the adult reference range. r4
      • Treat until patient reaches age 50 years; decision to continue hormonal replacement is then made on an individual basis. r32
    • Available in multiple forms, including oral, transdermal, and injectable.
      • Transdermal estradiol is preferred owing to lower risk of thrombosis compared with oral estrogen dosing. r3
      • The following are equivalent doses that achieve estradiol levels within the reference range for young women: r4
        • Estradiol Oral tablet; Adult females: 0.5 mg to 2 mg PO once daily continuously; or in cycles of 21 days on and 7 days off. For hypogonadism, women are treated for the period of reproductive life until the time of natural menopause, which maintains feminization and prevents bone loss.
        • Estradiol Transdermal patch - biweekly; Adult females: 1 patch (delivering 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg per day) replaced twice weekly (every 3 to 4 days); start therapy with 0.025 mg/day dose and adjust as needed. Replace patch twice weekly (every 3 to 4 days); give cyclically or continuously. Use lowest effective dose.
        • Estradiol Cypionate Oil for injection; Adult females: For female hypogonadism, the usual dose is estradiol cypionate 1.5 to 2 mg IM every 4 weeks.
  • Progestin c82
    • Start treatment after 2 years of estrogen treatment or when breakthrough bleeding occurs. r4r18
      • Give cyclically 10 days per month; combination oral contraceptive pill is a convenient alternative once adult estrogen doses are reached.

Nondrug and supportive care

Psychological support r4c83

  • Age-appropriate discussions about implications of diagnosis, especially regarding infertility
  • Support to enhance self-esteem and avoid social isolation
    • Local and national Turner syndrome organizations offer patient-oriented materials and support groups

Educational support r4c84

  • Early intervention for dyslexia or attention deficit disorder, which may interfere with academic performance
  • Classroom accommodations to assist with potential visual-spatial issues and slower processing speed

Facilitate transition to adult care r1c85

  • Adolescents and young women with Turner syndrome require care in the transition to ongoing adult medical services given increased risk for cardiovascular disease, osteoporosis, autoimmune disease (eg, celiac disease, hypothyroidism), glucose intolerance, and dyslipidemia r1
    • Up to 30% of patients discontinue care as adults r1
  • Continuation of estrogen replacement therapy is necessary to reduce risks of cardiovascular disease and osteoporosis associated with premature ovarian failure
  • Continued monitoring for adult disease frequently associated with Turner syndrome is warranted

Provide family support and anticipatory guidance c86c87

  • Web-based resources are available r33
Prophylactic gonadectomy c88c89
General explanation
  • Ultrasonography and/or MRI imagingr35 is performed to locate testicular tissue and ovaries; removal is usually accomplished by laparoscopic approach r34
    • Testiclelike gonads can be located in any pelvic anatomic location, usually pelvis, inguinal canal, or labia majora
    • Streak gonads can be located in the ovarian fossa
  • Consider preservation of follicles or oocytes to retain future reproductive potential r10
  • Hysterectomy is not indicated
  • Patients with Turner syndrome who have detectable Y chromosome material in genome (owing to increased risk of gonadoblastoma) r10

Comorbidities c90

Special populations

  • Pregnant patients
    • Turner syndrome is considered a relative contraindication to pregnancy owing to high risk of death in the perinatal period r36
    • Absolute contraindications to pregnancy in patients include either of the following: r3
      • Aortic dilation with a body surface area–adjusted aortic size index greater than 2 cm/m², OR
      • Any significant cardiac abnormality
    • Risk of aortic dissection and rupture is further increased in patients who become pregnant
    • Patients require careful assessment and counseling before considering conception r3
    • Pregnant patients require cautious monitoring for worsening aortic dilation and treatment of any hypertension during pregnancy r3


  • All ages
    • Growth r4c91
      • Plot and follow patient growth on Turner syndrome–specific growth charts beginning at age 2 years r2
      • Patients receiving somatropin treatment require periodic monitoring of insulinlike growth factor 1 levels (at least annuallyr18) and growth parameters as coordinated and managed by endocrinologist
      • Guidelines from 2016 Cincinnati International Turner Syndrome Meeting recommended monitoring growth-promoting treatment by measuring height at least every 4 to 6 months during first year of treatment and at least every 6 months thereafter r18
      • Patients receiving oxandrolone require periodic monitoring for unacceptable adverse effects (signs of virilization including clitoromegaly and voice deepening) and blood lipid levels (decrease in HDL cholesterol) as coordinated and managed by endocrinologist r23
    • Cardiac evaluation
      • Lifelong cardiac follow-up is recommended, even in patients without cardiovascular disease r22
      • Normal cardiovascular system and blood pressure at last assessment
        • Cardiac imaging (echocardiogram or MRI) at appearance of hypertension, transition to adult clinic, or before attempting pregnancy
          • Echocardiogram for younger patients c92
          • MRI for adolescents and adults (when no sedation is needed) c93
        • In absence of issues or transition, cardiac imaging should be done every 5 to 10 years r4
      • Cardiovascular abnormality present or individuals contemplating pregnancy r3
        • Increased frequency of monitoring is recommended, including patients with the following:
          • Patients with aortic dilation (eg, aortic size index greater than 2 cm/m²) r3
          • Patients with an elongated transverse aortic arch
          • Hypertension
        • Frequency of monitoring and treatment should be determined by cardiologist
    • Blood pressure annually c94
    • Otolaryngology and audiology every 1 to 5 yearsr18r4c95c96
    • Strabismus evaluation on physical examination in patients aged 4 months to 5 years r6c97
  • School-aged children r4
    • Liver function tests yearly; starting at age 10 years r18c98
    • Thyroid function tests yearly r18c99
    • Lifelong annual measurement of HbA1c with or without fasting plasma glucose starting at age 10 years r18c100
    • Celiac screen every 2 years r18c101
    • Social skills evaluation at age 4 to 5 years c102
    • Psychoeducational screening yearly c103
      • Includes formal psychoeducational evaluation immediately before starting school (or at diagnosis if later); conduct neuropsychological assessments at key transitional stages in schoolingr18
      • Age-appropriate evaluation for educational/learning deficiencies if indicated by declining school performance
    • Clinical evaluation for scoliosis every 6 months during growth hormone therapy or otherwise annually until growth is completed r18c104
  • Older girls and adults r32
    • Fasting lipids yearly in individuals who have at least 1 risk factor for cardiovascular disease starting at age 18 years r18c105
    • Liver function tests yearly, starting at age 10 years r18c106
    • Lifelong annual measurement of HbA1c with or without fasting plasma glucose, starting at age 10 years r18c107
    • Thyroid function tests yearly r18c108
    • Celiac screen as clinically indicated r18c109
    • Renal function tests yearly c110
    • Evaluation of pubertal development/gonadal function with physical examination and laboratory tests (luteinizing hormone, follicle-stimulating hormone, and estradiol) c111c112c113
    • Bone densitometry (dual-energy X-ray absorptiometry) every 3 to 5 years in adults to monitor bone mineral density after adult hormone replacement therapy has been started and in all patients who are considering estrogen therapy cessationr18c114
    • Age-appropriate evaluation of psychosexual adjustment
    • Clinical evaluation for scoliosis every 6 months during growth hormone therapy or otherwise annually until growth is completed r18

Complications and Prognosis


  • Acquired disease
    • Cardiovascular disease
      • Aortic dissection or rupture c115c116
        • Occurs at median age of 30 to 35 years in 0.6% to 1.4% of patients r3
        • Chest pain in patients with Turner syndrome can herald aortic dissection; take care to exclude this potentially devastating complication
        • Girls or women with aortic dilation and/or bicuspid aortic valve should seek prompt evaluation if they experience acute symptoms consistent with aortic dissection (eg, discomfort in chest, neck, shoulder, back, flank), particularly if onset is sudden and severe r18
        • Usually preceded by aortic dilation c117
          • Patients with aortic size index of 2 to 2.5 cm/m² or more are at highest risk for aortic dissection r3r37
          • Aortic dilation occurs in up to 30% of patients r3
        • Uncommonly (less than 10% of cases) occur without prior risk factors (eg, bicuspid aortic valve, aortic coarctation, hypertension) r3
        • Body surface area–adjusted aortic size index of greater than 2 cm/m² or any significant cardiac abnormality as an absolute contraindication to pregnancy owing to high risk of death from aortic dissection in the perinatal period r3
      • Hypertension c118c119
        • Found in 25% of teens and 40% to 60% of adults r38
        • Idiopathic in many cases r22r32
        • Often systolic and nocturnal r3
        • If unrecognized or untreated, can contribute to aortic dissection r22
      • Dyslipidemia and increased risk for atherosclerosis predisposing to coronary artery disease and cerebrovascular disease r4r22c120c121
      • ECG abnormalities c122c123
        • Common in adults with disease; abnormalities are often independent of structural defects and include the following: r3
          • Right-axis deviation
          • T-wave abnormalities
          • Accelerated AV conduction
          • QTc prolongation
    • Autoimmune
      • Autoimmune thyroid disease
        • Hypothyroidism affects 25% of patients r39c124
        • Hyperthyroidism affects 2.5% of patients r39c125
      • Celiac disease c126
        • Affects 4% to 6% of patients r40
      • Inflammatory bowel disease c127
        • Affects 4% of patients r41
          • Crohn disease c128
          • Ulcerative colitis c129
          • Chronic diarrhea of unknown cause c130
    • Otologic
      • Recurrent otitis media r14c131c132
        • Affects more than half of infants and children with Turner syndrome and may result in conductive hearing loss r14
        • Patients at increased risk for cholesteatoma formation
      • Hearing loss
        • Progressive sensorineural hearing loss in up to 90% of patients by age 45 years r42c133
          • Clinically significant in 60% of those affected; hearing aids required in 27% of patients r42
      • Increased risk of cholesteatoma c134
    • Malignancy
      • Gonadoblastoma c135
        • 5% to 30% risk if Y chromosome material is present r3
        • May transform into malignant germ cell neoplasm r4
        • Prophylactic gonadectomy is recommended in patients with any Y chromosome material in their genome
    • Musculoskeletal
      • Scoliosis affects 10% to 20% of patients r43c136
      • Kyphosis affects up to 50% of patients r44c137
    • Endocrine
      • Metabolic
        • Development of insulin resistance and type 2 diabetes is common r4c138c139
        • Increased frequency of central obesity/abdominal adiposity c140
        • Increased risk of dyslipidemia c141
      • Ovarian failure and fertility c142c143
        • Spectrum of gonadal dysgenesis/hypogonadism is found in Turner syndrome patients r45c144
          • Most have no pubertal development, but up to 30% have spontaneous puberty r4r45
            • Secondary amenorrhea, irregular menstrual cycles, and premature ovarian failure are common among patients who develop spontaneous puberty
          • Spontaneous pregnancy is rare r45
            • Pregnancy-related complications are significant, with a reported 2% or higher risk of death from aortic dissection or rupture during pregnancy r46
            • Pregnancy is possible with oocyte donation and embryo transfer
            • Oocyte preservation is possible in patients with Turner syndrome mosaicism
    • Hepatic disease
      • In patients with Turner syndrome, 44% to 80% have liver function test results outside the reference range r31r47c145
      • Commonly elevated liver enzymes have an unclear relationship with chronic liver disease; if cirrhosis is suspected, refer to a gastroenterologist for further evaluation and management
      • Cirrhosis is 5 times more common in patients with Turner syndrome r48c146
    • Osteoporosis c147
      • Increased risk for developing osteoporosis
        • May be related to previous inadequate estrogen replacement r4
      • Increased risk of fractures
    • Ophthalmologic
      • Congenital and acquired ocular abnormalities are common
    • Dermatologic
      • Increased prevalence of benign pilomatricoma (up to 2.6% of patients) r49c152
        • Pilomatricoma is an otherwise uncommon tumor arising from follicular hair cells
    • Neurocognitive deficits r14
      • Visuospatial organization problems c153
      • Selective nonverbal skill impairments
        • Problems in mathematics c154
      • Psychomotor deficits
      • Attention problems
        • Attention deficit disorder c156
    • Depression r50c157
      • Adolescents and adults with Turner syndrome are at risk; adults seem to have the highest risk
  • Other


  • Mortality is 3 times higher than in the general population due largely to increased cardiovascular disease r51
  • Patients treated with somatropin can achieve adult height within reference range r24
    • Patients treated with somatropin are 7.2 cm taller than untreated group after an average of 5.7 years r27
    • Without somatropin, final adult stature is about 21 cm shorter than healthy female adults r24
    • Health-related quality of life score does not differ between somatropin-treated and untreated groups r52
  • Pregnancy can be achieved through in vitro fertilization with oocyte donation, but risk of death from aortic dissection or rupture during a pregnancy is 2% or higher r46

Screening and Prevention


  • Screening for associated congenital anomalies r4
    • Infants or children diagnosed with Turner syndrome should undergo transthoracic echocardiography at the time of the diagnosis; cardiac magnetic resonance is recommended as soon as feasible without general anesthesia r22
    • Adults diagnosed with Turner syndrome should undergo cardiovascular screening with transthoracic echocardiography and cardiac magnetic resonance at the time of diagnosis r22
    • Cardiac imaging for coarctation of the aorta and other cardiac defects for all patients
      • 4 extremity blood pressure measurements and assessment of peripheral pulse quality c158
      • Cardiac echocardiogram for younger patients c159
      • Cardiac MRI for adolescents and adults (when no sedation is needed) c160
    • ECG for prolonged QTc and other cardiac conduction abnormalities for all patients r22c161
    • Renal ultrasonography for structural abnormalities of kidneys for all patients c162
    • Hearing evaluation by audiologist for all patients c163
    • Eye examination by ophthalmologist for all patients c164
    • Clinical evaluation for hip dislocation for patients aged 0 to 4 years; if examination is inconclusive, obtain plain radiograph of hips to exclude possible subclinical dislocation c165
    • Thyroid function tests with thyroid-stimulating hormone level and free thyroxine level for patients aged 4 years or older c166
    • Celiac screen with tissue transglutaminase IgA antibodies for patients aged 4 years or older c167
    • Educational and psychosocial evaluations for patients aged 4 years or older c168
    • Orthodontic evaluation as clinically indicated for patients aged 7 years or older c169
    • Evaluation of ovarian function with physical examination, luteinizing hormone, follicle-stimulating hormone, and estradiol levels for patients aged 10 years or older c170c171c172
    • Liver function tests and measuring fasting blood glucose, lipids, CBC, creatinine, and BUN for patients aged 10 years or older c173
    • Bone mineral density scan for patients aged 18 years or older c174

Prevention c175

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