Turner Syndrome
Overview
Other Names & Coding
Q96, Turner syndrome
ICD-10 for Turner Syndrome (icd10data.com) provides further coding details for variants of the syndrome.
Prevalence
Genetics
Prognosis
Practice Guidelines
Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE,
Sas TCJ, Silberbach M, Söderström-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF.
Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International
Turner Syndrome Meeting.
Eur J Endocrinol.
2017;177(3):G1-G70.
PubMed abstract
Roles of the Medical Home
Clinical Assessment
Overview
Pearls & Alerts for Assessment
High false positive prenatal resultsAs many as 30% of fetuses suspected of having Turner syndrome based on cytogenetic studies alone may ultimately have normal karyotypes and normal physical exam findings. Prenatal diagnosis of Turner syndrome should always be accompanied by fetal ultrasonography; the likelihood of Turner syndrome is reduced if sonographic results are normal (e.g., no cystic hygroma, renal, or cardiac malformations). [Gravholt: 1996] [Huang: 2002]
Risk of gonadoblastomaAny patient with Turner syndrome who has marker chromosome elements (sex chromosome material of uncertain origin) detected on the karyotype or who develops virilization should be screened for Y chromosome mosaicism. The presence of a Y chromosome can be detected by standard karyotype or PCR (polymerase chain reaction). When Y-chromosome material is present (incidence of 5–12%), prophylactic gonadectomy is recommended due to an increased risk (~10%) of gonadoblastoma. [Binder: 1995] [Gravholt: 2017]
Short stature and Turner syndromeWhile individuals with Turner syndrome may exhibit a constellation of unusual features and organ malformations, short stature and growth failure are the only findings that are present in virtually 100% of patients. [Palmer: 1976]
Aortic dissection and rupture riskThe incidence of acute aortic dissection in young and middle-aged women with Turner syndrome is more than 100 times that of the general population, and the mean age of onset in those with Turner syndrome is 30 years (range 4-64) compared to 71 years. [Bondy: 2008] [Carlson: 2007] Risk factors for dissection include systemic hypertension, aortic dilatation, and aortic valve abnormalities, though only rarely is a predisposing factor identified. Presenting complaints may be vague or minor in nature, such as abdominal pain, "heartburn," back or shoulder pain, or a change in voice (related to traction on the recurrent laryngeal nerve). If persistent, these symptoms should be given serious investigation, including trans-esophageal echocardiography,chest CT, or cardiac MRI.
Screening
For the Condition
Other ultrasound findings such as coarctation of aorta or cardiac defects, intrauterine growth restriction, renal anomalies, brachycephaly, poly or oligohydramnios are further suggestive of Turner syndrome. If the results of fetal ultrasonography are normal, fetal cytogenetic studies have a relatively high false positive rate and non-invasive prenatal testing (NIPT) yields 2.5 as many false positives for Turner syndrome as it does true positives. [Yu: 2017] These results should be considered with caution when counseling a family about the risk of Turner syndrome. Regardless of the test procedure or results, genetic counseling should be provided before and after any prenatal diagnostic procedure. Ultrasound and maternal serum screening are not diagnostic, and karyotype confirmation of Turner syndrome is absolutely needed. Advanced maternal age is not a risk factor for Turner syndrome.
Of Family Members
For Complications
- Annual physical exam, including height, weight, blood pressure, and skin exam
- Comprehensive ophthalmologic exam starting at 12-18 months or at diagnosis
- Audiometric evaluation every 3 years starting at 9-12 months of age
- Scoliosis/orthopedic evaluation annually
- Renal ultrasound at diagnosis
- Cardiovascular:
- Resting EKG and QTc measurement at diagnosis
- Transthoracic echocardiogram (TTE) at diagnosis
- Cardiac MRI (CMR) as soon as feasible without need for general anesthesia
- TTE or CMR (click on charts below for details)
- In the absence of aortic abnormalities, every 5 years
- If hypertension (HTN), bicuspid aortic valve (BAV), coarctation of the aorta (CoV), or Turner syndrome-specific aortic size Z-score (TSZ) >3, yearly
- After 16 years, frequency determined by risk
Cardiac screening in Turner syndrome, infant - 16 yrs.
(from [Gravholt: 2017])
Click image for full-size version.Cardiac screening in Turner syndrome, above 16 yrs.
(from [Gravholt: 2017])
Click image for full-size version.
- Thyroid function tests annually starting at age 4
- Liver function tests annually starting at age 10
- Annual HbA1c, glucose starting at age 10
- Neuropsych evaluation at preschool and school transitions (to high school and higher education)
- Pediatric dental specialist by age 2, orthodontic evaluation no later than age 7
- Dermatology follow up for nevi
- Nutritional evaluation, including celiac screening every 2 years, starting at age 2
- 25-OH vit D level between 9-11 years and every 2-3 years thereafter
Presentations
Presentations of Turner syndrome may include:
- Unexplained growth failure
- Low-set ears
- Micrognathia
- Epicanthal folds
- Nuchal redundancy, cystic hygroma
- Widely spaced nipples, perhaps with shield chest and pectus excavatum
- Lymphedema sequence (edema of hands or feet, webbed neck, low hairline, hyperconvex and hypoplastic nails)
- Cardiac anomalies, such as bicuspid aortic valve, coarctation of aorta
- Cubitus valgus
- Multiple pigmented nevi
- Short fourth metacarpal bones
- Madelung deformity
- Hearing loss
- Elevated FSH
In childhood and adolescence
- Short stature (in nearly 100%)
- Chronic otitis media
- Scoliosis
- Hyperconvex, narrow fingernails; thin,
mildly dysplastic toenails - Pubertal delay
- Ovarian deficiency
Diagnostic Criteria
Additional metaphases may be counted or FISH studies performed if there is suspicion of undetected mosaicism. Although a peripheral blood karyotype is usually adequate, a second tissue, such as skin fibroblasts, buccal mucosa cells, or possibly bladder epithelial cells from the urine, may be examined if there is a strong suspicion of Turner syndrome and the karyotype is normal. Any patient with Turner syndrome who has marker chromosome elements (sex chromosome material of uncertain origin) detected on the karyotype or who develops virilization should be screened for Y chromosome mosaicism. The presence of a Y chromosome can be detected by standard karyotype or FISH (fluorescent in situ hybridization) or PCR (polymerase chain reaction). PCR techniques are more sensitive than FISH in detecting cryptic Y-material. When Y-chromosome material is present (incidence of 5–12%), prophylactic gonadectomy is recommended due to an increased risk (around 10%) of gonadoblastoma. [Binder: 1995] [Gravholt: 2017]
Clinical Classification
- 45, X (monosomy X) is found in approximately 45% of live births with Turner syndrome; these patients should be evaluated for presence of Y chromosome material.
- 45, X mosaicism is a mosaic chromosomal complement (e.g., 45,X/46,XX) detectable in 20-30% of all patients with Turner syndrome.
- X chromosome anomalies:
- Xp or Xq deletion: Some patients have a deletion of the short arm of the X chromosome with or without 45,X cell line mosaicism. Patients with terminal Xq deletion, may not have any other features of Turner syndrome besides ovarian insufficiency.
- Ring chromosome X
- Isochromosome Xq (46,X,i(X)q): Patients with a structurally abnormal X chromosome consisting of 2 copies of the long arm with some intervening short arm or centromeric material are at higher risk for autoimmune disorders.
Differential Diagnosis
Comorbid & Secondary Conditions
- Aorto-cardiac anomalies
- Dyslipidemia
- Renal anomalies
- Hypertension
- Osteopenia
- Hearing loss
- Primary ovarian insufficiency
- Infertility
- Celiac disease
- Hypothyroidism
- Hepatic fibrosis
History & Examination
- In the presence of a single clinical feature such as fetal hydrops or cystic hygroma, unexplained short stature, obstructive left-sided cardiac abnormality (such as a bicuspid aortic valve, coarctation, aortic stenosis, hypoplastic left heart syndrome, or mitral valve abnormalities), delayed puberty, characteristic facial features (such as short broad neck with webbing, micrognathia, low set ears and down-slanted palpebral fissures with epicanthal folds), or infertility
- If 2 or more features commonly associated with Turner syndrome such as renal anomaly (hypoplasia, aplasia or horseshoe kidney), other cardiac anomalies (e.g., partial anomalous pulmonary venous return, atrial or ventricular septal defects), hearing loss, Madelung deformity, dysplastic nails, multiple nevi, and neuropsychological issues associated with short stature are seen in a girl
Current & Past Medical History
Inquire about the following:
- Exercise intolerance, chest, or back pain, which may be a symptom of aortic dilatation or impending rupture
- Acute and chronic otitis media, persistent middle ear effusion, and associated hearing loss
- Problems with vision
- Dental and orthodontic care, tooth abnormalities, dental pain, and difficulty chewing
- Symptoms of hyper- or hypothyroidism, which may indicate the onset of autoimmune thyroiditis
- Intercurrent UTIs, urinary frequency, and urgency (urinary tract infections may increase the risk for chronic renal disease and hypertension)
- Abdominal pain, bloating, flatulence, chronic constipation, or diarrhea, and poor weight gain, which may reflect celiac disease (prevalence of 4-6% in Turner syndrome)
- Chronic abdominal pain, diarrhea, and/or constipation, which may indicate inflammatory bowel disease
- Melena (dark, tarry stools) or blood in the stool, which may indicate the presence of an intestinal vascular malformation
Pregnancy/Perinatal History
Developmental & Educational Progress
Maturationalprogress
Ask about pubertal changes and menstruation in adolescents. While most girls with Turner syndrome do not go through puberty, up to 30% will have some spontaneous pubertal development and 2-5% may become pregnant spontaneously. For those who do experience endogenous ovarian function, discuss birth control, prevention of sexually transmitted disease, and the pregnancy-associated risks of aortic dissection.
Social & Family Functioning
Physical Exam
Vital Signs
Growth Parameters
Height should be plotted on a Turner Syndrome Growth Chart 2-19 Years ( 1.2 MB) beginning at 2 years of age. Growth charts for girls younger than 2 with Turner syndrome have not been developed; in girls younger than 2, height velocity should be monitored on a standard growth chart. Weight and body-mass index (BMI) should be plotted on a standardized BMI chart such as BMI Females 2-20 Years (CDC) ( 68 KB), since no BMI charts for Turner syndrome have been developed.
Skin
HEENT/Oral
Examine for:
- Bitemporal narrowing
- Epicanthal folds and ptosis
- Strabismus
- Low-set, posteriorly rotated, prominent auricles or attached earlobes
- Chronic middle-ear effusion
- Micrognathia (small mandible)
- High, arched palate due to narrow maxilla
- Low posterior hairline
- Pterygium coli (webbed posterior neck)
- Broad, short appearing neck
Chest
Visual inspection may reveal a “shield-shaped” chest with pectus excavatum and widely spaced nipples. Nipples may be hypoplastic and/or inverted.
Heart
A systolic murmur may indicate a left-sided cardiac malformation such as bicuspid aortic valve or aortic coarctation, which may be best heard over the left scapula or in the axilla. Some individuals with these lesions have no auscultatory findings; echocardiography is recommended in all cases of known or suspected Turner syndrome. Absent or weak lower extremity peripheral pulses may indicate aortic coarctation, and an experienced examiner may be able to perceive brachiofemoral delay of the pulses.
Abdomen
Palpate the abdomen for a mass that may signify a renal abnormality such as collecting system malformation with obstruction or horseshoe kidney. Gastrointestinal vascular malformations may present with rectal bleeding and have been reported in individuals 4 months old to 57 years old.
Genitalia
Extremities/Musculoskeletal
Examine for cubitus valgus, short 4th metacarpal bones, Madelung deformity of the wrist, scoliosis/kyphosis, and genu valgum or genu varum. Developmental dislocation of the hip can occur. Radiography may reveal a coarse trabecular pattern, particular at the metaphyses of long bones. Congenital lymphedema may result in residual puffiness of the dorsae of the hands and feet. Fingernails and toenails may be narrow, hyperconvex, and/or deep-set.
Testing
Sensory Testing
Turner syndrome is associated with red-green color blindness (10%), hyperopia (35%), and strabismus (25%) with risk of amblyopia. Girls with Turner syndrome should be evaluated by a pediatric ophthalmologist by 12-18 months of age or earlier if clinically indicated. If initial evaluation is normal, the medical home provider should conduct annual routine vision screening.
Laboratory Testing
If initial diagnosis occurs before 10 years of age:
- Assess thyroid function with a TSH and T4.
- Screen for celiac disease starting at age 2 with a tissue transglutaminase IgA (TTG) and total serum IgA.
- Assess thyroid function with a TSH and T4.
- Screen for celiac disease with a tissue transglutaminase IgA (TTG) and total serum IgA.
- Perform hepatic function panel, GGT, HbA1c with or without fasting plasma glucose, fasting lipid panel.
- 25-hydroxyvitamin D
- Hepatic function panel annually
- Thyroid screening annually with a thyroid-stimulating hormone (TSH) and thyroid hormone (T4)
- Celiac screen every 2 years with a tissue-transglutaminase IgA (TTG-IgA) and a total IgA
- 25-hydroxyvitamin D every 2-3 years
- Fasting lipid panel and HbA1c with or without fasting plasma glucose annually
- Hepatic function panel annually
- Thyroid screen with TSH and T4 annually
- Celiac screen with TTG-IgA and total IgA with suggestive symptoms
- 25-Hydroxyvitamin D every 3-5 years
Imaging
If echocardiography is inadequate, computed tomography or cardiac magnetic resonance imaging should be performed at a center with expertise. Whichever imaging modality is used, it is imperative that the aortic valve leaflets be adequately visualized, along with the aortic arch and descending aorta.
Depending on the cardiac malformation present, periodic echocardiography or cardiac MRI should be performed by a pediatric cardiologist. All individuals with Turner syndrome should undergo cardiac MRI when they are old enough to tolerate the procedure without sedation. Sedation may be required in younger children in whom cardiac MRI is clinically indicated.
In the absence of a bicuspid aortic valve or other significant disease at the initial screening, TTE or cardiac MRI surveillance studies should be performed every 5 years in children, every 10 years in adults, or prior to anticipated pregnancy. The latest consensus guidelines assign girls less than 16 years old with Turner syndrome into low-, moderate-, and high-risk categories based on a Turner syndrome-specific Z-score of the aorta and recommend TTE and pediatric cardiology follow-up every 5 years, 1–2 years, and 6 months-1 year respectively. [Gravholt: 2017]
Renal ultrasound should be performed at the time of diagnosis to identify any presence of urologic abnormalities.
DEXA scan should be done to monitor bone health after adult hormone replacement has been initiated, every 5 years thereafter, and at the discontinuation of estrogen therapy at menopause.
Genetic Testing
Other Testing
Specialty Collaborations & Other Services
Medical Genetics (see NV providers [5])
Genetic Testing and Counseling (see NV providers [11])
Pediatric Cardiology (see NV providers [4])
Pediatric Ophthalmology (see NV providers [6])
Pediatric Otolaryngology (ENT) (see NV providers [5])
Pediatric Dentistry (see NV providers [24])
Developmental - Behavioral Pediatrics (see NV providers [3])
Audiology (see NV providers [8])
Pediatric Gastroenterology (see NV providers [5])
Developmental Assessments (see NV providers [5])
Neuropsychiatry/Neuropsychology (see NV providers [3])
Treatment & Management
Overview
Pearls & Alerts for Treatment & Management
Pregnancy is possible and may come with high risksPregnancy in individuals with Turner syndrome is associated with rare, but potentially fatal, aortic dissection and rupture. While gonadal failure with pubertal delay is common, up to 30% of young women with Turner syndrome will experience some spontaneous pubertal development and 2-5% of women will experience spontaneous pregnancy. When appropriate, prevention of unwanted pregnancy and potential cardiovascular complications of pregnancy should be discussed. Women with Turner syndrome and aortic valve/aortic anomalies should be counseled about the dangers associated with pregnancy and should consult with cardiology so that they can make an informed decision. See the Maturation/Sexual/Reproductive system below for more detail.
Endocrine consultAn endocrine consult should be considered in girls with Turner who have not achieved puberty by 12 years of age.
Estrogen replacementTurner syndrome is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea. Most individuals with Turner syndrome will therefore need hormonal replacement therapy initially for induction of puberty and later for maintaining secondary sexual characteristics, attaining optimal bone mass, normalizing uterine growth (for possible pregnancy later). [Gravholt: 2017]
How should common problems be managed differently in children with Turner Syndrome?
Growth or Weight Gain
Development (Cognitive, Motor, Language, Social-Emotional)
Prescription Medications
Systems
Endocrine/Metabolism
Short stature is the most common finding and is nearly always present, even in patients who do not display other phenotypic characteristics. The etiology of growth failure is poorly understood, but it is thought to involve skeletal dysplasia and poor responsiveness to growth hormone related to haplo-insufficiency for the short stature homeobox-containing (SHOX) gene on the X-chromosome. Growth hormone studies in these patients are typically normal. During infancy and childhood, growth rates are approximately 2 standard deviations below mean growth rates. The adult height of girls not treated with growth hormone is 56 to 57 inches (about 8 inches below the average adult woman's height). Growth hormone secretion pattern is usually normal. Recombinant growth hormone (GH) therapy has been shown to improve adult height in patients with Turner syndrome by 5–8 cm in several studies, but the efficacy is variable and depends on multiple factors including age at initiation, baseline heights, genetic potential, and dose and duration of therapy.
Growth hormone (GH) therapy
Initial consultation with a pediatric endocrinologist should determine the appropriate timing for beginning therapy. The recent guidelines recommend initiating GH treatment early (around 4–6 years of age and preferably before 12–13 years) in the following circumstances:
- The child already has evidence of growth failure (e.g., below 50th percentile height velocity observed over 6 months in the absence of other treatable causes of poor growth).
- The child is already short or has a strong likelihood of short stature (e.g., short parents and short predicted adult height or already pubertal at the time of diagnosis).
Oxandrolone
In girls with Turner syndrome older than 10 years of age with poor projected adult height on GH alone, the addition of oxandrolone, an androgen and anabolic steroid, at 0.03-0.05 mg/kg/day may be considered. [Perry: 2014] [Gravholt: 2017] Oxandrolone may improve adult height by 2-5 cm when used with GH. [Menke: 2010] Potential side effects are less of a concern at the low dosages above, but they may include acne and clitoromegaly. [Perry: 2014]
Autoimmune dysfunction
Autoimmune thyroiditis is common and may be seen as young as 4 years of age. One longitudinal study found that 24% of children over 8 years old with Turner syndrome developed hypothyroidism and 2.5% developed hyperthyroidism. [Livadas: 2005] Because clinical symptoms of thyroid dysfunction rarely manifest, annual screening with FT4 and TSH is recommended starting in early childhood and annually throughout the lifespan. Thyroid replacement should be prescribed in those with hypothyroidism.
Diabetes
The risk of both type 1 and type 2 diabetes mellitus is about a 10-fold and 4-fold increase in patients with Turner syndrome across all ages in epidemiological studies. Obesity, insulin resistance, and impaired glucose tolerance are also common.
Lifelong annual measurement of HbA1c, with or without fasting plasma glucose, is recommended starting at age 10 years. If testing meets criteria for diabetes, the patient should be assessed for antibodies related to type 1 diabetes and be seen by a diabetes specialist.
Dyslipidemia
Dyslipidemia has been reported as young as 11 years and is independent of BMI. Nutrition and exercise counseling are an important component of ongoing care. Regular moderate exercise should be encouraged. Hypercholesterolemia has been reported in 37–50% of women with Turner syndrome. [Garden: 1996]
According to the American Academy of Pediatrics and American Heart Association guidelines, non-fasting, non-HDL cholesterol (calculated by subtracting HDL cholesterol from total cholesterol) should be measured on 2 occasions: once between 9 and 11 years old and again between 17 and 21 years prior to transition to adult care. If non-HDL cholesterol is ≥145mg/ dL (≥3.7mmol/L), then a full fasting lipid profile should be obtained. A lipid profile should be performed in individuals who have at least 1 risk factor for cardiovascular disease starting at age 18 years. [Gravholt: 2017]
Specialty Collaborations & Other Services
Pediatric Endocrinology (see NV providers [6])
Maturation/Sexual/Reproductive
Ovarian insufficiency is a hallmark feature of Turner syndrome. While up to 30% of girls with Turner syndrome have some spontaneous pubertal development, gonadal failure is more common. In many individuals, pubertal delay plays a large role in self-esteem, anxiety, and social isolation. In the past, pubertal induction was delayed until 15 years of age to maximize height potential. Age-appropriate pubertal induction is now recommended to avoid the potential long-lasting psychosocial effects of delayed pubertal development. Pubertal induction should be performed in consultation with an endocrinologist. Serum gonadotropins (especially FSH) should be assessed annually starting at about 11 years, prior to pubertal induction, to exclude the possibility of impending delayed spontaneous puberty. Low levels of anti-Müllerian hormone (AMH) and inhibin B measurements have also been shown to predict ovarian insufficiency, and AMH is perhaps the best indicator of ovarian reserve. If gonadotropins are normal for age, observation for spontaneous puberty is appropriate with future replacement therapy if gonadal failure occurs.
Transdermal 17-β estradiol (TDE) is now the preferred treatment starting around age 11–12 years. It is a more physiologic mode of delivery than oral estrogen and has better bioavailability. Replacement is usually initiated at one-tenth to one-eighth of the adult replacement dose and gradually increased over 2-4 years. Progestin supplementation should be started once withdrawal bleeding is noted or after about 2 years of estrogen therapy to minimize the risk of endometrial cancer due to unopposed estrogen effect. The use of oral contraceptive pills to induce puberty is not recommended because the synthetic estrogen doses are higher than the desired physiologic doses and synthetic progestin may interfere with optimal breast and uterine development. Routine supplementation of very low-dose estrogen in childhood to improve growth or bone mass is currently not recommended. [Shankar: 2018]
Pregnancy
As the patient with Turner syndrome matures, it is important to engage her in discussions about how Turner syndrome and its treatment affect sexual development, function, and reproductive potential. While most women are infertile, 2-5% may become pregnant. Others may achieve pregnancy through various reproductive assistance techniques. Young mosaic Turner syndrome women with persistent ovarian function should be counseled that oocyte cryopreservation after controlled ovarian hyperstimulation is a possible fertility preservation option.
Pregnancy in Turner syndrome is associated with the rare but potentially fatal complication of aortic dissection and rupture. Any woman with Turner syndrome considering pregnancy should have a cardiac evaluation. Other Turner syndrome-related pregnancy complications include hypertension, gestational diabetes, and need for caesarian section due to small maternal size. When appropriate, prevention of sexually transmitted disease and unwanted pregnancy should be addressed. [Bondy: 2007] Women with abnormalities of the aortic valve or aorta should be should be counseled about the dangers associated with pregnancy and should consult with cardiology so that they can make an informed decision. Pregnancy is considered high risk in women with Turner syndrome who have an ascending ASI >2–2.5 cm/m2 due to risk of aortic dissection; assisted reproductive techniques are contraindicated. If pregnancy occurs, it should be managed with strict treatment of pregnancy-associated hypertension, frequent cardiac imaging, and consideration of prophylactic surgery if rapid aortic enlargement is seen. [Shankar: 2018]
Neoplasms
The presence of Y-chromosome material is associated with an approximately 10% risk of gonadoblastoma. [Mazzanti: 2005] [Cools: 2006] Prophylactic removal of gonadal streaks in these individuals is recommended.
Specialty Collaborations & Other Services
Obstetrics & Gynecology (see NV providers [0])
Cardiology
The most serious conditions associated with Turner syndrome involve the cardiovascular system. Congenital heart disease occurs in approximately 22-70% of women with Turner syndrome. [Mortensen: 2012] While left-sided cardiac anomalies are most common, the wider range of malformations includes aortic coarctation (11%), bicuspid aortic valve (15%), partial anomalous pulmonary connection (13%), persistent left superior vena cava (13%), mitral valve abnormalities (<5%), and rarely hypoplastic left heart syndrome. Coarctation may not be detected on echocardiography during infancy but found with the first cardiac MRI. Generalized dilation of major vessels has been described, although the clinical significance of this is unclear. [Lin: 2008]
Individuals with Turner syndrome are at risk for rare but potentially fatal aortic dilation, dissection, and rupture, even in relatively young individuals. The risk for dissecting aortic aneurysm is greater in those with aortic valve abnormalities, coarctation/dilation of the aorta, and systemic hypertension. Counsel at-risk patients and their families about the need for medical monitoring and treatment and the potential symptoms of aortic dissection (chest or back pain). They should also be encouraged to carry medical information at all times to alert medical personnel to the presence of aortic disease. The risk of aortic dissection with pregnancy should be discussed at length with those who have endogenous ovarian function and are considering assisted pregnancy.
Those with CHD diagnosed in childhood may be at risk for postoperative valve re-stenosis, aortic re-coarctation, or residual septal defect shunts and should be monitored closely for the development of new or changing cardiac murmurs. There is a strong association between neck webbing and the presence of a congenital heart defect. Resting tachycardia and a variety of electrocardiographic and repolarization abnormalities have been recognized in Turner syndrome, including prolongation of the QT interval.
The latest consensus guidelines assign girls with Turner syndrome aged <16 years into low-, moderate-, and high-risk categories based on a Turner syndrome-specific Z-score of the aorta and recommend transthoracic echocardiogram (TTE) and pediatric cardiology follow-up every 5 years, 1–2 years, and 6 months-1 year, respectively. In individuals with Turner syndrome over the age of 16 years, the ascending aortic size index (ASI), defined as the aortic diameter in cm corrected for body surface area, is a useful prognostic indicator and, has been used to categorize risk (2–2.3 cm/m2 is moderate risk and >2.3 cm/m2 is high risk) and suggest therapy in the latest guidelines. [Gravholt: 2017] [Shankar: 2018]
Eligibility for competitive sports for individuals with Turner syndrome should be determined by a cardiologist after a comprehensive evaluation. Participation in sports is restricted to low and moderate static and dynamic activities in the moderate risk category while girls in the high-risk category should avoid competitive sports and intense weight training. [Płytycz: 1986]
For patients with no cardiovascular malformation, routine pediatric care should include annual measurement of blood pressure. In the absence of a bicuspid aortic valve or other significant diseases at the initial screening, TTE or cardiac magnetic resonance (CMR) surveillance studies should be performed every 5 years in children, every 5-10 years in adults, or prior to anticipated pregnancy. [Gravholt: 2017] [Bondy: 2007]
The importance of regular moderate exercise should be stressed. Intense or contact activities, as well as isometric exercises, may unnecessarily stress the cardiovascular system.
Hypertension
Half of women with Turner syndrome have hypertension. Although the exact etiology remains unclear, it is possibly due to small-vessel renovascular disease. [Ostberg: 2003] One case series identified coarctation or renal disease as primary causes of hypertension in only 20% of hypertensive Turner syndrome women. [Elsheikh: 2002] Hypertension should be treated aggressively. In individuals without structural heart disease, annual assessment of blood pressure should be performed and medical treatment should be considered if hypertension is present. Medical treatment would include a beta-blocker, an angiotensin receptor blocker, or both to reduce the risk for aortic dissection in women with Turner syndrome who are ≥16 years of age for whom their ascending ASI is ≥2.3cm/m2. [Gravholt: 2017]
Electrocardiographic abnormalities
Every individual with Turner syndrome should receive a resting electrocardiogram (ECG) with QTc measurement at diagnosis. Electrocardiographic and repolarization abnormalities, such as resting tachycardia, right axis deviation, T-wave abnormalities, accelerated AV conduction, and QT-interval prolongation have been described in Turner syndrome. Some changes such as those in P-wave and QTc-dispersion and heart-rate variability in women with Turner syndrome can be attributed to the underlying characteristic autonomic dysfunction. The clinical significance of these observations is unclear. It is recommended, however, that individuals with QT prolongation avoid medications that could further prolong the QT interval. [Bondy: 2007] If they are deemed necessary, ECG should be performed 1–2 weeks after initiation of QT-prolonging drugs.
Coronary artery disease
Coronary artery disease is thought to be twice as common in women with Turner syndrome as in the general population. Risk factors include hypertension, insulin resistance, dyslipidemia, and estrogen deficiency. [Ostberg: 2003]
Specialty Collaborations & Other Services
Pediatric Cardiology (see NV providers [4])
Ears/Hearing
Perform (at least) annual evaluations for middle ear effusions that include pneumatic otoscopy and tympanometry. Otitis media should be treated aggressively because of the significant impact that hearing loss can have on speech and language development and the risk of cholesteatoma formation in those with persistent otorrhea. Persistent middle ear effusion, particularly if associated with language delay or ongoing symptoms of illness, should prompt referral to an otolaryngologist to consider placement of pressure equalization tubes and perhaps tonsillectomy and/or adenoidectomy. Adenoidectomy may, however, exacerbate palatal dysfunction negatively impacting speech quality and should be considered with caution. See the Portal's Hearing Loss and Deafness for management information.
Specialty Collaborations & Other Services
Audiology (see NV providers [8])
Pediatric Otolaryngology (ENT) (see NV providers [5])
Eyes/Vision
Specialty Collaborations & Other Services
Pediatric Ophthalmology (see NV providers [6])
Dental
Patients with cardiac abnormalities should be considered for antibiotic prophylaxis for subacute bacterial endocarditis prior to dental procedures.
Specialty Collaborations & Other Services
Orthodontics (see NV providers [4])
Pediatric Dentistry (see NV providers [24])
Musculoskeletal
Monitor annually for scoliosis during routine pediatric care or every 6 months if on growth hormone therapy. Spinal curvature may progress with rapid growth. While current literature suggests that growth hormone does not cause scoliosis, it may accelerate the development of a spinal curve. Evaluation by an orthopedist is recommended in cases of significant spinal curvature or in those whose curvature is detected at a young age. Management of scoliosis (e.g., bracing or surgical intervention) does not differ from that in the general population. Other muscular complications could include pectus deformities.
Madelung deformity
Madelung deformity results from epiphyseal arrest on ulnar and volar aspects of the distal radius causing the articular surface to be directed toward the ulna and volar aspect of the wrist. This may result in wrist pain as well as limited wrist extension and supination.
Hip dislocation
Developmental dysplasia of the hip occurs with increased frequency. Conservative management with bracing (e.g., a Pavlik harness) or casting is recommended as in the general population with surgical intervention reserved for dysplasia not responsive to bracing.
Cubitus valgus
Increased cubital carrying angle may limit range of motion and interfere with function.
Chronic knee pain
An abnormal tibial plateau coupled with patellar changes may lead to chronic knee pain.
Decreased bone mineral density
Decreased bone mineral density (BMD) with increased fracture risk can occur in older individuals, particularly those not treated with estrogen. Short stature may, however, lead to an underestimation of bone-mineral density by dual-energy x-ray absorptiometry (DEXA). When adjusted for height, women with Turner syndrome who receive appropriate estrogen therapy have an estrogen-independent decrease in cortical BMD with normal trabecular BMD. Causes of low BMD may include non-adherence to estrogen therapy, tobacco use, excessive alcohol use, celiac disease, and/or vitamin D deficiency. The importance of weight-bearing exercise in reaching and maintaining adequate BMD should be discussed with patients and families. Bisphosphonates are not recommended in young women because the reduced cortical BMD is not associated with an increased risk of fractures, and these medications have not been shown to increase cortical BMD. Bisphosphonate use may be considered in women with confirmed osteoporosis, those at risk for fracture, and those who have sustained a low-impact fracture. [Bondy: 2007]
Screen for vitamin D deficiency with a 25-OH vitamin D concentration between 9–11 years and every 2–3 years thereafter. DEXA scans should be obtained to monitor bone health after adult hormone replacement has been initiated, every 5 years thereafter, and at discontinuation of estrogen therapy at menopause. See Osteoporosis and Pathologic Fractures.
Specialty Collaborations & Other Services
Pediatric Orthopedics (see NV providers [8])
Pediatric Endocrinology (see NV providers [6])
Renal
Specialty Collaborations & Other Services
Pediatric Urology (see NV providers [13])
Skin & Appearance
Lymphedema is a major feature of Turner syndrome. The etiology is uncertain, but it is thought to arise from a generalized lymphatic dysplasia. It results in ongoing puffiness of the hands and feet, as well as nuchal webbing, the classic appearance of the chest and atypical configuration of the finger and toenails. Palmar and pedal edema may be exacerbated by estrogen and growth hormone therapy. Symptomatic relief of edema with support socks, elevation, or compression dressings may be required. Chronic diuretic therapy is not recommended as it is marginally effective and may lead to fluid and electrolyte imbalances. Vascular surgery should be avoided. [Bondy: 2007] Patients and families can be directed to The National Lymphedema Network for more information about lymphedema and its management.
Melanocytic nevi
Individuals with Turner syndrome have an increased number of typical melanocytic nevi. Studies conflict about whether Turner syndrome is associated with increased melanoma risk. Therapy with GH may trigger melanocyte growth, but it has been shown neither to increase the number of nevi nor to trigger malignant transformation. Other skin conditions that have a greater prevalence include pilomatricomas, vitiligo, and halo nevi.
Nevi should be monitored for concerning changes in shape, color, and size. It has been suggested that girls and women with Turner syndrome are at increased risk for keloid formation as well, although it is unclear whether this is due to an abnormal healing process or whether this is related to surgeries often involving the head and neck - areas more likely to exhibit keloid formation.
Specialty Collaborations & Other Services
Pediatric Dermatology (see NV providers [1])
Pediatric Plastic Surgery (see NV providers [4])
Gastro-Intestinal & Bowel Function
Feeding problems during infancy are relatively common and may include difficulties latching and sucking, gastroesophageal reflux, and failure to thrive. Anatomical differences in the oropharynx (high palate, palatal insufficiency), oral-motor immaturity, and abnormal gastrointestinal motility may contribute to these problems. Gastroesophageal reflux may safely be treated with H2 receptor blockade or proton pump inhibitors. Nasogastric tube feedings may be required if feeding difficulties are severe. Referral to a speech or occupational therapist for a feeding evaluation may be helpful. In some cases, simple interventions such as elevation of the head after feeds and use of a specialized nipple may result in improvement. [Cassidy: 2005] See the Medical Home Portal's Gastroesophageal Reflux Disease for more information.
Inflammatory bowel disease
Inflammatory bowel disease is 2-3 times more common in Turner syndrome than in the general population, and it has a higher rate of complications when it occurs. Colectomy has been reported in 40% of Turner syndrome-associated inflammatory bowel disease. Other potential complications include fistula formation and sepsis. [Ostberg: 2003] Treatment focuses on nutritional therapy and treatment with anti-inflammatory or immunomodulatory medications.
Celiac disease
Celiac disease affects 4-6% of individuals with Turner syndrome. Celiac disease refers to immune-mediated small bowel inflammation triggered by exposure to the gliadin peptide contained in gluten and found in wheat, barley, rye, and possibly oats. Treatment of celiac disease consists of complete elimination of gluten from the diet and is monitored by clinical response (including growth response), serologic marker response, and small intestinal mucosa histologic response. See the Medical Home Portal's Celiac Disease for more information.
Liver dysfunction
Asymptomatic liver test (ALT, AST, and GGT) abnormalities are a common finding with increasing prevalence with age (20–80%) and an annual incidence of 2.1–3.4%. Liver enzyme elevations tend to persist or progressively increase and rarely revert to normal.
Liver function should be assessed at age 10 and annually thereafter or as clinically indicated. If elevated hepatic enzymes persist for more than 6-12 months, liver ultrasound should be performed to evaluate for hepatic steatosis. If steatosis is not present but elevated hepatic enzymes persist, a hepatology consult should be obtained. Potentially, hepatotoxic medications such as statins and glitiazones should be prescribed with caution in patients with hepatic enzyme elevation. [Bondy: 2007] Structural changes such as fatty infiltration, fibrosis, vascular changes, and nodular hyperplasia have been reported on liver biopsy, but their relationship to liver enzyme elevation has not been defined.
The mechanism of liver disease in Turner syndrome is not well understood, but it is thought to be multifactorial, with obesity and metabolic syndrome as likely contributors. Other possible risk factors include vascular anomalies, as evidenced by nodular regenerative changes, biliary lesions (e.g., primary sclerosing cholangitis) and autoimmunity (e.g., primary biliary cirrhosis). Several studies have now documented improvement or resolution of liver enzyme elevation with estrogen replacement therapy.
Intestinal telangiectasia
Patients with Turner syndrome are at risk for vascular malformations throughout the gastrointestinal tract, which may present with rectal bleeding. Refer to a gastroenterologist for endoscopy and management for persistent rectal bleeding or melanotic stools.
Colonic carcinoma
A few small studies have indicated an increased relative risk of colon cancer in people with Turner syndrome. Current recommendations for colon cancer screening (or treatment) in Turner syndrome are no different from those in the general population.
Specialty Collaborations & Other Services
Pediatric Gastroenterology (see NV providers [5])
Occupational Therapy (see NV providers [22])
Development (general)
Most girls with Turner syndrome will have normal motor, cognitive, and language development, although up to 10% may have developmental delay requiring early intervention or special education. [Sybert: 2004] As girls with Turner syndrome reach school age, a common neurocognitive profile includes lower scores on nonverbal than verbal performance tests. This may result in difficulties with nonverbal abilities, such as math and visual-spatial skills, or difficulties with executive functioning and slower processing speed. These girls may benefit from accommodations in academic testing situations. Despite variable learning difficulties, girls and women with Turner syndrome often have excellent verbal skills and many achieve college-level education.
Specialty Collaborations & Other Services
Developmental - Behavioral Pediatrics (see NV providers [3])
Mental Health/Behavior
Specialty Collaborations & Other Services
General Counseling Services (see NV providers [213])
Educational Testing/Assessment (see NV providers [1])
Transitions
Specialty Collaborations & Other Services
Care for adults with Turner syndrome is ideally delivered in a multidisciplinary setting with endocrinology, gynecology, cardiology, and gastroenterology as needed among other specialties. Specialized Centers of Turner Syndrome Care (TSF) lists such clinics in several states.
Ask the Specialist
When should a child with Turner syndrome begin therapy with growth hormone?
The recent guidelines recommend initiating GH treatment early (around 4–6 years of age and preferably before 12–13 years) if the child already has evidence of growth failure (e.g., below 50th percentile height velocity observed over 6 months in the absence of other treatable cause of poor growth) or if the child is already short or has a strong likelihood of short stature (e.g., short parents and short predicted adult height or already pubertal at the time of diagnosis).
When should an adolescent with Turner syndrome undergo induction of puberty?
In the past, medical induction of puberty with estrogen was delayed until about 15 years of age to maximize a patient's height potential. Recent data indicates that beginning pubertal induction with estradiol at age 11-12 years allows a normal pace of puberty without interfering with the effect of growth hormone on ultimate height. Delaying pubertal induction may have several deleterious effects, including reduced bone mineralization as well as the negative psychosocial consequences of late pubertal development. [Bondy: 2007] Gonadotropins (esp. FSH) should be monitored annually starting at about 11 years to confirm hypergonadotropic hypogonadism prior to pubertal induction. Transdermal 17-beta estradiol is now the preferred treatment starting at around age 11-12 years. [Gravholt: 2017]
Can women with Turner syndrome become pregnant?
While the majority of women with Turner syndrome are infertile, spontaneous pregnancy has been reported. Some women with Turner syndrome become pregnant through assisted reproductive technology. Reports of fatal aortic dissection during pregnancy and the postpartum period have raised concerns about the safety of pregnancy in Turner syndrome. If pregnancy is being considered, a full, preconception cardiac evaluation, including an MRI of the aorta, should be performed. Women who have a repaired cardiovascular defects, bicuspid aortic valve, current aortic dilatation, or systemic hypertension should probably not become pregnant. [Bondy: 2007]
What is the risk of Turner Syndrome recurring in future pregnancies?
The likelihood of a woman having a second child with Turner syndrome is no greater than in the general population.
Resources for Clinicians
On the Web
SHOX Deficiency Disorders (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular
pathogenesis; from the University of Washington and the National Library of Medicine.
Turner Syndrome (GARD)
Includes information about symptoms, inheritance, diagnosis, finding a specialist, related diseases, and support organizations;
Genetic and Rare Diseases Information Center of the National Center for Advancing Translational Sciences.
Helpful Articles
PubMed search for articles on Turner Syndrome in children for the last 3 years.
Shankar RK, Backeljauw PF.
Current best practice in the management of Turner syndrome.
Ther Adv Endocrinol Metab.
2018;9(1):33-40.
PubMed abstract / Full Text
Klein KO, Rosenfield RL, Santen RJ, Gawlik AM, Backeljauw PF, Gravholt CH, Sas TCJ, Mauras N.
Estrogen Replacement in Turner Syndrome: Literature Review and Practical Considerations.
J Clin Endocrinol Metab.
2018;103(5):1790-1803.
PubMed abstract
Levitsky LL, Luria AH, Hayes FJ, Lin AE.
Turner syndrome: update on biology and management across the life span.
Curr Opin Endocrinol Diabetes Obes.
2015;22(1):65-72.
PubMed abstract
Ranke MB.
Why Treat girls with Turner Syndrome with Growth Hormone? Growth and Beyond.
Pediatr Endocrinol Rev.
2015;12(4):356-65.
PubMed abstract
Lee MC, Conway GS.
Turner's syndrome: challenges of late diagnosis.
Lancet Diabetes Endocrinol.
2014;2(4):333-8.
PubMed abstract
Milbrandt T, Thomas E.
Turner syndrome.
Pediatr Rev.
2013;34(9):420-1.
PubMed abstract
Clinical Tools
Care Processes & Protocols
Recommended Approach for Transitioning into Adult Practice, Turner Syndrome (ACPonline) ( 265 KB)
A 3-page clinical guide that lists guidance for the first encounter and ongoing monitoring of the woman with TS who is transitioning
to adult care; American College of Physicians.
Clinical Checklists & Visit Tools
Turner Syndrome Health Maintenance Checklist ( 80 KB)
A checklist with age recommendations for the initial and follow-up screenings of girls (birth - 18 years) with Turner syndrome;
Vana Raman, MD; based on Gravholt et al. Clinical practice guidelines for the care of girls and women with Turner syndrome:
proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017.
Turner Syndrome Care Checklist: Childhood and Adult (TSF) ( 78 KB)
Includes components of care and follow-up in childhood, adolescence, and adulthood; Turner Syndrome Foundation.
Growth/BMI Charts
Turner Syndrome Growth Chart 2-19 Years ( 1.2 MB)
Printable growth chart with curves for girls with and without Turner syndrome; percentiles derived from the National Center
for Health Statistics.
BMI Females 2-20 Years (CDC) ( 68 KB)
Body mass index for age percentiles; Centers for Disease Control.
Medication Guides
Dosing Standards for Estrogen in Turner Syndrome (ACPonline) ( 141 KB)
The overall approach and goals of dosing standards; American College of Physicians.
Questionnaires/Diaries/Data Tools
Clinical Summary & Transfer Record for Young Adults with Turner Syndrome (ACP) ( 363 KB)
Form for sharing information about patients with Turner syndrome preparing for the transition to adult care; American College
of Physicians.
Toolkits
Turner Syndrome Guidelines and Clinical Practice (ES)
Clinical tools for patient assessment, evaluation of transition readiness, dosing standards for estrogen, and clinical summary/transfers;
Endocrine Society.
Turner Syndrome Health Care Guidelines and Checklists (TSSUS) ()
Guidelines, checklists, growth charts, patient education, and other clinical tools related to Turner syndrome; Turner Syndrome
Society of the United States.
Other
Laboratory Guidelines for Turner Syndrome (ACMG)
Provides information on appropriate prenatal and postnatal diagnostic cytogenetic studies for Turner syndrome; American College
of Medical Genetics and Genomics.
Patient Education & Instructions
Turner Syndrome: A Guide for Families (TSSUS) ( 1.4 MB)
A 32-page booklet with information for parents about growth and development, health considerations, and social and emotional
support; Turner Syndrome Society of the United States.
Turner Syndrome Brochure (TSSUS) ( 125 KB)
Two-page brochure providing an overview of Turner syndrome for parents; Turner Syndrome Society of the United States.
Resources for Patients & Families
Information on the Web
Turner Syndrome (Medline Plus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
Turner Syndrome (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
Turner Syndrome (The Magic Foundation)
Information, videos, and a variety of resources; from the Magic Foundation, a non-profit that provides support for families
of children with problems that cause problems with growth.
Turner Syndrome Foundation
Supports research and facilitates education to enhance the care of those affected by Turner syndrome.
Turner Syndrome Society of the United States
A non-profit with chapters and resource groups located throughout the country that provides resources to patients, families,
and physicians for the diagnosis and treatment of Turner syndrome.
Turner Syndrome for Teens (TeensHealth)
A short article to help teens cope with TS; from Nemours.
National & Local Support
Turner Syndrome Society - Local Resource Groups
Links to local groups of the Turner Syndrome Society of the United States in several states, along with frequently asked questions
about the groups, what they offer, and how to develop one.
Turner Syndrome Foundation Resource Map
Interactive map providing information about numbers of women with Turner syndrome in each state and how to connect with resources
via social media.
Studies/Registries
Turner Syndrome, Children (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.
Services for Patients & Families in Nevada (NV)
Service Categories | # of providers* in: | NV | NW | Other states (3) (show) | | NM | RI | UT |
---|---|---|---|---|---|---|---|---|
Audiology | 8 | 3 | 22 | 24 | 22 | |||
Developmental Assessments | 5 | 1 | 105 | 35 | 54 | |||
Developmental - Behavioral Pediatrics | 3 | 1 | 2 | 12 | 9 | |||
Educational Testing/Assessment | 1 | 3 | 2 | 5 | ||||
General Counseling Services | 213 | 1 | 10 | 30 | 279 | |||
Genetic Testing and Counseling | 11 | 5 | 5 | 7 | 10 | |||
Medical Genetics | 5 | 1 | 2 | 4 | 7 | |||
Neuropsychiatry/Neuropsychology | 3 | 1 | 9 | 5 | ||||
Obstetrics & Gynecology | 1 | 6 | 19 | |||||
Occupational Therapy | 22 | 1 | 17 | 22 | 37 | |||
Orthodontics | 4 | 3 | 17 | |||||
Pediatric Cardiology | 4 | 3 | 17 | 4 | ||||
Pediatric Dentistry | 24 | 2 | 6 | 54 | 50 | |||
Pediatric Dermatology | 1 | 1 | 3 | 3 | 2 | |||
Pediatric Endocrinology | 6 | 1 | 4 | 12 | 7 | |||
Pediatric Gastroenterology | 5 | 2 | 18 | 2 | ||||
Pediatric Ophthalmology | 6 | 1 | 6 | 8 | 4 | |||
Pediatric Orthopedics | 8 | 4 | 7 | 16 | 10 | |||
Pediatric Otolaryngology (ENT) | 5 | 1 | 11 | 7 | 10 | |||
Pediatric Plastic Surgery | 4 | 3 | 5 | 4 | 5 | |||
Pediatric Urology | 13 | 1 | 3 |
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Authors & Reviewers
Author: | Vandana Raman, MD |
Reviewer: | Alan F. Rope, MD |
2016: update: Meghan S Candee, MD, MScR |
2011: revision: Vandana Raman, MDA |
2011: update: Alan F. Rope, MDA |
2009: first version: Catherine Jolma, MDA |
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Estrogen Replacement in Turner Syndrome: Literature Review and Practical Considerations.
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Turner's syndrome: challenges of late diagnosis.
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Turner syndrome: update on biology and management across the life span.
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