Basics
Description
Presence of typical findings in a phenotypic female with complete or partial absence of the second sex chromosome
Epidemiology
Prevalence: 1:2,000 " 5,000 liveborn females
Genetics
- Frequency of genotypes
- 45,X 55%
- 46,Xi(Xq) 17%
- 45,X/46,XX 13%
- 46,Xr(X) 5%
- 45,X/46,XY 5%
- Other 5%
- Recurrence risk is low in subsequent pregnancies in the absence of familial defects of the X chromosome.
Pathophysiology
Deletion of the SHOX gene at Xp22.33 is responsible for the majority of the height deficit in affected patients. Fetuses with Turner syndrome have accelerated loss of germ cells from the second half of gestation through the first few years of life, with eventual gonadal failure.
Associated Conditions
- Short stature (~100%)
- Hypogonadism (90%)
- ADHD (24%)
- Strabismus/hyperopia (17%)
- Conductive hearing loss (21%)
- Sensorineural hearing loss in adults (60%)
- Autoimmune thyroiditis (27%)
- Coarctation of the aorta (11%)
- Bicuspid aortic valve (16%)
- Hypertension (50%)
- Horseshoe kidney (10%)
- Renal collecting system abnormalities (20%)
- Celiac disease (6%)
- Glucose intolerance in adults (40 " 50%)
Diagnosis
History
- Intrauterine growth retardation
- Slow postnatal growth, beginning in infancy
- Lymphedema, especially in infancy
- Frequent otitis media and middle ear effusions
- Normal overall intelligence, with performance IQ less than verbal IQ
- Focused difficulties in math, visuospatial skills, executive functioning
- Decreased social cognition, with problems reading facial expressions, body language, and other nonverbal cues
- Lack of pubertal maturation for age
Physical Exam
- HEENT
- Down slanting palpebral fissures, ptosis, epicanthal folds
- Low set, posteriorly rotated ears
- Arched palate
- Micrognathia
- Neck webbing (pterygium colli)
- Low set posterior hairline
- Musculoskeletal
- Short stature
- Wide carrying angle (cubitus valgus)
- Short 4th metacarpals
- Broad chest relative to height
- Scoliosis
- Genu valgum
- Madelung deformity of wrist
- Other:
- Increased number of pigmented nevi
- Absent breast development, normal pubic hair for age
- Edema of feet and/or hands
- Hyperconvex fingernails, dystrophic toenails
Diagnostic Tests & Interpretation
Laboratory diagnosis of Turner syndrome is based on karyotype. Once the diagnosis is established, additional tests should be performed to identify associated conditions or complications.
Lab
- If older than 4 years old: TSH, free T4, screening for celiac disease
- If older than 10 years old: TSH, free T4, celiac disease serologic screening, LFTs, fasting lipids, CBC, renal function, LH, FSH
Imaging
In all patients, regardless of age: renal ultrasonography and 2-D echocardiography with color Doppler or cardiac MRI
Diagnostic Procedures/Other
- EKG
- Audiologic evaluation
- Orthodontic assessment
- Educational/psychosocial evaluation
- Scoliosis screening
Treatment
General Measures
- Treatment of girls with Turner syndrome focuses on promoting linear growth and pubertal maturation as well as screening for and managing other associated conditions.
- Spontaneous puberty, manifested as breast development, occurs in 14% of girls with a 45,X karyotype and 32% of girls with other Turner syndrome karyotypes. Up to 50% of those with spontaneous puberty may go on to have menses that persist into late adolescence or early adulthood.
- Nearly all girls with Turner syndrome eventually have ovarian failure.
Medication
- Growth hormone administration is part of standard care for girls with Turner syndrome.
- Treatment should start when growth failure is recognized.
- Recommended dose for girls with Turner syndrome is 54 mcg/kg/24 h or 0.375 mg/kg/week.
- Addition of oxandrolone, a nonaromatizable androgen, may be considered in girls older than age 9 years to help promote growth.
- This treatment may accelerate pubic and axillary hair growth, so oxandrolone is generally reserved for peripubertal patients.
- The recommended dose is 0.05 mg/kg/24 h or less.
- Estrogen is required for pubertal-aged girls without spontaneous breast development who have elevated FSH levels.
- Induction of puberty may be delayed to accrue additional linear growth, but early diagnosis and treatment with growth hormone may normalize height and allow for estrogen treatment at a physiologic age.
- There are many estrogen treatment regimens available, including oral and transdermal routes. Treatment is usually initiated at doses that are 1/8 " 1/10 of the adult doses.
- Doses are gradually increased to adult values over 2 " 4 years. After 2 " 4 years, intermittent progestin treatment is given to induce menstrual bleeding.
Additional Treatment
Associated conditions may require treatment, including antihypertensives, SBE prophylaxis, levothyroxine, gluten-free diet, myringotomy tubes, and strabismus care.
Ongoing Care
Follow-up Recommendations
- Age 4 " 5 years
- Assessment of social skills, psychoeducational evaluation prior to school entry
- Age 5 " 12 years
- Every year: BP, TSH, LFTs, educational and social progress
- Every 1 " 5 years: audiology and ENT
- Every 2 " 5 years: celiac disease screening
- As needed: dental and orthodontic evaluations
- Age 12 years " adult
- Every year: BP, TSH, LFTs, fasting lipids, blood glucose
- Every 1 " 5 years: audiology and ENT
- Assessment of pubertal development and psychosexual adjustment
- Every 5 " 10 years: cardiac MRI
- As needed: celiac disease screening
Prognosis
- Height percentile at diagnosis is highly predictive of adult height if not treated with growth hormone or estrogen, with a correlation coefficient of 0.95.
- Height loss in untreated girls with Turner syndrome is approximately 20 cm compared to the midparental target height.
- Mean adult height in untreated girls is 144 cm.
- The presence of webbed neck (pterygium colli) on physical exam is predictive of both aortic coarctation and ovarian failure.
- 90% of women with Turner syndrome have ovarian failure.
- 40 " 50% of adults with Turner syndrome have insulin resistance or abnormal glucose tolerance.
- Girls and women with Turner syndrome have an increased risk for depression, anxiety, and social withdrawal.
Alert
Girls and women with Turner syndrome are at increased risk for aortic dissection, manifested as chest or back pain. Those with a bicuspid aortic valve or with an ascending aortic size index >2.5 cm/m2 are at highest risk.
Additional Reading
- Bondy CA, Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10 " 25. [View Abstract]
- Carlson M, Airhart N, Lopez L, et al. Moderate aortic enlargement and bicuspid aortic valve are associated with aortic dissection in Turner syndrome: report of the international Turner syndrome aortic dissection registry. Circulation. 2012;126(18):2220 " 2226. [View Abstract]
- Davenport ML. Approach to the patient with Turner syndrome. J Clin Endocrinol Metab. 2010;95(4):1487 " 1495. [View Abstract]
- Davenport ML, Crowe BJ, Travers SH, et al. Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial. J Clin Endocrinol Metab. 2007;92(9):3406 " 3416. [View Abstract]
- Devernay M, Ecosse E, Coste J, et al. Determinants of medical care for young women with Turner syndrome. J Clin Endocrinol Metab. 2009;94(9):3408 " 3413. [View Abstract]
- Donaldson MD, Gault EJ, Tan KW, et al. Optimising management in Turner syndrome: from infancy to adult transfer. Arch Dis Child. 2006;91(6):513 " 520. [View Abstract]
- Gault EJ, Perry RJ, Cole TJ, British Society for Paediatric Endocrinology and Diabetes. Effect of oxandrolone and timing of pubertal induction on final height in Turner 's syndrome: randomised, double blind, placebo controlled trial. BMJ. 2011;342:d1980. [View Abstract]
- Kim HK, Gottliebson W, Hor K, et al. Cardiovascular anomalies in Turner syndrome: spectrum, prevalence, and cardiac MRI findings in a pediatric and young adult population. Am J Roentgenol. 2011;96(2):454 " 460. [View Abstract]
- Pinsker JE. Clinical review: Turner syndrome: updating the paradigm of clinical care. J Clin Endocrinol Metab. 2012;97(6):E994 " E1003. [View Abstract]
- Ross JL, Quigley CA, Cao D, et al. Growth hormone plus childhood low-dose estrogen in Turner 's syndrome. N Engl J Med. 2011;364(13):1230 " 1242. [View Abstract]
- Schoemaker MJ, Swerdlow AJ, Higgins CD, United Kingdom Clinical Cytogenetics Group. Mortality in women with Turner syndrome in Great Britain: a national cohort study. J Clin Endocrinol Metab. 2008;93(12):4735 " 4742. [View Abstract]
Codes
ICD09
ICD10
- Q96.9 Turner 's syndrome, unspecified
- Q96.0 Karyotype 45, X
- Q96.1 Karyotype 46, X iso (Xq)
- Q96.3 Mosaicism, 45, X/46, XX or XY
- Q96.2 Karyotype 46, X w abnormal sex chromosome, except iso (Xq)
- Q96.4 Mosaic, 45, X/other cell line(s) w abnormal sex chromosome
- Q96.8 Other variants of Turner 's syndrome
SNOMED
- 38804009 Turner syndrome (disorder)
- 205687000 karyotype 46, X with abnormal sex chromosome except iso (Xq) (disorder)
- 205686009 Karyotype 46, X iso (Xq) (disorder)
- 302960008 Mosaicism 45, X; 46, XX (disorder)
FAQ
- Q: Are older parents at increased risk to have a child with Turner syndrome?
- A: No. Turner syndrome is not associated with either advanced maternal or paternal age.
- Q: Are there special precautions for girls with bicuspid aortic valve?
- A: Affected patients with bicuspid aortic valves should receive SBE prophylaxis.
- Q: Can assisted reproductive technology allow women with Turner syndrome to carry a pregnancy?
- A: In vitro fertilization of donor oocytes has been performed in women with Turner syndrome. However, pregnant women with Turner syndrome have a significantly increased risk for hypertension and gestational diabetes. Importantly, they also are at high risk for aortic dissection. Thus, pregnancy is controversial and usually discouraged at this time.