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Turner Syndrome
Updated: Oct 23, 2009
Introduction
Background
In 1938, Henry Turner first described Turner syndrome, which is one of the most common chromosomal abnormalities.1 More than 95% of adult women with Turner syndrome exhibit short stature and infertility.
A patient with Turner syndrome is shown. This posterior view shows a low hairline and a shield-shaped chest. Note the narrow hip development.
Lymphedema of the feet in an infant is shown. The toes have the characteristic sausagelike appearance.
Hyperconvex nails in Turner syndrome. Note U-shaped cross section.
Pathophysiology
Turner syndrome is caused by the absence of one set of genes from the short arm of one X chromosome. In patients with 45,X karyotype, about two thirds are missing the paternal X chromosome. In addition to monosomy X, a similar clinical picture is found with a 46,XXiq karyotype and in some individuals with mosaic karyotypes. A deletion of the SHOX gene can cause a similar skeletal phenotype known as Leri-Weill dyschondrosteosis.
Frequency
United States
The frequency is approximately 1 in 2000 live-born female infants.2 As many as 15% of spontaneous abortions have a 45,X karyotype.
International
The incidence is the same as in the United States. No known ethnic or racial factors influence frequency.
Mortality/Morbidity
Mortality may be increased in the neonatal period because of coarctation of the aorta and in adulthood because of cardiovascular disease, particularly aortic dissection. Obesity, with associated diabetes mellitus and hypertension, can also contribute to early mortality. Limited epidemiologic studies suggest that life expectancy is reduced by about 10 years. Osteoporosis is common.
Renal anomalies found in some individuals may cause a predisposition to urinary tract infections or hypertension. Even in the absence of cardiac or renal anomalies, patients are prone to develop hypertension.
Individuals with mitral valve disease or aortic valve disease require subacute bacterial endocarditis (SBE) prophylaxis.
Race
No racial or ethnic predilections are known.
Sex
Turner syndrome only occurs in females.3 Noonan syndrome, sometimes inappropriately called male Turner syndrome, can occur in males or females. It is an autosomal dominant genetic disorder and is not a chromosomal disorder. It is unrelated to Turner syndrome.
Age
As a chromosomal disorder, Turner syndrome is present at conception or following the first cell division and remains throughout life. Gonadotropin levels, particularly follicle-stimulating hormone (FSH) levels, may be elevated at birth, although not reliably enough for use in excluding the diagnosis. They are gradually suppressed by about age 4 years, only to rise to menopausal levels after age 10 years.
Clinical
History
- Patients with Turner syndrome should be investigated for the presence of Y chromosomal material using a Y-centromeric probe. These patients may have malignant gonadoblastomas or testicular tissue.4 The presence of virilization requires a thorough search for gonadal, adrenal, or midline tumors.
- Older individuals may have a history of swollen hands and feet at birth.
- Children usually present with short stature, but some girls younger than 11 years have heights within the normal range. Although the presence of other features may increase the index of suspicion, a karyotype is indicated in any girl with unexplained short stature.
- In older adolescents and adults, presenting symptoms usually involve issues of puberty and fertility as well as short stature. Adrenarche, the beginning of pubic hair growth, occurs at a normal age and is not an indication that puberty will progress normally. Breast development is absent when ovarian failure occurs before puberty. Some girls have spontaneous breast development or menses. Diagnosis should be considered in individuals with primary or secondary amenorrhea and in adult women with unexplained infertility, particularly when such individuals also are short in stature.
Physical
Approximately 95% of individuals with Turner syndrome have both short stature and signs of ovarian failure upon physical examination.
- Short stature: In adults, short stature is due to both a slightly slower growth rate in childhood and to an essentially absent adolescent growth spurt. Before age 11 years, some girls have height and growth rates that are well within the normal range, but heights are below the 50th percentile for girls without Turner syndrome.5
- Ovarian failure: Suspect ovarian failure in girls who have no breast development by age 12 years or who have not started menses by age 14 years. Elevated levels of luteinizing hormone (LH) and FSH confirm ovarian failure.
- Pubic hair: Pubic hair development is normal.
- Nails: Many patients have hypoplastic or hyperconvex nails. Although these are not a clinical problem, they are rarely seen in other patients.
- Nevi: Excessive numbers of nevi, when compared to other family members, are common. These may be removed if rubbed or irritated by clothing, but an increased risk of keloid formation is noted.
- Webbed neck: Lymphedema in utero can cause a broad neck and a low or indistinct hairline.
- Cubitus valgus (increased carrying angle): This is a common skeletal anomaly in girls due to abnormal development of the trochlear head. Other anomalies include Madelung deformities and short fourth and fifth metacarpals and metatarsals.
- Short fourth metacarpal or metatarsal: Although this finding is of minimal clinical significance, it can be a clue to the presence of Turner syndrome.
- Shield chest: The chest appears to be broad with widely spaced nipples. This may be caused in part by a short sternum.
- Lymphedema: Lymphedema may be present at any age and is one finding that can suggest Turner syndrome on fetal ultrasonography. Lymphedema is the cause of other anomalies, such as the webbed neck and low posterior hairline. In infants, the combination of dysplastic or hypoplastic nails and lymphedema gives a characteristic sausagelike appearance to the fingers and toes.
- Eye: Ptosis, strabismus, amblyopia, and cataracts are more common in girls with Turner syndrome. Epicanthal folds can be present. Red-green color blindness is an X-linked condition and is believed to occur in girls with Turner syndrome as commonly as it does in males.
- Ears: Serous otitis media is more common, probably due to poor anatomic drainage of the middle ear, which may be associated with a high-arched palate.6 The auricles may be posteriorly rotated or low set as a result of lymphedema. Hearing loss due to otosclerosis is common in adults.
- GI bleeding: This is usually due to intestinal vascular malformations, but the incidence of Crohn disease and ulcerative colitis is also increased.
- Hip dislocation: Infants have a higher incidence of congenital hip dislocation. They should be evaluated clinically and referred for further treatment, if needed.
- Scoliosis: This occurs in 10% of adolescent girls with Turner syndrome and may contribute to short stature. Scoliosis screening is essential.
- Hypertension: Blood pressure elevations may be caused by coarctation of the aorta or renal anomalies but often occur even in the absence of such findings. Blood pressure should be routinely monitored and measured at each medical visit. Four-limb blood pressures should also be evaluated because of the concern of coarctation.
- Murmurs: Cardiovascular malformations include coarctation of the aorta, bicuspid aortic valve, and aortic dissection in adulthood. All individuals should have an initial evaluation and periodic follow-up care from a cardiologist.7 Evaluation prior to initiation of estrogen therapy or assisted reproduction is strongly recommended.
- Thyroid: As many as half of patients have positive antithyroid antibodies, and 10-30% develop hypothyroidism.8 This is often associated with thyroid enlargement.
- Cutis laxa: Loose folds of skin, particularly in the neck, are signs in newborns. This is a result of resolving lymphedema and occasionally is observed after infancy.
- Prenatal signs
- Most concepti with a 45,X karyotype spontaneously abort. Most, if not all, of those who survive to birth are suspected to have mosaicism for a normal cell line.
- Turner syndrome may be prenatally diagnosed by amniocentesis or chorionic villous sampling. Obtain a karyotype by one of these methods if ultrasonography of a fetus reveals a nuchal cystic hygroma,9 horseshoe kidney, left-sided cardiac anomalies, or nonimmune fetal hydrops. A postnatal karyotype may be performed instead of amniocentesis or chorionic villus sampling and is also recommended if the human chorionic gonadotropin (HCG), estradiol, or alpha-fetoprotein (AFP) level is elevated during pregnancy.
- Neonatal pedal edema suggests a diagnostic evaluation for Turner syndrome.
Causes
The diagnosis of Turner syndrome requires the presence of typical phenotypic features and the complete or partial absence of a second sex chromosome.
- Advanced maternal age is not associated with an increased incidence.
- In patients with a single X chromosome, the chromosome is of maternal origin in two thirds of cases.
- Many of the features of Turner syndrome, including the short stature, are due to the lack of a second SHOX gene, which is on the X chromosome.
More on Turner Syndrome |
 Overview: Turner Syndrome |
| Differential Diagnoses & Workup: Turner Syndrome |
| Treatment & Medication: Turner Syndrome |
| Follow-up: Turner Syndrome |
| Multimedia: Turner Syndrome |
| References |
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References
Turner HH. A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology. 1938;23:566-574.
Donaldson MD, Gault EJ, Tan KW, Dunger DB. Optimising management in Turner syndrome: from infancy to adult transfer. Arch Dis Child. Jun 2006;91(6):513-20. [Medline].
[Guideline] Bondy CA. Care of girls and women with Turner syndrome: A guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. Jan 2007;92(1):10-25. [Medline].
Bianco B, Lipay MV, Melaragno MI, Guedes AD, Verreschi IT. Detection of hidden Y mosaicism in Turner's syndrome: importance in the prevention of gonadoblastoma. J Pediatr Endocrinol Metab. Sep 2006;19(9):1113-7. [Medline].
Lyon AJ, Preece MA, Grant DB. Growth curve for girls with Turner syndrome. Arch Dis Child. Oct 1985;60(10):932-5. [Medline].
Sculerati N, Ledesma-Medina J, Finegold DN, Stool SE. Otitis media and hearing loss in Turner syndrome. Arch Otolaryngol Head Neck Surg. Jun 1990;116(6):704-7. [Medline].
Frias JL, Davenport ML. Health supervision for children with Turner syndrome. Pediatrics. Mar 2003;111(3):692-702. [Medline].
Pai GS, Leach DC, Weiss L, Wolf C, Van Dyke DL. Thyroid abnormalities in 20 children with Turner syndrome. J Pediatr. Aug 1977;91(2):267-9. [Medline].
Alpman A, Cogulu O, Akgul M, et al. Prenatally Diagnosed Turner Syndrome and Cystic Hygroma: Incidence and Reasons for Referrals. Fetal Diagn Ther. Mar 12 2008;25(1):58-61. [Medline].
Davenport ML, Crowe BJ, Travers SH, Rubin K, Ross JL, Fechner PY, et al. Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial. J Clin Endocrinol Metab. Sep 2007;92(9):3406-16. [Medline].
Backeljauw P. Does growth hormone therapy before 4 years of age enhance the linear growth of girls with Turner's syndrome?. Nat Clin Pract Endocrinol Metab. Feb 2008;4(2):78-9. [Medline].
Bolar K, Hoffman AR, Maneatis T, Lippe B. Long-term safety of recombinant human growth hormone in turner syndrome. J Clin Endocrinol Metab. Feb 2008;93(2):344-51. [Medline].
Stephure DK. Impact of growth hormone supplementation on adult height in turner syndrome: results of the Canadian randomized controlled trial. J Clin Endocrinol Metab. Jun 2005;90(6):3360-6. [Medline].
Bender B, Puck M, Salbenblatt J, Robinson A. Cognitive development of unselected girls with complete and partial X monosomy. Pediatrics. Feb 1984;73(2):175-82. [Medline].
Foudila T, Soderström-Anttila V, Hovatta O. Turner's syndrome and pregnancies after oocyte donation. Hum Reprod. Feb 1999;14(2):532-5. [Medline]. [Full Text].
Garden AS, Diver MJ, Fraser WD. Undiagnosed morbidity in adult women with Turner's syndrome. Clin Endocrinol (Oxf). Nov 1996;45(5):589-93. [Medline].
Lin AE, Lippe B, Rosenfeld RG. Further delineation of aortic dilation, dissection, and rupture in patients with Turner syndrome. Pediatrics. Jul 1998;102(1):e12. [Medline]. [Full Text].
Hovatta O. Pregnancies in women with Turner's syndrome. Ann Med. Apr 1999;31(2):106-10. [Medline].
Kaneko N, Kawagoe S, Hiroi M. Turner's syndrome--review of the literature with reference to a successful pregnancy outcome. Gynecol Obstet Invest. 1990;29(2):81-7. [Medline].
Carr RF, Ochs RH, Ritter DA, Kenny JD, Fridey JL, Ming PM. Fetal cystic hygroma and Turner's syndrome. Am J Dis Child. Jun 1986;140(6):580-3. [Medline].
Chorazy PA, Himelhoch S, Hopwood NJ, Greger NG, Postellon DC. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics. Jul 1995;96(1 Pt 1):148-50. [Medline].
Davenport ML, Punyasavatsut N, Stewart PW, Gunther DF, Savendahl L, Sybert VP. Growth failure in early life: an important manifestation of Turner syndrome. Horm Res. 2002;57(5-6):157-64. [Medline].
Elsheikh M, Conway GS, Wass JA. Medical problems in adult women with Turner's syndrome. Ann Med. Apr 1999;31(2):99-105. [Medline].
Even L, Cohen A, Marbach N, Brand M, Kauli R, Sippell W, et al. Longitudinal analysis of growth over the first 3 years of life in Turner's syndrome. J Pediatr. Oct 2000;137(4):460-4. [Medline].
Fryer SL, Kwon H, Eliez S, Reiss AL. Corpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndrome. Dev Med Child Neurol. May 2003;45(5):320-4. [Medline].
Gravholt C. Clinical Practice in Turner Syndrome. Nature Clinical Practice Endocrinology & Metabolism. 2005;1:41-52.
Gravholt CH, Juul S, Naeraa RW, Hansen J. Morbidity in Turner syndrome. J Clin Epidemiol. Feb 1998;51(2):147-58. [Medline].
Hasle H, Olsen JH, Nielsen J, Hansen J, Friedrich U, Tommerup N. Occurrence of cancer in women with Turner syndrome. Br J Cancer. May 1996;73(9):1156-9. [Medline].
Health supervision for children with Turner syndrome. American Academy of Pediatrics. Committee on Genetics. Pediatrics. Dec 1995;96(6):1166-73. [Medline].
Lippe BM. Primary Ovarian Failure. In: Clinical Pediatric Endocrinology. 1990. Philadelphia, Pa: WB Saunders; 325-366.
Mazzanti L, Prandstraller D, Tassinari D, Rubino I, Santucci S, Picchio FM, et al. Heart disease in Turner's syndrome. Helv Paediatr Acta. Aug 1988;43(1-2):25-31. [Medline].
Medeiros CC, Marini SH, Baptista MT, Guerra G Jr, Maciel-Guerra AT. Turner's syndrome and thyroid disease: a transverse study of pediatric patients in Brazil. J Pediatr Endocrinol Metab. Apr 2000;13(4):357-62. [Medline].
Natowicz M, Kelley RI. Association of Turner syndrome with hypoplastic left-heart syndrome. Am J Dis Child. Feb 1987;141(2):218-20. [Medline].
Neumann PJ, Gharib SD, Weinstein MC. The cost of a successful delivery with in vitro fertilization. N Engl J Med. Jul 28 1994;331(4):239-43. [Medline].
Price WH, Clayton JF, Collyer S, De Mey R, Wilson J. Mortality ratios, life expectancy, and causes of death in patients with Turner's syndrome. J Epidemiol Community Health. Jun 1986;40(2):97-102. [Medline].
Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, van Teunenbroek A, Hokken-Koelega AC, Waelkens JJ, et al. Final height in girls with Turner's syndrome treated with once or twice daily growth hormone injections. Dutch Advisory Group on Growth Hormone. Arch Dis Child. Jan 1999;80(1):36-41. [Medline]. [Full Text].
Soriano-Guillen L, Coste J, Ecosse E, Léger J, Tauber M, Cabrol S, et al. Adult height and pubertal growth in Turner syndrome after treatment with recombinant growth hormone. J Clin Endocrinol Metab. Sep 2005;90(9):5197-204. [Medline]. [Full Text].
Starke M, Albertsson Wikland K, Möller A. Parents' descriptions of development and problems associated with infants with Turner syndrome: a retrospective study. J Paediatr Child Health. May-Jun 2003;39(4):293-8. [Medline].
Stratakis CA, Rennert OM. Turner Syndrome An Update. The Endocrinologist. 2005;15:27-36.
Zinn AR, Ross JL. Molecular analysis of genes on Xp controlling Turner syndrome and premature ovarian failure (POF). Semin Reprod Med. Jun 2001;19(2):141-6. [Medline].
Further Reading
Keywords
Turner syndrome, Turner's syndrome, 45,X karyotype, Bonnevie-Ullrich syndrome, gonadal dysgenesis, monosomy X, XO syndrome, short stature, Leri-Weill dyschondrosteosis, coarctation of the aorta, aortic dissection, diabetes mellitus, treatment, diagnosis
