Patient professional reference
Turner syndrome can be defined as loss or abnormality of the second X chromosome in at least one cell line in a phenotypic female. In the majority of affected girls, the normal X chromosome is maternal in origin.
Obvious physical stigmata such as neck webbing affect only approximately 20% of girls with Turner syndrome. Many girls with Turner syndrome experience few problems other than short stature and ovarian failure. Short stature or a poor growth rate can be the first manifestation of Turner syndrome.
Turner syndrome should be considered in any girl with short stature or primary amenorrhoea. Almost all affected women are infertile, but some are able to conceive with assisted reproduction.
Turner syndrome is associated with an increased risk of congenital heart defects, congenital lymphoedema, renal malformations, hearing loss (conductive or sensorineural), osteoporosis, obesity, diabetes and an atherogenic lipid profile. Intelligence is usually normal but there may be problems with nonverbal, social and psychomotor skills.
- Turner syndrome occurs in approximately 1 in every 2,000 live female births. The condition is much more common in utero and it has been estimated that 1-2% of all conceptuses are affected, of whom only 1% will survive to term.
- Complete 45,X monosomy accounts for 40-60% of the karyotypes. Most of the remaining karyotypes show a mosaic pattern - eg, 45,X/46,XX, 45,X/46,XiXq, 45,X/46,XY, 45,X/46,XrX.
NB: advanced maternal age is not a risk factor for Turner syndrome.
Clinical features by age include:
- Newborn infants: may be recognised because they are often borderline small for dates, have lymphoedema of the hands and feet and excessive skin at the nape of the neck, and cardiac abnormalities (eg, coarctation of aorta, pulmonary stenosis, aortic stenosis, bicuspid aortic valve).
- Infancy: length usually close to and parallel to the 3rd centile, feeding difficulties with poor weight gain, poor sleeping pattern.
- Preschool: short stature (height velocity usually low or normal), high activity levels, behavioural difficulties with exaggerated fearfulness, recurrent middle ear infections (otitis media with effusion, conductive hearing loss), sensorineural deafness.
- Older children: height gradually falls away from the 3rd centile, gonadal dysgenesis, middle ear disease, obesity, specific learning difficulties, social vulnerability (social problems, immaturity, less social activity), foot problems (eg, toenail involution, cellulitis), renal anomalies.
- Adolescence: impaired pubertal growth spurt (even with oestrogen induction), ovarian failure (absent/incomplete puberty), obesity, hypertension, increased prevalence of immune disorders (eg, autoimmune thyroiditis, coeliac disease, inflammatory bowel disease), specific learning difficulties, social vulnerability, foot problems.
- Adulthood: infertility, obesity, hypertension, aortic dilatation/dissection, autoimmune thyroiditis, osteoporosis, visuospatial difficulties, sensorineural deafness.
- Eyes - epicanthic folds, oblique palpebral fissures, ptosis, squint, nystagmus, cataracts, amblyopia, and hypermetropia.
- Ears - low-set, posteriorly rotated ears, prominent upturned lobules. Deafness may develop secondary to chronic otitis media; sensorineural hearing impairment.
- Mouth - micrognathia, high palate and mandible abnormalities can result in crowding of teeth and malocclusion.
- Neck - short, webbed; low hairline.
- Chest - broad chest, pectus excavatum, inverted, hypoplastic, widely-spaced nipples.
- Joints - cubitus valgus, congenital hip dislocation.
- Hands - short 4th/5th metacarpals, short fingers, forearm and carpal developmental abnormalities; nail hypoplasia, hyperconvex nails, nail-fold oedema.
- Skin lymphoedema - hands, feet, neck (pterygium coli), pigmented naevi, telangiectasias, vitiligo, keloid, seborrhoeic dermatitis; increased body hair with alopecia. There is a risk of keloid formation with surgery.
- Coarctation of the aorta.
- Bicuspid aortic valve; aortic stenosis.
- Aortic aneurysms.
- Mitral valve prolapse.
- Ectopia cordis.
- Hypoplastic left heart.
- Pulmonary stenosis.
- Vascular malformations (including generalised vascular dysplasia, intestinal telangiectasias, haemangiomas, venous ectasias, lymphangiectasia, cystic hygroma and multiple renal arteries).
- Conduction defects, including prolonged QT interval.
- Double collecting system.
- Absent kidney.
- Horseshoe kidneys.
- Silent hydronephrosis.
- Many have fibrotic ovarian streaks at the time of birth. Removal of bilateral streak gonads prior to starting school is recommended in 45,XO/46,XY mosaics.
- Approximately 30% of girls with Turner syndrome have some spontaneous pubertal development.
There is an increased incidence of autoimmune disorders, particularly autoimmune thyroid disease (both Hashimoto's thyroiditis and Graves' disease), coeliac disease, inflammatory bowel disease, alopecia areata and type 1 diabetes mellitus.
- Chromosome analysis: required for diagnosis. A male phenotype excludes the diagnosis, regardless of karyotype. A buccal smear for Barr bodies is now obsolete. Investigation for the presence of Y chromosomal material (using a Y-centromeric probe): patients with 45,X/46,XY mosaicism may have mixed gonadal dysgenesis and are at a high risk for gonadoblastoma.
- Gonadotrophins: LH and FSH may be elevated in untreated patients aged younger than 4 years. Gonadotrophins are later suppressed to normal or near-normal levels, and then increase to menopausal levels after the age of 10 years. LH and FSH levels should be measured before initiating oestrogen replacement therapy.
- TFTs, thyroid antibodies.
- Haemoglobin A1c or fasting glucose level to screen for diabetes mellitus.
- Renal: renal function tests, electrolytes, urine cultures and ultrasound scan of the renal tract.
- ECG, echocardiography, MRI examination of the heart and aorta.
- Bone age: usually normal before adolescence but is then delayed because of oestrogen deficiency. Bone age should be performed before starting growth hormone or oestrogen therapy. Growth hormone is contra-indicated if the epiphyses are fused.
- Bone density in adulthood: osteoporosis is common.
- Virilisation: the presence of virilisation should prompt a thorough search for Y chromosome material and for gonadal, adrenal or midline tumours.
- Hearing tests.
Initial screening is by ultrasound. Turner syndrome can be diagnosed by amniocentesis or chorionic villous sampling which allows karyotyping of the fetus.
- Other causes of short stature and delayed puberty.
- Noonan's syndrome is associated with some of the clinical features of Turner syndrome.
Turner syndrome is obviously a lifelong condition and, although the majority of patients are healthy, they are susceptible to a number of chronic conditions. For this reason, multidisciplinary follow-up is required as an exercise in screening and prevention, as well as treatment where necessary. Cardiac defects are likely to be the most significant associated health problems. The need for long-term surveillance and awareness of associated conditions should be promoted. Regular renal ultrasound, and screening for impaired glucose tolerance and hypertension are recommended.
Problems of most concern to patients may vary with age but the main four concerns revolve around growth, puberty, fertility and general health. Shared care should include:
- Paediatrics and paediatric endocrinology: particular attention should be given to:
- Pubertal development.
- Thyroid function.
- Screening for coeliac disease.
- Prevention of osteoporosis.
- Ophthalmology: screening for amblyopia and other associated eye disorders is recommended.
- Ear, nose and throat: screening for deafness and secretory otitis media is appropriate.
- Dentist: problems with crowding of teeth and malocclusion should be addressed. Antibiotic prophylaxis to prevent subacute bacterial endocarditis is now less likely to be necessary (see the separate article on Prevention of Endocarditis).
- Orthopaedics: regular review is usually unnecessary.
- Cardiology: all patients should have a cardiological evaluation including echocardiography. Some repeat this every five years. Regular imaging every two years has been suggested, as has use of MRI.
- Urology: about 30% of patients have renal anomalies. There is an increased risk of Wilms' tumour. Annual renal function tests and electrolytes, and urine culture are recommended.
- Genetic counselling: it should be emphasised that Turner syndrome is not inherited.
- Psychological support: generally, psychological health is good but educational and social assessments and support may help integration and general well-being. There is some evidence for lower-than-average levels of neuroticism and a tendency to be more extrovert. There are also studies that show increased levels of hyperactivity and inattention. Therefore, regular psychosocial assessment and support, support for families and appropriate support at school are very important.
Growth and puberty
- Short stature is treated in early childhood with growth hormone therapy. Supplemental oestrogen is initiated by adolescence for pubertal development and prevention of osteoporosis.
- Recombinant human growth hormone (rhGH) is licensed for short stature associated with Turner syndrome. Doses of rhGH between 0.3 to 0.375 mg/kg/week increase short-term growth in girls with Turner syndrome by approximately 3 cm in the first year and 2 cm in the second year of treatment.
- Studies have shown that combining very low-dose oestrogen with growth hormone during childhood may improve growth.
- Gonadal failure is treated with combined oestrogen and progestogen (begin at a time appropriate for teenage peers). Low-dose oestrogen is used initially and then progressed to larger doses cycled with progestogen, with ongoing maintainance with the combined oral contraceptive.
- Fertility may be achieved with oocyte donation, and gamete or embryo transplantation.
- The overall prognosis is good.
- Patients are usually shorter than average (even with growth hormone therapy) and almost all are infertile (although assisted fertility may be successful).
- Life expectancy is slightly shorter than average but may be improved by attention to associated health issues - eg, obesity and hypertension.
Further reading and references
McCarthy K, Bondy CA; Turner syndrome in childhood and adolescence. Expert Rev Endocrinol Metab. 20083(6):771-775.
Donaldson MD, Gault EJ, Tan KW, et al; Optimising management in Turner syndrome: from infancy to adult transfer. Arch Dis Child. 2006 Jun91(6):513-20.
Grote FK, Oostdijk W, De Muinck Keizer-Schrama SM, et al; The diagnostic work up of growth failure in secondary health care an evaluation of consensus guidelines. BMC Pediatr. 2008 May 13
Morgan T; Turner syndrome: diagnosis and management. Am Fam Physician. 2007 Aug 176(3):405-10.
Gonzalez L, Witchel SF; The patient with Turner syndrome: puberty and medical management concerns. Fertil Steril. 2012 Oct98(4):780-6. doi: 10.1016/j.fertnstert.2012.07.1104. Epub 2012 Aug 9.
Papp C, Beke A, Mezei G, et al; Prenatal diagnosis of Turner syndrome: report on 69 cases. J Ultrasound Med. 2006 Jun25(6):711-7
Kavoussi SK, Christman GM, Smith YR; Healthcare for adolescents with turner syndrome. J Pediatr Adolesc Gynecol. 2006 Aug19(4):257-65.
Sagodi L, Solyom E, Tamasi K, et al; Prevalence of coeliac disease in Turner syndrome. Orv Hetil. 2006 Jun 25147(25):1185-8.
Ilyas M, Chu C, Ettles D, et al; Evaluation by magnetic resonance imaging of aortic dilatation and coarctation in adult Turner syndrome patients. Clin Endocrinol (Oxf). 2006 Aug65(2):154-7.
Kilic BG, Ergur AT, Ocal G; Depression, levels of anxiety and self-concept in girls with Turner's syndrome. J Pediatr Endocrinol Metab. 2005 Nov18(11):1111-7.
Boman UW, Hanson C, Hjelmquist E, et al; Personality traits in women with Turner syndrome. Scand J Psychol. 2006 Jun47(3):219-23.
Russell HF, Wallis D, Mazzocco MM, et al; Increased Prevalence of ADHD in Turner Syndrome with No Evidence of Imprinting Effects. J Pediatr Psychol. 2006 Mar 8.
Davenport ML; Approach to the patient with Turner syndrome. J Clin Endocrinol Metab. 2010 Apr95(4):1487-95.
Takeda A, Cooper K, Bird A, et al; Recombinant human growth hormone for the treatment of growth disorders in Health Technol Assess. 2010 Sep14(42):1-209, iii-iv.
Baxter L, Bryant J, Cave CB, et al; Recombinant growth hormone for children and adolescents with Turner syndrome. Cochrane Database Syst Rev. 2007 Jan 24(1):CD003887.
Anti-Müllerian hormone (AMH) is a hormonal measure of ovarian reserve.Ovarian reserve is a term used by fertility specialists to estimate a woman’s chances for having a healthy live born baby using...Femelife
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Patient Platform Limited has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.